trelstar and deslorelin

The availability of GnRH agonist implants offers the possibility of a reversible, temporary downregulation of endocrine and germinative testicular function in male dogs and hobs. This review provides an overview of the registered indication, the induction of temporary infertility in healthy, intact, sexually mature male dogs (4.7 and 9.4 mg deslorelin) and hobs (9.4 mg deslorelin) as well as various off-label indications. Off-label use requires strict indications, informed consent from the owner and a lack of licensed medication (safe and optimum effect). Off-label indications in the male dog include sexual-hormone dependant (disturbing) behavior, benign prostatic hyperplasia, small adenomas of the hepatoid glands and alopecia X. Successful use of deslorelin implants for estrus suppression in jils, but also for the treatment of hyperadrenocorticism in ferrets in general have been described. Similarly, hormonal castration can be induced in tomcats and queens. The variable time to onset of effect and its duration (extremely variable in some animals) represent a challenge for breeders. No (sufficient) contraceptive activity was identified in male rabbits and male guinea pigs; however, treatment did successfully suppress the estrus cycle in female individuals of these species, as well as reproductive activity in male and female rats. Regarding the use in birds and reptiles, significant species-specific differences exist with regard to efficacy, time until onset of effect and duration of downregulation. In birds, the implant is efficient to fully suppress egg laying in chicken, Japanese quail and psittacids. In doves, egg laying is only significantly reduced. Successful treatment of reproduction-associated (unwanted) behaviour patterns (feather picking, aggression) has also been described. In some male birds, namely zebrafinch and Japanese quail, the deslorelin implant is suitable to reduce testosterone levels. Successful treatment of hormone-dependent tumours (Sertoli-cell tumorus) in budgerigars has been described as well as the modulation of specific behavior in turkeys and an efficacy in facilitating their keeping (i. e. reduction of aggression). In reptiles, only the successful use of deslorelin in iguana has been demonstrated to date.. Die Verfügbarkeit von GnRH-Agonist-Implantaten bietet die Möglichkeit der reversiblen, temporären Downregulation der endokrinen und germinativen Hodenfunktion bei Rüden und Frettchenrüden. Diese Übersichtsarbeit liefert einen Überblick über die zugelassene Indikation, Erzielung einer vorübergehenden Unfruchtbarkeit bei gesunden, unkastrierten, geschlechtsreifen Rüden (4,7 und 9,4 mg Deslorelin) und Frettchenrüden (9,4 mg Deslorelin) sowie über verschiedene Off-Label-Indikationen. Die Off-Label-Anwendung erfordert eine strenge Indikationsstellung, Besitzeraufklärung und einen Therapienotstand. Off-Label-Indikationen beim Rüden sind sexualhormonabhängiges (störendes) Verhalten, benigne Prostatahyperplasie, Adenome der perinealen Drüsen und Alopezie X. Die Anwendung erfolgt beim Frettchen zur Unterdrückung der Fertilität und des Zyklus, aber auch zur medikamentösen Therapie des Hyperadrenokortizismus. Bei Katze und Kater kann ebenso eine Unterdrückung der Fortpflanzung induziert werden. Problematisch sind hier insbesondere der variable Wirkeintritt und die unterschiedliche, z. T. sehr lange Wirkdauer. Während kein (ausreichend) kontrazeptiver Effekt bei männlichen Kaninchen und Meerschweinchen nachgewiesen wurde, kann das Implantat den Zyklus bei weiblichen Kaninchen und Meerschweinchen sowie die Reproduktion bei Ratten beiderlei Geschlechts unterdrücken. Bei Vögeln und Reptilien bestehen signifikante speziespezifische Unterschiede hinsichtlich Wirksamkeit, Wirkeintritt und Wirkdauer. Ein erfolgreicher Einsatz ist bei Huhn, Japanwachtel und Psittaziden hinsichtlich Verhinderung der Eiablage beschrieben, bei Tauben kommt es nur zur Reduktion der Eiablage. Berichte zum erfolgreichen Einsatz bei reproduktionsassoziierten Verhaltensproblemen (Federpicken, Aggressivität) liegen ebenfalls vor. Bei männlichen Tieren einzelner Vogelspezies (Japanwachtel, Zebrafink) bewirkt das Deslorelin-Implantat eine Reduktion der Testosteronkonzentration. Therapeutisch ist der erfolgreiche Einsatz beim Wellensittich mit hormonproduzierendem Sertoli-Zell-Tumor sowie beim Truthahn zur Verhaltensmodulation und Haltungserleichterung (Reduktion der Aggression) beschrieben. Bei Leguanen unterdrückt das Implantat die Ovaraktivität.

Topics: Animals; Antineoplastic Agents, Hormonal; Bird Diseases; Birds; Contraception; Dog Diseases; Dogs; Drug Implants; Ferrets; Gonadotropin-Releasing Hormone; Male; Testicular Neoplasms; Triptorelin Pamoate; Veterinary Drugs

The use of a gonadotrophin-releasing hormone agonist slow-release implant (GnRH A-SRI) has become increasingly popular as an alternative for surgical contraception in many species. Although these implants have proven to be very effective in some species (eg, ferrets, rats, chicken, psittacines, and iguanas), they have been found less effective in other species (eg, male guinea pigs and rabbits, veiled chameleons, slider turtles, and leopard geckos). This review provides an overview of the available literature on the effects of GnRH A-SRIs in companion exotic animals.

Topics: Animals; Animals, Exotic; Contraception; Contraceptive Agents; Drug Implants; Female; Ferrets; Gonadotropin-Releasing Hormone; Male; Pets; Rabbits; Rats; Triptorelin Pamoate; Veterinary Drugs

This review aimed to summarize the present knowledge about the effects of GnRH agonist slow-release implants (GnRH A-SRI) on fertility and behaviour in male and female dogs and cats with special focus on deslorelin. Following an initial stimulation of gonadotropin and testosterone secretion possibly associated with an improved semen quality, GnRH A-SRI induce long-term depression of fertility in male dogs and cats with, however, a large individual variation in onset and duration of efficacy especially in cats. The GnRH A-SRI furthermore interfere with testosterone-dependent/affected behaviour; a significant positive effect in reducing sexual behaviour and libido, hypersexuality, intermale dominance and excessive territorial urine marking has been described. Rates of improvement of the respective behaviour are comparable to those after surgical castration, making GnRH A-SRI a valuable option to predict castration-related effects on behaviour and to identify animals where surgical castration will not be beneficial. No effect has been seen in reducing aggression towards humans indicating the need for behavioural therapy to control this problem. Effects on spermatogenesis, steroidogenesis and behaviour have by now been shown to be fully reversible. Knowledge in females is more limited, and particularly, the initial induction of a possibly fertile oestrus and individual variation in duration of efficacy remain problems in bitches and queens treated for suppression of fertility. However, long-term suppression of oestrous cycle and fertility seems to be possible with induced effects shown to be reversible including restoration of normal fertility after the end of efficacy/GNRH A-SRI removal.

Topics: Animals; Behavior, Animal; Cats; Contraception; Delayed-Action Preparations; Dogs; Drug Implants; Estrous Cycle; Female; Fertility; Gonadotropin-Releasing Hormone; Male; Spermatogenesis; Triptorelin Pamoate

Deslorelin (Suprelorin®; Virbac) is a gonadotropin-releasing hormone (GnRH) agonist licensed in select countries for the long-term suppression of fertility in adult male dogs and male ferrets. This article summarizes studies investigating the use of deslorelin implants for the long-term suppression of fertility in male and female domestic cats.. Slow-release deslorelin implants have been shown to generate effective, safe and reversible long-term contraception in male and female cats. In pubertal cats, a 4.7 mg deslorelin implant suppressed steroid sex hormones for an average of approximately 20 months (range 15-25 months) in males and an average of approximately 24 months (range 16-37 months) in females. Reversibility has been demonstrated by fertile matings approximately 2 years post-treatment in both male and female adult cats. In prepubertal female cats of approximately 4 months of age, puberty was postponed to an average of approximately 10 months of age (range 6-15 months) by a 4.7 mg deslorelin implant.. The large variability in the duration of suppression of gonadal activity makes the definition of the optimal time for reimplantation quite challenging. In addition, the temporary stimulation phase occurring in the weeks following deslorelin implantation can induce in adult female cats a fertile estrus that needs to be managed to avoid unwanted pregnancy. Longer duration and larger scale controlled field studies implementing blinding, a negative control group and a carefully controlled randomization to each group are needed. Furthermore, the effects of repeated treatment need to be investigated. Finally, the effect of treatment on growth and bone quality of prepubertal cats needs to be assessed. However, the ease of use, long-lasting effects and reversibility of deslorelin implants are strong positive points supporting their use for controlling feline reproduction.

Topics: Animals; Cats; Contraception; Contraceptive Agents; Delayed-Action Preparations; Drug Implants; Female; Fertility; Male; Triptorelin Pamoate

Pre-pubertal gonadectomy in dogs and cats is still controversially discussed because some consequences cause health problems. Nevertheless, postponement of puberty, that is, prevention of an increase in sexual hormones and thereby prevention of their manifold effects, is of major importance, not only in controlling overpopulation but also to preserve the genetic base for future breeding stock and pets. Therefore, alternatives for surgical suppression of fertility in pre-pubertal animals were critically reviewed. As a promising alternative, the slow-release GnRH agonist deslorelin and other GnRH analogues have been investigated. In female dogs and cats, puberty could be significantly postponed without initial flare-up effect and without disturbance of body development. First trials to delay puberty in female and male cats by application of a 4.7-mg deslorelin implant 24 h after birth so far are promising. In female dogs, a previous investigation showed that when the implant was inserted at the age of 4 months, the initial flare-up effect was prevented. Body development was normal in the studies reviewed here, and with the 9.4-mg implant, puberty was significantly delayed until the age of 21 months or older. In one study, bitches either received a 4.7- or a 9.4-mg implant at the age of 4 months and the epiphyses were mostly closed before the time of first oestrus. Using a 4.7-mg deslorelin implant in pre-pubertal male dogs significantly postponed puberty, and age at puberty was >2 years when a 9.4-mg implant was used. However, further investigations are required, especially concerning the effect of different GnRH agonist dosages and resorption rates on the duration of postponement of puberty as well as long-term effects in both dogs and cats.

Topics: Animals; Cats; Dogs; Drug Implants; Enzyme Inhibitors; Female; Male; Sexual Maturation; Triptorelin Pamoate

Over the years, many contraceptive medications have been developed for companion animals, but many secondary adverse effects have limited their use. A major advancement was achieved with the use of gonadotropin-releasing hormone (GnRH) analogues, mainly GnRH agonists, which mimic the effects of native GnRH. The development of effective low-dose, slow-release implants with potent agonists such as deslorelin (Suprelorin®, Virbac) have allowed their use to become widespread in recent years, with many potential benefits in companion animals. While the major application of deslorelin was initially male contraception, due to its two differing actions, either the stimulation of oestrus or the sterilization of fertility, its use has been increasing in the bitch as well. The aim of this study is to review the applications of deslorelin GnRH agonist implants in companion animal, such as dogs, cats and some exotic pets.

Topics: Animals; Cats; Contraceptive Agents; Dogs; Drug Implants; Estrus; Female; Fertility; Gonadotropin-Releasing Hormone; Male; Pets; Triptorelin Pamoate

In 2009 Suprelorin® was released in Switzerland for the temporary suppression of fertility in male dogs. However, in practice it has also been used to treat other conditions in male dogs and in bitches. These include treatment of benign hyperplasia of the prostate, the induction or suppression of oestrus and treatment for the side effects of gonadectomy. Also in feline reproductive medicine GnRH-agonists gain increased importance. These areas of application are listed here in terms of treatment success and possible adverse effects after treatment of which owners have to be informed beforehand.

Topics: Animals; Cat Diseases; Cats; Dog Diseases; Dogs; Enzyme Inhibitors; Estrus; Female; Fertility; Male; Ovariectomy; Prostatic Hyperplasia; Triptorelin Pamoate; Urinary Incontinence

The effects of gonadotrophin-releasing hormone agonist (GnRH-a) administered in the luteal phase remains controversial. This meta-analysis aimed to evaluate the effect of the administration of a single-dose of GnRH-a in the luteal phase on ICSI clinical outcomes.. The research strategy included the online search of databases. Only randomized studies were included. The outcomes analyzed were implantation rate, clinical pregnancy rate (CPR) per transfer and ongoing pregnancy rate. The fixed effects model was used for odds ratio. In all trials, a single dose of GnRH-a was administered at day 5/6 after ICSI procedures.. All cycles presented statistically significantly higher rates of implantation (P<0.0001), CPR per transfer (P=0.006) and ongoing pregnancy (P=0.02) in the group that received luteal-phase GnRH-a administration than in the control group (without luteal-phase-GnRH-a administration). When meta-analysis was carried out only in trials that had used long GnRH-a ovarian stimulation protocol, CPR per transfer (P=0.06) and ongoing pregnancy (P=0.23) rates were not significantly different between the groups, but implantation rate was significant higher (P=0.02) in the group that received luteal-phase-GnRH-a administration. On the other hand, the results from trials that had used GnRH antagonist multi-dose ovarian stimulation protocol showed statistically significantly higher implantation (P=0.0002), CPR per transfer (P=0.04) and ongoing pregnancy rate (P=0.04) in the luteal-phase-GnRH-a administration group. The majority of the results presented heterogeneity.. These findings demonstrate that the luteal-phase single-dose GnRH-a administration can increase implantation rate in all cycles and CPR per transfer and ongoing pregnancy rate in cycles with GnRH antagonist ovarian stimulation protocol. Nevertheless, by considering the heterogeneity between the trials, it seems premature to recommend the use of GnRH-a in the luteal phase. Additional randomized controlled trials are necessary before evidence-based recommendations can be provided.

Topics: Algorithms; Dose-Response Relationship, Drug; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Infertility; Luteal Phase; Ovulation Induction; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Sperm Injections, Intracytoplasmic; Treatment Outcome; Triptorelin Pamoate

GnRH analogues have achieved widespread clinical use for the control of reproduction in animals. Over 2000 analogues of GnRH have been developed and tested over the last 30 years. Paradoxical anti-fertility effects are seen when the more potent agonists are delivered continuously to animals. The evaluation of agonist potency depends largely on the model used and wide varying potencies are reported for the same agonist. The design of analogues has centered on improving the receptor-binding and subsequent activation for agonists. Antagonists have been produced with strong receptor binding but without activation. Deslorelin is classified as a superagonist, with a potency perhaps 100 times that of GnRH. The interactions between agonist potency, dose and duration of treatment largely determine whether pro- or anti-fertility effects are induced. Due to the peptide nature of the synthetic analogues oral administration and potential gastrointestinal enzymatic degradation poor bioavailability results necessitating a parenteral delivery system. Some GnRH antagonists have been associated with significant histamine release, inhibiting their widespread use. More recently, antagonists have been developed that avoid this side effect without compromising potency. However the GnRH antagonist development has lagged behind that of the agonists, in part related to their high cost of production. In conclusion, GnRH agonists have achieved widespread clinical use in animals for controlling reproduction in either pro- or anti-fertility roles, yet antagonist development has been slower.

Topics: Amino Acid Sequence; Animals; Drug Delivery Systems; Drug Evaluation; Gonadotropin-Releasing Hormone; Receptors, LHRH; Structure-Activity Relationship; Triptorelin Pamoate

Pregnancy rate to the Ovsynch protocol can be improved if cows are presynchronized (i.e., two PGF(2alpha) injections given 14 days apart and the second injection of PGF(2alpha) given 12 days prior to the first GnRH of the Ovsynch program) so that a greater proportion of cows during the Ovsynch protocol ovulate to the first GnRH injection and have a CL at PGF(2alpha) injection. Pregnancy rates were normal in anestrous cows (39.6%) if they ovulated to both injections of GnRH. Estradiol cypionate (ECP) can be used to replace GnRH to induce ovulation as a modification of the Presync-Ovsynch program (i.e., Presync-Heatsynch). Pregnancy rates after TI were 37.1+/-5.8% for Presync-Ovsynch compared to 35.1+5.0% for Presync-Heatsynch. Use of ECP to induce ovulation was an alternative to GnRH in which greater uterine tone, ease of insemination and occurrence of estrus, improved acceptance by inseminators. A GnRH agonist (Deslorelin; 750 microg) implant inserted at 48 h after injection of PGF(2alpha), as a component of the Ovsynch protocol, induced ovulation, development of a normal CL and delayed follicular growth until 24 d after implant insertion. Utilization of Deslorelin implants (450 microg and 750 microg) to induce ovulation compared to GnRH (100 microg) within the Ovsynch protocol resulted in 27 d pregnancy rates (GnRH 100 microg, 39%; Deslorelin implants 450 microg, 40% and 750 microg, 27.5%) with 12.7%, 5.0% and 9.5% embryonic losses by 41 d of pregnancy, respectively. Induction of an accessory CL with injection of hCG on day 5 after insemination improved conception rates by 7.1%. Bovine somatotrophin injected at first insemination following a Presync-Ovsynch program in cycling-lactating dairy cows increased 74 days pregnancy rates (57.1%>42.6%).

Topics: Animals; Cattle; Chorionic Gonadotropin; Dinoprost; Drug Implants; Female; Gonadotropin-Releasing Hormone; Growth Hormone; Insemination, Artificial; Ovary; Ovulation Induction; Pregnancy; Reproduction; Triptorelin Pamoate

Topics: Adolescent; Body Mass Index; Child; Epilepsy; Female; Follicle Stimulating Hormone; Follow-Up Studies; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Male; Obesity; Ovary; Puberty, Precocious; Testis; Triptorelin Pamoate

Semen quality, mare status and mare management during estrus will have the greatest impact on pregnancy rates when breeding mares with frozen semen. If semen quality is not optimal, mare selection and reproductive management are crucial in determining the outcome. In addition to mare selection, client communication is a key factor in a frozen semen program. Old maiden mares and problem mares should be monitored for normal cyclicity and all, except young maidens, should have at least a uterine culture and cytology performed. Mares with positive bacterial cultures and cytologies should be treated at least three consecutive days when in estrus with the proper antibiotic. With frozen semen, timing the ovulation is highly desirable in order to reduce the interval between breeding and ovulation. The use of ovulation inducing agents such as human chorionic gonadotropin (hCG) or the GnRH analogue, deslorelin, are critical components to accurately time the insemination with frozen semen. Most hCG treated mares ovulate 48h post-treatment (12-72h) while most deslorelin (Ovuplant) treated mares ovulate 36-42h post-treatment. However, mares bred more than once during the breeding cycle appear to have a slight but consistent increase in pregnancy rate compared to mares bred only once pre- or post-ovulation. In addition, the "capacitation-like" changes inflicted on the sperm during the process of freezing and thawing appear to be responsible for the shorter longevity of cryopreserved sperm. Therefore, breeding closer to ovulation should increase the fertility for most stallions with frozen semen. Recent evidence would suggest that breeding close to the uterotubal junction increases the sperm numbers in the oviduct increasing the chances of pregnancy. Post-breeding examinations aid in determining ovulation and uterine fluid accumulations so that post-breeding therapies can be instituted if needed. Average pregnancy rates per cycle of mares bred with frozen semen are between 30 and 40% with a wide range between sires. Stallion and mare status are major factors in determining the success of frozen semen inseminations. Pregnancy rates are lower for barren and old maiden mares as well as those mares treated for uterine infections during the same cycle of the insemination. To maximize fertility with frozen semen, a careful selection of the stallions and mares, with proper client communication is critical. Dedication and commitment of mare owner and inseminator will have the m

Topics: Animal Husbandry; Animals; Chorionic Gonadotropin; Cryopreservation; Enzyme Inhibitors; Female; Fertility; Gonadotropin-Releasing Hormone; Horses; Insemination, Artificial; Male; Ovulation Induction; Pregnancy; Semen; Semen Preservation; Spermatozoa; Time Factors; Triptorelin Pamoate

Topics: Adult; Age Determination by Skeleton; Age Factors; Body Height; Buserelin; Child; Clinical Trials as Topic; Female; Gonadotropin-Releasing Hormone; Humans; Male; Nafarelin; Prognosis; Puberty, Precocious; Triptorelin Pamoate

There is a need for a safe, effective and practical method of oestrus suppression in the mare. The aim of this study was to monitor ovarian activity in mares exposed to either 9.4 or 28.2 mg deslorelin acetate, a GnRH agonist, in the form of a sustained-release implant. Following oestrus synchronisation, mares were randomly assigned to one of three groups (n = 4 per group) and administered either one (Des1 group; 9.4 mg) or three (Des3 group; 28.2 mg) implants of deslorelin acetate (Suprelorin-12, Virbac Australia) or one blank implant (Control group; Virbac Australia). Mares underwent weekly blood sampling for 12 weeks following implant placement (Day 0-Day 84), with transrectal palpation and ultrasonography of the reproductive tract at all sampling timepoints except Days 56, 70 and 77. All mares showed baseline serum progesterone concentrations (SPC; ≤1.3 nmol/L or 0.4 ng/ml) on Day 0. Cycling Control mares showed typical oestrous cyclicity characterised by peaks and troughs in SPC over time. Four of eight treated mares demonstrated a sustained elevation in SPC after the initial ovulation after implant placement; SPC declined to baseline levels (Des1 group; 2 mares) or remained elevated (Des3 group; 2 mares) at the final sampling timepoint on Day 84. Oestrous cyclicity was erratic in three of the remaining four treated mares. In total, 87.5% (7 of 8) of treated mares showed atypical oestrous cyclicity after implant placement. These results suggest that deslorelin acetate disrupts oestrous cyclicity in the mare, which warrants further research.

Topics: Animals; Delayed-Action Preparations; Female; Gonadotropin-Releasing Hormone; Horses; Ovulation; Periodicity; Triptorelin Pamoate

Approaches to downregulate ovarian function in the sexually mature bitch by applying slow release GnRH agonist implants are hampered by the initial stimulation of folliculogenesis (flare up) and the resulting side effects. The present pilot study was designed to test to what extent these effects can be suppressed by simultaneous treatment with the 3ß-hydroxysteroid-dehydrogenase (HSD3B) blocker trilostane (T). Treatment with T in 6-h intervals completely blocked adrenal cortisol production. However, in parallel and concomitant with the increase of LH, progesterone and estradiol levels increased, ending up in pro-estric steroid levels in two of the three dogs. Hormonal changes were reflected in the respective clinical symptoms. During the whole observation period the course of LH concentrations did not indicate downregulation of pituitary function as a result of treatment with the GnRH-agonist Suprelorin®, 4.7 mg. The incomplete inhibitory effect of T on the follicular production of sex steroids could be explained by an insufficient transfer of T into the follicular compartment or the existence of a HSD3B isoform in the dog ovary different from the adrenal enzyme. Concerning the lack of downregulation and when accounting for published data different pharmacodynamics/pharmacokinetic activities of GnRH-agonists should be taken into account.

Topics: 3-Hydroxysteroid Dehydrogenases; Animals; Dihydrotestosterone; Dogs; Down-Regulation; Drug Implants; Enzyme Inhibitors; Estradiol; Estrous Cycle; Female; Gonadotropin-Releasing Hormone; Hydrocortisone; Luteinizing Hormone; Ovary; Progesterone; Triptorelin Pamoate

Deslorelin 4.7 mg and melatonin 18 mg subcutaneous implants were studied in purebred male and female cats, via questionnaires sent to French cat breeders, to assess breed, age, duration of the contraceptive effect, fertility after use, changes in behaviour and side effects.. Reproductive data were collected in 57 tom cats and 41 queens implanted with deslorelin 4.7 mg, and 42 queens implanted with melatonin 18 mg, for a total of 140 purebred cats, from 38 different catteries, representing 18 breeds.. Using deslorelin (Suprelorin 4.7 mg; Virbac), sexual behaviour in males was inhibited for a mean ± SD of 13.4 ± 3.2 (range 8-21) months in 37/57 cats. Of these, 24/37 mated successfully and produced litters at a mean of 15.5 ± 3.6 (range 9-20) months. Inhibition lasted 11 ± 1.1 (range 9-12; n = 6), 13.2 ± 2.4 (range 12-18; n = 6) and 15 ± 3.5 (range 9-18; n = 6) months in Norwegian Forest Cat, Singapura and Ragdoll males, respectively. In 26/41 females implanted with deslorelin 4.7 mg, oestrus was inhibited for a mean of 16.0 ± 5.7 (8-38) months; 12/26 went on to produce a litter. Of the side effects specific to females: two presented persistent oestrus, leading to the removal of the implant; two developed lactation; one had fibroadenomatosis; and one was sterilised owing to cystic endometrial hyperplasia. Using melatonin (Melovine 18 mg; Ceva), 33/42 females had oestrus inhibited for a mean of 86 ± 50 (range 21-277) days after implantation with a peak return to oestrus in March, and 12/33 had a subsequent litter. No side effects were reported.. This study is the first to collect a large amount of field data, in 140 purebred male and female cats where a deslorelin 4.7 mg or a melatonin 18 mg implant was used. These field results may allow for more accurate clinical advice and open up new avenues of research.

Topics: Animals; Cats; Contraception; Contraceptive Agents; Drug Implants; France; Melatonin; Triptorelin Pamoate

The aim of this study was to compare arterial blood flow determined by repeated Doppler sonographic examinations in the periovulatory period in GnRH-induced and spontaneous estrous cycles of bitches. The study was performed on 10 bitches with GnRH agonist implant-induced estrus (Suprelorin

Topics: Animals; Arteries; Blood Flow Velocity; Dogs; Drug Implants; Estrous Cycle; Female; Gonadotropin-Releasing Hormone; Ovary; Ovulation; Random Allocation; Triptorelin Pamoate; Ultrasonography, Doppler

The objective of the current study was to evaluate the effects of deslorelin and hCG, two ovulation-inducing therapies, on LH surge and follicle vascularity in mares. Thirty mares were either treated with 1.5 mg IM of deslorelin, 2,500 IU IV of hCG or 2 mL IM of NaCl 0.9% (GnRH, hCG and Saline groups, respectively). Power-flow Doppler examination and blood collection were performed every hour during the first 12 hours after treatment (H0) and every six hours between hours 12 (H12) and 30 (H30) after treatment. Moreover, endpoints were evaluated every hour through the last six hours before ovulation (OV-6 to OV-1). In GnRH group, plasma LH concentration progressively increased (P < 0.001) during the first 6 hours after treatment and remained high (P > 0.1) until OV-1. A significant increase in LH concentrations was first detected (P < 0.05) at 24 hours after treatment in hCG group, while no changes (P > 0.1) on LH levels were found during H0-H30 and between OV-6 and OV-1 in the Saline group. Independent of the treatment, significant variations on the percentage of the follicle wall with Doppler signals were not observed (P > 0.1) throughout the entire experiment. A weak correlation between the preovulatory follicle vascularity and the plasma LH concentration was found in GnRH, hCG and Saline groups (r = +0.29, +0.29 and -0.23, respectively; P ˂ 0.0001). These results described for the first time the immediate and continuous pituitary response to ovulation-inducing therapy with injectable deslorelin. Moreover, spontaneous and induced ovulations were not preceded by an increased follicle vascularity, which differs from previous reports in large animals.

Topics: Animals; Chorionic Gonadotropin; Enzyme Inhibitors; Female; Horses; Luteinizing Hormone; Ovarian Follicle; Pituitary Gland; Pregnancy; Triptorelin Pamoate

Antiandrogen, aromatase inhibitor, and gonadotropin-releasing hormone analog (GnRHa) treatment normalizes growth rate and bone maturation and increases predicted adult height (AH) in boys with familial male-limited precocious puberty (FMPP). To evaluate the effect of long-term antiandrogen, aromatase inhibitor, and GnRHa on AH, boys with FMPP who were treated were followed to AH.. Twenty-eight boys with FMPP, referred to the National Institutes of Health, were started on antiandrogen and aromatase inhibitor at 4.9 ± 1.5 years of age; GnRHa was added at 6.9 ± 1.5 years of age. Treatment was discontinued at 12.2 ± 0.5 years of age (bone age, 14.4 ± 1.3). AH was assessed at 16.4 ± 1.3 years of age (bone age, 18.5 ± 0.6).. AH (mean ± SD) for all treated subjects was 173.6 ± 6.8 cm (-0.4 ± 1.0 SD relative to adult US males). For 25 subjects with pretreatment predicted AH, AH significantly exceeded predicted AH at treatment onset (173.8 ± 6.9 vs 164.9 ± 10.7 cm; P < .001), but fell short of predicted AH at treatment discontinuation (177.3 ± 9.0 cm; P < .001). For 11 subjects with maternal or sporadic inheritance, the mean AH was 3.1 cm (0.4 SD score) below sex-adjusted midparental height (175.4 ± 5.8 vs 178.5 ± 3.1 cm [midparental height]; P = .10). For 16 subjects with affected and untreated fathers, AH was significantly greater than fathers' AH (172.8 ± 7.4 vs 168.8 ± 7.2 cm; P < .05).. Long-term treatment with antiandrogen, aromatase inhibitor, and GnRHa in boys with FMPP results in AH modestly below sex-adjusted midparental height and within the range for adult males in the general population.

Topics: Adult; Anastrozole; Androgen Antagonists; Aromatase Inhibitors; Body Height; Child; Child, Preschool; Drug Administration Schedule; Drug Therapy, Combination; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Nitriles; Puberty, Precocious; Spironolactone; Testolactone; Treatment Outcome; Triazoles; Triptorelin Pamoate

Objectives The aim of the study was to evaluate the efficacy of a 4.7 mg deslorelin implant in tom cats. Methods Nine mature male cats were included in the deslorelin group and five cats in the control group. Before the study started, all cats were confirmed to have distinct sexually dimorphic behaviour. Blood samples were taken on the implantation day, at day 7 and at day 15, then monthly, in order to measure serum dihydrotestosterone (DHT) and 17beta(β)-oestradiol concentrations. The deslorelin group (n = 9) was divided into two subgroups: five cats (cats 1-5) were neutered in the postimplantation period during suppression of sexually dimorphic behaviour, and four cats (cats 6-9) were neutered after re-expression of sexually dimorphic behaviour. The control group cats (n = 5) were castrated without administration of the implant. Results Sexually dimorphic behaviours ceased within a mean ± SD of 13-58 days (23.30 ± 14.17) after implantation. DHT concentration decreased within 30 days. The mean duration of suppression was 26.5 ± 7.42 months and reactivation coincided with increased DHT values reaching preimplantation concentrations within 1 month. 17β-oestradiol concentrations significantly correlated with DHT concentrations ( P <0.01). For cats castrated during suppression of sexual behaviour, the length of the long axes of the nuclei of Leydig cells, the diameter of seminiferous tubules and the height of the epithelium of the seminiferous tubules did not change until 3-6 months after implantation, whereas at 12 and 32 months the measured values were even lower than in the control group. For cats castrasted after reactivation, the length of long axes of the nuclei of Leydig cells and the diameter of seminiferous tubules approached the values of the control group between 4 and 6 months after reactivation. Conclusions and relevance A deslorelin implant (4.7 mg) suppresses sexually dimorphic behaviour in tom cats without any side effects and with full reversibility; however, duration of suppression is highly individual.

Topics: Animals; Cats; Dihydrotestosterone; Drug Implants; Enzyme Inhibitors; Estradiol; Gonadotropin-Releasing Hormone; Male; Sexual Behavior, Animal; Testis; Treatment Outcome; Triptorelin Pamoate

This study was conducted to investigate the effect of GnRH-agonist implantation in prepubertal tomcats on sexual behavior, reproductive performance, and expression of testicular LH receptor (LHR) and FSH receptor (FSHR) and also to compare the testicular characteristics, LHR and FSHR expression between prepubertal and adult tomcats. In experiment 1, 3-month-old tomcats (n = 6/group) were either treated with or left without 4.7 mg deslorelin implants. Semen collection and evaluation were performed just before castration at 48 weeks after treatment; removed testes were analyzed for mRNA and protein expression of LHR and FSHR. We were able to collect semen from six non-treated cats, whereas in treated cats, semen was uncollectable. The results revealed that sexual behavior was absent in the implanted cats throughout the study period. Testicular volume was found to decrease from 30 weeks after treatment onward in the implanted cats compared to the controls (P < 0.05). Semen production was found only in non-implanted cats. Testicular tissue score, seminiferous tubule diameter, and LHR protein expression were found lower in the implanted cats (P < 0.05), but no differences were observed in mRNA expression of LHR and protein expression of FSHR between groups. The mRNA expression of FSHR was higher in the implanted (P < 0.05) compared to control cats. In experiment 2, testes from prepubertal (n = 6) and adult (n = 6) male cats were collected after castration and analyzed for mRNA and protein expression of LHR and FSHR. No differences were observed in the protein expression of LHR and FSHR between the two groups, whereas mRNA expression of FSHR was higher in prepubertal cats (P < 0.05). Testicular and epididymal weight, diameter of seminiferous tubules, and the testicular grade were higher in the adult compared to prepubertal cats (P < 0.05). In conclusion, deslorelin implants suppressed protein expression of LHR and enhanced mRNA expression of FSHR along with suppression of reproductive function without any adverse effects for at least 48 weeks in male cats.

Topics: Animals; Cats; Contraception; Drug Implants; Gene Expression; Gonadotropin-Releasing Hormone; Male; Population Control; Receptors, FSH; Receptors, LH; Reproduction; Sexual Maturation; Testis; Triptorelin Pamoate

To investigate the comparative efficacy of BioRelease Deslorelin® (BRD) and Ovuplant® for induction of ovulation in cyclic mares in Australia.. Ovarian follicular activity of 60 mares for a total of 95 cycles was monitored by ultrasonography until they developed a follicle ≥30 mm and a uterine oedema pattern of 3. Mares were then randomly allocated to one of three treatment groups: (1) treatment with 1.25 mg BRD, (2) a single Ovuplant pellet or (3) 1 mL compound sodium lactate control. Follicular activity was monitored with ultrasonography every 12 h until ovulation was detected or for at least 5 days post treatment. The injection site on each mare was monitored for reaction for a minimum of 5 days post treatment.. There was no difference in the percentage of mares ovulating within 48 h when treated with BRD (93.75%) compared with Ovuplant (87.09%). Treatment with both ovulating agents significantly decreased the time to ovulation compared with control mares (P < 0.00005). More mares had injection site reactions with Ovuplant (64.5%) treatment compared with BRD (15.6%) or control mares (0%) (P < 0.00005).. Treatment of mares with 1.25 mg BRD when there is a follicle ≥30 mm and uterine oedema pattern of 3 is as effective as treatment with Ovuplant.

Topics: Animals; Drug Implants; Enzyme Inhibitors; Estrus; Female; Horses; Injections, Intramuscular; Linear Models; Ovulation; Ovulation Induction; Triptorelin Pamoate; Ultrasonography

Reproductive disease in captive avian species is common, and medical management is often chosen over surgical removal of the reproductive tract. In a previous study with Japanese quail, a single 4.7-mg deslorelin acetate implant reversibly decreased egg production in 6 out 10 birds for 70 days. The objective of the current study was to evaluate the effects of two 4.7-mg deslorelin acetate implants versus one 9.4-mg implant on egg production and plasma progesterone concentrations in Japanese quail ( Coturnix coturnix japonica). Following a 10-day period of consistent egg laying, 30 adult female Japanese quail were anesthetized and received two 4.7-mg deslorelin implants (n = 10), one 9.4-mg deslorelin implant (n = 10), or a single, identical placebo implant (n = 10) s.c. between the scapulae. Egg production was monitored daily, and plasma progesterone concentrations were measured on days 0, 14, 29, 120, 148, and 182 via enzyme-linked immunoassay. All birds were weighed periodically and euthanized at day 182, after which their reproductive tracts were evaluated at gross necropsy. Seven out of 10 birds treated with two 4.7-mg implants ceased egg laying 1 wk after implantation and remained nonovulatory for approximately 100 days. Cessation of egg laying for the 9.4-mg treatment group occurred in 7 out of 10 birds; onset was variable (weeks 5-12) and continued for the remainder of the study period. Plasma progesterone concentrations for deslorelin treatment groups were not significantly different compared to the placebo group at any time point. In conclusion, the two 4.7-mg and the one 9.4-mg implant treatments ceased egg laying in a similar number of birds, but the 9.4-mg implant had a slower onset of action and the effects on egg laying were inconsistent throughout the study period. Further studies evaluating use of deslorelin acetate in other avian species are needed.

Topics: Animals; Coturnix; Drug Implants; Enzyme Inhibitors; Female; Oviposition; Progesterone; Triptorelin Pamoate

This randomized, multicenter, open-label clinical trial was intended to generate pilot data on the efficacy and safety of the gonadotropin-releasing hormone agonist (GnRHa) deslorelin (D) with low-dose estradiol ± testosterone (E2  ± T) add-back for endometriosis-related pelvic pain.. Women with pelvic pain and laparoscopically confirmed endometriosis were treated with a six-month course of daily intranasal D with concurrent administration of either transdermal E2, intranasal E2, or intranasal E2  + T. Efficacy data included evaluation of dyspareunia, dysmenorrhea, pelvic pain, tenderness, and induration. Cognition and quality of life were also assessed. Safety parameters included assessment of endometrial hyperplasia, bone mineral density (BMD), and hot flashes.. Endometriosis symptoms and signs scores decreased in all treatment arms from a baseline average of 7.4 to 2.5 after 3 months of treatment and 3.4 after 6 months. BMD changes and incidence of hot flashes were minimal, and no endometrial hyperplasia was observed. Patient-reported outcomes showed significant improvement across multiple domains.. Daily intranasal D with low dose E2  ± T add-back resulted in significant reduction in severity of endometriosis symptoms and signs with few safety signals and minimal hypoestrogenic symptoms that would be expected with the use of a GnRHa alone.

Topics: Adult; Endometriosis; Enzyme Inhibitors; Estradiol; Female; Humans; Middle Aged; Testosterone; Triptorelin Pamoate

Deslorelin acetate is a GnRH agonist used for contraception in dogs. This study aimed to evaluate the treatment of pre-pubertal female dogs with deslorelin acetate implants, to better investigate the primary stimulatory effect of the drug and the long-term effects on the genital tract, throughout repeated treatments. Sicilian hound female dogs (24) were randomly assigned to treated group, control group 1 and control group 2. First group bitches were implanted at 4.5, 9.0 and 13.5 months and monitored clinically, ultrasonographically and endocrinologically, throughout the study period (13.5 months). Control group 1 bitches were not implanted and clinically monitored for the same period. At 18 months, the animals underwent ovariohysterectomy, thus allowing evaluation of the internal genitalia. Control group 2 bitches were ovariohysterectomized at the age of 4.5 months. The suppression of oestrus was obtained in the treated group despite the fact that the first implant caused a modest increase in plasmatic levels of 17-beta estradiol and an evident cornification of the vaginal mucosa cells (50-80%). Estradiol and progesterone were at baseline levels for the remaining study period, in which no other oestrous manifestations were observed. The external genitalia maintained a juvenile appearance. The ovaries, ultrasonographically, showed no follicular structures and stayed the same size. At 18 months, the genital tract was still juvenile with inactive small ovaries and a thin filiform uterus. Deslorelin suppressed ovarian activity in pre-pubertal bitches, and oestrous induction was not observed despite the presence of the primary stimulatory effect of the drug. Juvenile genitalia were an expected side effect of the treatment.

Topics: Animals; Contraceptive Agents, Female; Dogs; Drug Implants; Enzyme Inhibitors; Female; Sexual Maturation; Triptorelin Pamoate

The aim of this study was to reproductively assess the clinical and hormonal effects of a GnRH agonist (AG) and an antagonist (AN) administered during the postnatal period in domestic cats. Forty-eight male and female postnatal kittens were randomly assigned to deslorelin acetate 1.6 mg subcutaneous (AG; n = 16), acyline 33 μg/100 g subcutaneous weekly for 3 months (AN; n = 16), or control (CO; n = 16) which remained untreated. The cats were followed up (behavioral observation, physical examination, fecal sexual steroid determinations, mating test, and pregnancy diagnosis) up to puberty. Puberty was delayed (weeks) in the AG animals (62.9 ± 3.5; P < 0.01) but not in the AN (15.5 ± 1.7; P > 0.05) when they were compared with CO kittens (13.4 ± 0.4). Fifteen (15/16) of the AN and CO animals, and only 11 of 16 cats of the AG group were fertile (P > 0.1). No differences were found in body weight (P > 0.1) and measurements (P > 0.1), libido (P > 0.1) and in the appearance of side effects (P > 0.1; except a pyometra in an AG female) among groups. In both AG- and AN-treated males (testosterone; P < 0.01) and females (estradiol-17β; P < 0.01) fecal hormone concentrations were lower than in CO group during the first five postnatal weeks but not later. It is concluded that the neonatal administration of these AG and AN decreased fecal sexual steroids during the first postnatal weeks causing, the agonists but not the antagonist, a significant, reversible delay in puberty appearance.

Topics: Animals; Behavior, Animal; Body Weight; Cats; Contraception; Female; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Male; Oligopeptides; Sexual Maturation; Time Factors; Triptorelin Pamoate

In the current study, the duration of effectiveness, owner satisfaction and side effects of a gonadotrophin releasing hormone-agonist (deslorelin) implant were investigated during a two-year follow-up study in which 61 male and 69 female entire pet ferrets were given a 4.7 mg deslorelin implant as alternative to surgical neutering. In 27 participating non-oestrous jills, a double-blind placebo controlled study was performed to investigate whether a single low dose of medroxyprogesterone (2 mg orally) four days preceding placement of the implant could prevent oestrus induction. The duration of effectiveness of the implant ranged from 301 days to over 1339 days (mean 1012±38 days), with no sex difference present. Over 90 per cent of owners were pleased with the effects of the implant. Minor local side effects were noted in less than 20 per cent of ferrets, which all resolved within a week without treatment. Oestrus was induced in 77 per cent of jills receiving medroxyprogesterone and 50 per cent of jills receiving the placebo, indicating that administration of a low-dose progestogen cannot prevent postimplant oestrus. Based on the minimum duration of effectiveness, it is advised to place a new implant on a yearly basis to guarantee continuous gonadal suppression, although biannual replacement may be sufficient in the majority of ferrets.

Topics: Animals; Castration; Double-Blind Method; Drug Implants; Female; Ferrets; Follow-Up Studies; Gonadotropin-Releasing Hormone; Male; Patient Satisfaction; Treatment Outcome; Triptorelin Pamoate

To date, there has been limited research on manipulation of the estrous cycle in endangered equids. The objectives of this study were to assess the efficacy of using combinations of: (a) oral altrenogest and PGF2α, and (b) injectable altrenogest and PGF2α for manipulation of ovarian activity in Przewalski's mares. Reproductive cycles were monitored by assessing follicular changes with rectal ultrasound and changes in urinary steroid hormones. In Study 1, five cycling mares were treated with oral altrenogest (n=11 cycles) for 14 days. In Study 2, cycling mares were treated with oral altrenogest for 12 days (n=5 cycles; n=5 mares) or a single injection of biorelease altrenogest (n=10 cycles; n=6 mares). In all study groups, PGF2α was given 2 days before cessation of progestagen treatment. In Study 1, mares responded in six of 11 cycles (54%) where treatment occurred with normal ovarian follicular development post hormone therapy. In Study 2, mares responded in four of five (80%, oral altrenogest) and eight of 10 (80%, injectable altrenogest) cycles with the development of an ovulatory follicle. With the use of injectable altrenogest, there was an obvious suppression of urinary estrogens and progetsagens. These results indicate that manipulation of the estrous cycle of Przewalski's mares can be achieved by administering oral (12 days) or injectable form of altrenogest in conjunction with PGF2α. Findings in the present study may have long term application for the development of timed artificial insemination as a genetic management tool for this critically endangered equid.

Topics: Administration, Oral; Animals; Dinoprost; Estrogens; Estrous Cycle; Female; Horses; Injections, Intramuscular; Ovarian Follicle; Progestins; Time Factors; Trenbolone Acetate; Triptorelin Pamoate

Hair cycle arrest (alopecia X) refers to a canine alopecic condition of unknown pathogenesis, characterized by symmetrical, nonpruritic and noninflammatory alopecia that spares the head and distal extremities.. The objective of this study was prospectively to evaluate the efficacy of a 4.7 mg deslorelin implant in the treatment of intact male and neutered female dogs affected by hair cycle arrest.. Ten Pomeranian dogs (eight intact males, two neutered females), four Italian spitz (three intact males, one neutered female), three miniature poodles (two intact males, one neutered female), two Siberian huskies (both intact males) and one intact male chow chow dog with confirmed hair cycle arrest were included in the study.. Each dog was treated with a subcutaneous sterile implant containing 4.7 mg deslorelin. Responder dogs were re-implanted 6 months after the first implant in order to obtain a 1 year pharmacological exposure and 1 year of follow-up.. Hair regrowth was visible within 3 months in 12 of 16 intact male dogs (75%); no hair regrowth was noted in any neutered female dogs. The overall response to therapy was 60%. No adverse effects were noted.. These findings suggest that deslorelin may be a treatment option for intact male dogs with idiopathic hair cycle arrest. Deslorelin is an alternative to current therapies and castration.

Topics: Alopecia; Animals; Dog Diseases; Dogs; Drug Delivery Systems; Enzyme Inhibitors; Female; Follow-Up Studies; Male; Prospective Studies; Treatment Outcome; Triptorelin Pamoate

Veterinary practitioners frequently encounter disorders of the reproductive system in avian patients. Management of these disorders relies on manipulating reproduction by modifying the environment, diet, and social interactions, and by the use of pharmacologic agents and surgery, with varying levels of success and side effects. An alternative is to use the gonadotropin-releasing hormone (GnRH) agonist deslorelin to suppress the pituitary-gonadal axis. To determine the efficacy of deslorelin in domestic pigeons (Columba livia), male (n = 10) and female (n = 10) birds each were implanted intramuscularly with a single long-acting implant containing 4.7 mg deslorelin. Untreated males (n = 11) and females (n = 10) were used as controls. The baseline serum concentration of luteinizing hormone (LH) was assayed at 7, 28, 56, and 84 days after treatment, and egg production was recorded weekly. In females, deslorelin administration significantly reduced serum LH concentrations compared to pretreatment levels at 7, 28, 56, and 84 days (P < .05). In males, deslorelin significantly reduced LH concentrations at 7, 28, and 56 days (P < .05). Female birds treated with deslorelin laid significantly fewer eggs over the course of the study (mean = 1.46, SEM = 0.84) compared with controls (mean = 5.54, SEM = 0.88). Deslorelin treatment had no discernible effect on body weight. Deslorelin is effective for controlling egg laying in female pigeons for at least 49 days, but further research is required to determine the effects on male fertility and the duration of action in both sexes.

Topics: Animals; Columbidae; Contraceptive Agents, Female; Contraceptive Agents, Male; Enzyme Inhibitors; Female; Male; Oviposition; Reproduction; Triptorelin Pamoate

Testicular function in the dog was down-regulated using two different GNRH agonist implants, with adult and juvenile testes serving as controls. Treatment resulted in an increased percentage of the interstitial area and decreased area of Leydig cell nuclei. Expression of StAR and the steroidogenic enzymes cytochrome P450 side-chain cleavage enzyme (P450scc, CYP11A1) and cytochrome P450 17α-hydroxylase-17,20-lyase (P450c17, CYP17A1) in Leydig cells was blocked at the mRNA and protein level, showing no differences between the two agonists. Staining for androgen receptor (AR) by immunohistochemistry was positive in Sertoli, Leydig and peritubular cells and some spermatogonia, with in situ hybridization confirming expression in Sertoli cells. At the mRNA level, expression of AR was not affected; however, translation was blocked (reduced percentage of AR-positive Sertoli cells), with the number of nuclei in basal position being decreased. In the juvenile testes, mRNA expression of StAR, CYP11A1 and CYP17A1 was higher compared with the other groups but distinctly lower for the AR. At the protein level, the expression was at the limit of detection for StAR; AR-positive Sertoli cells were not detected. Our observations show that the down-regulated testis is different from the juvenile one rather resembling the testicular status in seasonal breeders out of season.

Topics: Age Factors; Animals; Dogs; Down-Regulation; Drug Implants; Gonadotropin-Releasing Hormone; Leydig Cells; Male; Organ Size; Receptors, Androgen; Sertoli Cells; Spermatogonia; Testis; Triptorelin Pamoate

Coyotes (Canis latrans) are predators of livestock. Current management programs, primarily lethal control, are ineffective for long-term management of predation. Controlling reproduction of coyotes may reduce depredations if territory fidelity is maintained by breeding pairs. Surgical sterilization is successful in altering predatory behaviors of coyotes but may provide a challenge for field implementation. An alternative approach is the development of a one-time non-transferable chemical contraceptive. This research is investigating the efficacy of a single high dose treatment of a sustained release gonadotropin-releasing hormone agonist, deslorelin, on coyotes as a long term contraceptive. Male coyotes were administered 47 mg deslorelin subcutaneously. Preliminary data show full suppression of the reproductive axis for over 12 mo as indicated by complete absence of sperm.

Topics: Animals; Contraception; Contraceptive Agents, Male; Coyotes; Drug Implants; Male; Population Control; Seasons; Testosterone; Time Factors; Triptorelin Pamoate

The present study reports on attempts to delay puberty in a model marsupial species using the gonadotrophin-releasing hormone (GnRH) agonist deslorelin. Female tammar wallaby pouch young received deslorelin (5 mg) or placebo implants (n=8/group) when they were 193±2 days old. Sexual maturity was significantly delayed in deslorelin-treated animals, with the first successful production of offspring in treated and control animals occurring at 813±62 and 430±42 days of age, respectively. This delay was associated with a period of retarded pouch and teat development. Progesterone concentrations remained at basal levels throughout the first breeding season, indicating the absence of luteal cycles in treated females. Recovery and maturation of the hypothalamic-pituitary axis was a gradual process. Treated animals failed to respond to GnRH challenge at 12 months of age and had a reduced LH response at 18 months of age, before attaining full responsiveness by 24 months of age. Despite this apparent pituitary recovery by 24 months of age, as evidenced by complete teat eversion and LH responsiveness to GnRH, the time to first parturition was significantly delayed beyond this time in three females. This suggests that there may be longer-lasting effects at the level of the ovary and/or on FSH secretion. The significant delay in the onset of sexual maturation in response to chronic GnRH agonist treatment in this model marsupial species may be of practical significance to the management of fertility in captive and semi-free range marsupial populations.

Topics: Animals; Bone Development; Contraception; Contraceptive Agents, Female; Drug Implants; Female; Fertility; Gonadotropin-Releasing Hormone; Hypothalamo-Hypophyseal System; Luteinizing Hormone; Macropodidae; New South Wales; Ovary; Pest Control; Progesterone; Random Allocation; Sexual Maturation; Triptorelin Pamoate

To evaluate the effects of 4.7-mg deslorelin acetate implants on egg production and plasma concentrations of 17β-estradiol and androstenedione in Japanese quail (Coturnix coturnix japonica) over 180 days and assess safety of the implants in quail via gross and histologic examination.. 20 female Japanese quail.. Following a 7-day period of consistent egg laying, quail were anesthetized and received a 4.7-mg deslorelin implant (treatment group; n = 10) or identical placebo implant (control group; 10) SC between the scapulae. Egg production was monitored daily. Plasma concentrations of 17β-estradiol and androstenedione were measured on days 0 (immediately prior to implant injection), 14, 29, 62, 90, 120, 150, and 180 via radioimmunoassay. Birds were weighed periodically and euthanized at day 180 for complete necropsy.. Egg production was significantly decreased in the treatment group, compared with the control group, from 2 to 12 weeks after implant injection. Egg production ceased in 6 of 10 quail in the treatment group (mean duration of cessation, 70 days). Plasma androstenedione and 17β　-estradiol concentrations were significantly lower on day 29 in the treatment group than in the control group. On day 180, 17β　-estradiol concentration was lower in control than in treated birds.No clinically relevant lesions were detected in either group at necropsy [corrected].. 4.7-mg deslorelin acetate implants reversibly decreased egg laying for approximately 70 days in most of the Japanese quail evaluated. Further studies evaluating implants containing different concentrations of the drug are needed in quail and other avian species.

Topics: Absorbable Implants; Androstenedione; Animals; Contraceptive Agents, Female; Coturnix; Estradiol; Female; Gonadotropin-Releasing Hormone; Ovum; Radioimmunoassay; Triptorelin Pamoate

The aim of this study was to assess the efficacy and safety of deslorelin acetate implants on domestic queen puberty postponement. Thirty, 114.4 ± 12.7 days old, 1.5 ± 0.1 kg prepubertal crossbred female cats were included in this study. The animals were kept under a positive photoperiod and randomly assigned to deslorelin acetate 4.7 mg SC implants (n = 15) or to a non-treated control group (n = 15). The queens were followed up daily and weighed weekly until puberty. Vaginal cytology was also carried out three times a week. Puberty was diagnosed by the presence of the typical oestrous behaviour and vaginal cytology findings. At puberty, ovariectomy was performed and the gonads grossly described. Age (281.2 ± 21.6 vs 177.8 ± 10.8; p < 0.01) but not weight (2.6 ± 0.1 vs 2.5 ± 0.1; p > 0.1) at puberty differed between the deslorelin and control groups, respectively. One deslorelin-treated female showed an oestrous response and another showed clinical signs of pyometra after the implants. Deslorelin-treated ovaries appeared small, while control gonads were normal. It was concluded that long-term-release deslorelin, administered at approximately 50% adult body weight, postponed feline puberty without altering growing rate.

Topics: Animals; Cats; Delayed-Action Preparations; Drug Implants; Enzyme Inhibitors; Female; Gonadotropin-Releasing Hormone; Sexual Maturation; Triptorelin Pamoate

The objective was to evaluate ovarian activity reversibility in domestic queens after short-term contraceptive treatment with deslorelin acetate. Ten mature queens were used. In all queens, the estrous cycle was evaluated every 72 h by vaginal cytology (VC) and behavior assessments. When queens had VC characteristic of interestrus or diestrus, one deslorelin acetate implant (4.7 mg) was placed in the subcutaneous tissue of the interscapular region (day of insertion = Day 0). Thereafter, VC was performed every 48 h and on Day 90, implants were removed. At Day 100, estrus and ovulation were induced with 100 IU eCG (im), followed by 100 IU hCG (im), 84 h later (Day 103.5). Queens were ovariohysterectomized on Day 106. Corpora lutea (CL) were counted, oviducts were flushed, and oocytes were identified, isolated and stained to assess viability. In all queens, blood samples for plasma progesterone concentrations were collected once a week, from Days -21 to 106. After deslorelin acetate application, four queens had VC and behavior typical of estrus, and one ovulated. Furthermore, ovulation occurred in three queens that did not have VC or behavior consistent with estrus. After the initial ovarian stimulation, all females had anestrous VC during the deslorelin treatment period. Implants were readily removed. Following implant removal, all females responded to treatments to induce estrus and ovulation. There were (mean ± SEM) 13.1 ± 5.5 CL and 8.1 ± 5.5 oocytes per queen; the oocyte recovery rate was 56.8 ± 25.4% and all recovered oocytes were viable. We concluded that deslorelin acetate can be used as a reversible short-term contraceptive in domestic cats, because estrus and ovulation were successfully induced following implant removal.

Topics: Administration, Cutaneous; Animals; Animals, Domestic; Cats; Contraception; Contraceptive Agents, Female; Drug Administration Schedule; Drug Implants; Female; Injections, Intramuscular; Ovary; Recovery of Function; Time Factors; Triptorelin Pamoate; Withholding Treatment

The aim of the study was to assess the efficacy of using a Gn-RH agonist implant (deslorelin, 4.7 mg, Suprelorin) to control sexual activity of male cats and reestablishment of sexual function after the implant removal 4 mo after placement. Using a control group (Group 1, n = 5), 22 domestic tomcats were given the implant subcutaneously in the region of the right shoulder blade and were then divided into two treatment groups. Animals in Group 2 (n = 14) were observed from the date of implant surgery and the observation lasted for 4 mo. In Group 3 (n = 8) all animals were monitored from the date of implant surgery. Then, after 4 mo, all implants were removed and the toms were observed for a further 4 mo. In all animals during their first visit and then in 1-mo intervals, changes in testosterone concentrations were assessed before (T0) and 4 h after (T4) human chorionic gonadotropin (HCG) administration and testis size was measured. In all tomcats, semen collection was performed, using an electroejaculator, in the course of the first visit and then in 2-mo intervals or at the end of observation. Total sperm count was determined in each semen sample. Two to four animals were castrated at weeks 4, 8, 12, 16, 20, 24, 28 and 32 and histologic assessment of the testes was performed. By evaluation of 200 cross sections of seminiferous tubules, the degree of spermatogenic suppression was assessed and animals in Groups 2 and 3 were assigned into groups according to most tubules with the most developed germ cell observed: G1, spermatocytes; G2, round spermatids; G3, elongating spermatids and G4, elongated spermatids. The mean area of Leydig-cell nuclei was calculated. In animals in Group 2, suppression after implant insertion was monitored. T4 concentrations, testis size, and total sperm count gradually decreased (P < 0.01; P < 0.01; and P < 0.05, respectively) within 4 mo after implantation. Histologic evaluation showed a high individual variation in the degree of suppression of spermatogenesis. In animals in Group 3, the implant was removed 4 mo after insertion and the return of sexual activity was monitored. Within 4 mo, T4 concentration and total sperm count increased to the physiological values of intact toms. Testes gradually increased in size and within 4 mo of implant removal almost reached pretreatment size. According to histologic evaluation of the seminiferous tubules, as early as 1 mo after implant removal, all animals were assigned to G4, with most tubu

Topics: Animals; Cats; Contraception; Contraceptive Agents, Male; Down-Regulation; Drug Implants; Ejaculation; Male; Organ Size; Osmolar Concentration; Recovery of Function; Sexual Behavior, Animal; Testis; Testosterone; Triptorelin Pamoate; Withholding Treatment

This study aimed to determine whether deslorelin acetate could induce double ovulation in mares. In Experiment 1, eight mares were treated with prostaglandin on Day 8 (D8) after ovulation, then treated with saline or with 100 μg of a controlled-release formulation of deslorelin acetate vehicle intramuscularly (IM) every 12h from D8 after ovulation until at least two follicles reached 33 mm. At this time, ovulation was induced with 2500 IU of hCG. Artificial insemination was performed 24h after induction, and embryos were collected on the eighth day after ovulation was first detected. In Experiment 2, 112 estrous cycles in 56 mares were studied. In this experiment, the deslorelin acetate protocol was initiated only in mares that achieved a follicle with a diameter of at least 25 mm and at least one second follicle with a diameter≥20mm was detected, at which time 100 μg deslorelin acetate or saline was administered IM every 12h. The other procedures were similar to those described in Experiment 1. The variables studied were analyzed using Student's t-test and Fisher's exact test. In Experiment 1, only two mares in deslorelin group having second follicles of 20-25 mm on responded with double ovulation. In the second experiment, 82% of treated mares responded with double ovulation, and the embryo recovery per estrous cycle was 1.12 and 0.57 in the group treated with deslorelin acetate and the control group, respectively (P<0.05). Deslorelin acetate is effective in inducing double ovulation in mares using the protocol proposed. On average, it allows for the recovery of one embryo by uterine flushing.

Topics: Animals; Embryo Transfer; Enzyme Inhibitors; Female; Horses; Ovarian Follicle; Ovulation; Ovulation Induction; Triptorelin Pamoate

During the last ten years, numerous species have been treated with deslorelin implants to induce contraception. The aims of the study were 1) to assess contraceptive efficacy of 4.7 mg subcutaneous deslorelin implants in rats, 2) to determine the latency of contraceptive effect, and 3) to determine potential side effects. Three experimental females were implanted and their estrous cycle was studied by vaginal smear. Two weeks after implantation, a male whose fertility was previously assessed with a control female, was introduced into their cage. No female conceived during the 4 mo following implantation. Additionally, 38 pet rats were recruited from clients in practice to test for potential side effects, including 6 males and 32 females with a mean age of 14 mo. Local reaction and transient weight gain during the first 2 wk, as well as behavioral changes were recorded. According to this pilot study, deslorelin implant could be used as a contraceptive method in female rats. The latency period is about 2 wk. Nevertheless, it might be possible to refine the treatment further using hormonal measurements. The duration of contraceptive effect is to be determined in an upcoming study.

Topics: Animals; Contraceptive Agents; Drug Implants; Estrous Cycle; Female; Male; Pregnancy; Rats; Triptorelin Pamoate

Four German Shorthair Pointer bitches each produced from two to five (total of 14) purebred litters in response to natural matings to either natural oestrus (n = 8) or oestrus induced by Ovuplant(®), a sustained-release implant containing 2.1 mg deslorelin (n = 6). All bitches initially produced litters from natural oestrous matings prior to producing litters from induced oestrus, and two of the bitches also produced natural litters subsequent to their Ovuplant(®) litters. Mean litter size was lower for Ovuplant(®) litters (5.4 vs 8.6 puppies; p < 0.001) and within each bitch every induced litter was smaller than any of her natural litters.

Topics: Animals; Dogs; Estrus; Female; Fertility Agents; Litter Size; Pregnancy; Pregnancy, Animal; Triptorelin Pamoate

The purpose of this study was to define (i) the interval between treatment and sterility, and (ii) semen quality in male dogs administered a 4.7-mg deslorelin implant. Six healthy, adult dogs of various breeds and body weights were implanted with deslorelin (Suprelorin, Virbac) and followed every 2 weeks with semen and blood collections. Semen quality remained stable or even improved during the first month following treatment and then showed a progressive decline until the end of the study, except for sperm morphology, which was unaffected by the treatment. Complete sterility was achieved on post-treatment days 70, 84, 60, 23, 51 and 40 for dogs 1 to 6, respectively. The 4.7 mg deslorelin implant caused a significant (p < 0.05) decrease in serum testosterone as well as sperm motility. Our results (i) confirm the efficacy of deslorelin in causing reversible sterility in male dogs, (ii) confirm and provide details about endocrine and seminal parameters involved in this process and (iii) contribute to define the interval between treatment and achievement of complete sterility. Practitioners should be aware that such interval may be longer than 2 months in some cases, and that fertility may actually be increased during the first 2-4 weeks post-treatment.

Topics: Animals; Contraceptive Agents, Male; Dogs; Drug Implants; Infertility, Male; Male; Semen; Semen Analysis; Sperm Count; Sperm Motility; Time Factors; Triptorelin Pamoate

The aim of this study was to evaluate the practical use of Deslorelin in a clinical setting to induce oestrus and ovulation and to assess pregnancy rates. Sixteen anoestrus bitches that were brought into the clinic were implanted subcutaneously in the ventral abdomen with Deslorelin. Implants were removed after ovulation was assumed to have occurred. All bitches came into oestrus and 13 ovulated. 11 of 16 bitches became pregnant (68.8%) and all continued to term. Average litter size was 7.6 puppies. On average, the implant was in place for 13.8 days.

Topics: Animals; Dogs; Estrus; Female; Ovulation; Pregnancy; Pregnancy, Animal; Triptorelin Pamoate

To detect differences in follicular fluid (FF) levels of amphiregulin (AR), depending on mode of triggering final oocyte maturation.. Prospective randomized trial.. Three IVF units.. Ninety-six patients undergoing IVF-intracytoplasmic sperm injection.. Ovulation triggered with either urinary hCG or GnRH agonist (GnRH-a).. 15 FF samples from small antral follicles (3-9 mm) and 12 FF samples from natural cycle.. Follicular fluid concentration of AR, P4, E2, vascular endothelial growth factor, and inhibin B.. Significantly lower levels of AR were found in FF from the GnRH-a group versus the hCG group, 51±3.5 versus 71±6.0 ng/mL. In FF from natural cycles, levels of AR were significantly higher than those of GnRH-a triggering but significantly lower than those of urinary hCG triggering. In small antral follicles only 5 out of 15 follicles contained measurable amounts of AR. When urinary hCG and GnRH-a triggering were compared, FF P4 was significantly higher after urinary hCG triggering, whereas no difference was seen regarding E2, vascular endothelial growth factor, and inhibin B. A total of 14% more metaphase II oocytes and 11% more transferable embryos were obtained after GnRH-a triggering.. This study suggests that oocyte competence is linked to granulosa cell AR secretion.

Topics: Adult; Amphiregulin; Chorionic Gonadotropin; EGF Family of Proteins; Epidermal Growth Factor; Female; Fertilization in Vitro; Follicular Fluid; Glycoproteins; Gonadotropin-Releasing Hormone; Humans; Intercellular Signaling Peptides and Proteins; Menotropins; Ovulation Induction; Peptides; Pregnancy; Pregnancy Rate; Triptorelin Pamoate

It remains unclear how GnRH agonist (GnRHa) triggering affects the luteal phase, so we investigated the luteal phase after GnRHa triggering, supported with conventional E(2)/P with or without low-dose hCG. E(2)/P support, compared with low-dose hCG, induced a shorter luteal phase (11.2 ± 1.1 vs. 15.0 ± 1.6 days) and fewer subjective complaints (0 vs. 42%), whereas hCG caused more free fluid accumulation and enlarged ovaries than E(2)/P alone. Steroids and low-dose hCG differentially affected corpus luteum function, ovarian size, free fluid accumulation, and patient comfort.

Topics: Adult; Chorionic Gonadotropin; Comprehension; Dose-Response Relationship, Drug; Drug Combinations; Estradiol; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Luteal Phase; Luteinizing Hormone; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Progesterone; Reproductive Techniques, Assisted; Triptorelin Pamoate

Holstein cows received, subcutaneously 1 (1DESL, n=15) or 2 (2DESL, n=12) degradable implant containing 2.1mg of the GnRH agonist Deslorelin or no implant (CON, n=18) within 1.5 days postpartum (dpp). Previous pregnant (PPH) and non-pregnant (PNPH) uterine horns were determined by palpation per rectum. Cows were examined by ultrasonography at 8dpp, 15dpp, 22dpp, 29dpp, and 36dpp (S.E.=1 day) to record ovarian structures, cervical diameter, uterine horns cross-section and lumen diameters, myometrial and endometrial widths. Uterine tone was recorded before ultrasonography. Vaginoscopy was conducted just after ultrasonography for cervical discharge score. At 44dpp cows were inserted with a CIDR followed 7 days later by its removal and injection of PGF(2alpha) 8h later, followed by the Ovsynch 10 days after for timed artificial insemination (TAI). Plasma was analyzed for PGFM daily from parturition to 14dpp and for P(4) trice weekly until 44dpp. Additionally, strategic blood samples were collected during the synchronization protocol to determine whether estrous cyclicity was occurring and ovulation status before and after TAI, respectively. Cows in 1DESL and 2DESL groups had more class 1 follicles (P<0.01), less class 2 (P<0.01) and class 3 follicles (P<0.01) compared with CON. First increase of P(4), indicative of ovulation, occurred in CON (55.5%) cows at 28dpp (S.E.=9 days) and in 1DESL (13.3%) treated cows at 43dpp (S.E.=3). Plasma concentrations of P(4) were suppressed completely in all 2DESL-treated cows before initiation of estrous synchronization. Diameters of PPH (P<0.01), PNPH (P<0.01), uterine horn lumens (P<0.01) were less in the 1DESL and 2DESL groups with greater uterine tone (P=0.07). Frequency distribution of cervical discharge categories did not differ among groups. Proportion of cows with estrous cycles and having ovulations was less (P<0.01) in DESL implant cows compared with CON that was to a greater (P<0.01) extent in the 2DESL. Treatment with Deslorelin during postpartum (1) suppressed follicular development, (2) enhanced physical involution of the uterus, (3) increased tone of the uterine wall, (4) delayed first ovulation and reduced responsiveness to a synchronization of ovulation protocol. Future research should focus in GnRH agonist delivery systems to restrict duration of treatment to optimize uterine involution and avoid a prolonged period of anovulation.

Topics: Absorbable Implants; Animals; Cattle; Dairying; Dose-Response Relationship, Drug; Drug Implants; Estrus Synchronization; Female; Lactation; Organ Size; Ovary; Postpartum Period; Triptorelin Pamoate; Ultrasonography; Uterine Contraction; Uterus

This study was conducted to evaluate clinical efficacy of deslorelin for inhibiting reproduction in the bitch. Ten adult healthy bitches or bitches with mammary neoplasia for which owners were requesting suppression of cyclicity without performing gonadectomy were administered a 4.7- or a 9.4-mg deslorelin implant subcutaneously. The first implant of deslorelin was administered in anoestrus (n = 5) or in dioestrus (n = 5). Treatment was repeated every 5 months for as long as necessary based on the clinical situation of the dog and owner's desires. Some of the bitches implanted in anoestrus came in heat within 4-15 days after treatment, while none of the bitches implanted in dioestrus showed heat during treatment. Suppression of reproductive cyclicity was successfully achieved in 6/10 bitches for 1-4 years. No behavioural and local/general side-effects were observed in any of the treated bitches. The 4.7-mg deslorelin implant may work well for suppression of cyclicity provided that it is administered in dioestrus and at intervals of 4.5 months. A 9.4-mg implant may be more suitable for this use although its efficacy may also be shorter than 12 months. Owner compliance is an important limiting factor.

Topics: Animals; Dogs; Dose-Response Relationship, Drug; Drug Implants; Enzyme Inhibitors; Estrous Cycle; Female; Triptorelin Pamoate

Investigations using sustained-release deslorelin implants at various insertion sites have shown that this method consistently induces oestrus in anoestus bitches. However, fertility comparisons between implant insertion sites have not been performed. Anestrous beagle bitches received one 2.1 mg deslorelin implant beneath the vestibular mucosa (VM group; n = 6) or in the subcutaneous tissue between the shoulder blades (SubQ group; n = 8). Vestibular implants were removed when serum progesterone concentrations first exceeded 1.5 ng/ml. Vaginal cytologies and blood samples were collected daily and bitches were inseminated during oestrus. Serum progesterone and deslorelin concentrations were measured and pregnancy status was determined using ultrasonography. There were no differences between groups in the intervals between implant administration and the onset of proestrus, the time of the luteinizing hormone surge and the onset of cytologic diestrus. There were also no differences in the number of corpora lutea or foetuses. However, conception rate was significantly lower in the SubQ group. The pregnancy rate did not differ significantly between the VM and SubQ groups [4 out of 6 (66.7%) and 3 out of 8 (37.5%), respectively]. One bitch (16.7%) in the VM group and three bitches (37.5%) in the SubQ group suffered distinct, premature declines in serum progesterone concentrations starting 1-4 weeks after cytologic diestrus. Serum progesterone concentrations did not recover (premature luteal failure), resulting in abortion. Bitches with premature luteal failure in the SubQ group still had serum deslorelin concentrations >100 pg/ml 20 days after implant insertion, suggesting a possible association between prolonged deslorelin release and luteal failure.

Topics: Animals; Dogs; Drug Implants; Estrous Cycle; Female; Luteinizing Hormone; Ovulation Induction; Pregnancy; Triptorelin Pamoate; Vulva

The present study is part of a programme of research designed to evaluate the efficacy of the GnRH superagonist,deslorelin (D-Trp6-Pro9-des-Gly10-LHRH ethylamide), as a contraceptive for male dogs. Adult dogs were assigned to a completely randomized design comprising six groups of four animals. Each dog in the control group received a blank implant (placebo) and each dog in the other five groups received a 6 mg deslorelin implant. One group of deslorelin treated dogs was sacrificed on each of days 16, 26, 41, 101 and 620, and testicular and prostate tissues were collected for study by light and electron microscopy. On days 16 and 26 after implantation, we observed partial disruption of the seminiferous tubules, with early spermatids shed into the lumen. On days 41 and 101 after implantation, 90–100% of the seminiferous tubules were atrophic and aspermatogenic.On day 101 after implantation, 99% of all sections showed atrophy of the epithelium and shrinkage of epithelial height in the ductus epididymides. On days 41 and 101 after implantation, prostate tissue showed complete atrophy of the glandular epithelium (100% of sections) and an apparent increase in the relative proportion of connective tissue. At the electron microscopic level, in dogs treated with deslorelin for 41 and 101 days, the Sertoli cells were smaller and their nucleoli appeared smaller than in the control dogs. The nucleoli of the Leydig cells were atrophied and prostate glandular epithelium showed reduced epithelial height, a trophy of the nucleolus and an absence of secretory granules.Tissues collected during the recovery phase revealed a complete recovery of spermatogenesis. In conclusion, slow release implants containing deslorelin induce a striking a trophy of the testes and prostate gland by 26 days after implantation, explaining the previously reported loss of ejaculate and arrest of sperm output. At histological level,the entire process appears to be completely reversible, in accordance with data on endocrine variables and semen production.

Topics: Animals; Atrophy; Contraceptive Agents, Male; Dogs; Gonadotropin-Releasing Hormone; Male; Prostate; Testis; Triptorelin Pamoate

Surgical castration in ferrets has been implicated as an etiological factor in the development of hyperadrenocorticism in this species due to a castration-related increase in plasma gonadotropins. In search for a suitable alternative, the effect of treatment with the depot GnRH-agonist implant, deslorelin, on plasma testosterone concentrations and concurrent testes size, spermatogenesis, and the typical musky odor of intact male ferrets was investigated. Twenty-one male ferrets, equally divided into three groups, were either surgically castrated, received a slow release deslorelin implant or received a placebo implant. Plasma FSH and testosterone concentrations, testis size and spermatogenesis were all suppressed after the use of the deslorelin implant. The musky odor in the ferrets which had received a deslorelin implant was less compared to the ferrets which were either surgically castrated or had received a placebo implant. These results indicate that the deslorelin implant effectively prevents reproduction and the musky odor of intact male ferrets and is therefore considered a suitable alternative for surgical castration in these animals.

Topics: Animals; Contraceptive Agents, Male; Ferrets; Follicle Stimulating Hormone; Male; Odorants; Orchiectomy; Prostheses and Implants; Testis; Testosterone; Time Factors; Triptorelin Pamoate

Superovulation could potentially increase embryo recovery for immediate transfer or cryopreservation. The objectives were to evaluate the effect of pretreatment with progesterone and estradiol (P+E) on follicular response to eFSH and compare doses of eFSH and ovulatory agents on follicular development and ovulation in mares. In Experiment 1, 40 mares were assigned to one of four treatment groups. Group 1 consisted of untreated controls. Group 2 mares were administered eFSH without pretreatment with P+E. Group 3 mares were administered P+E for 10 days starting in mid-diestrus followed by eFSH therapy. Group 4 mares were administered P+E for 10 days followed by eFSH therapy. All treated mares were administered 12.5mg eFSH twice daily and prostaglandins were given on the second day of eFSH therapy. Mares were bred with fresh semen the day of hCG administration and with cooled semen the following day. The numbers of preovulatory follicles and ovulations were lower for mares treated with P+E prior to eFSH treatment. Pretreatment with P+E in estrus also resulted in a lower embryo recovery rate per ovulation compared to the other two eFSH treatment groups. In Experiment 2, two doses of eFSH (12.5 and 6.25mg) and two ovulation-inducing agents (hCG and deslorelin) were evaluated. The number of preovulatory follicles was greater for mares given 12.5mg of eFSH compared to mares given 6.25mg. Number of ovulations was greatest for mares given 12.5mg of eFSH twice daily followed by administration of hCG. Embryo recovery per flush was similar among treatment groups, but the percent of embryos per ovulation was higher for mares given the low dose of eFSH. In summary, there was no advantage to giving P+E prior to eFSH treatment. In addition, even though the lower dose of eFSH resulted in fewer ovulations, embryo recovery per flush and embryo recovery per ovulation were similar or better for those given the lower dose of eFSH.

Topics: Animals; Chorionic Gonadotropin; Dose-Response Relationship, Drug; Estradiol; Female; Follicle Stimulating Hormone; Horses; Ovarian Follicle; Ovary; Progesterone; Superovulation; Triptorelin Pamoate

The objectives of this study were to confirm: (i) whether progestin treatment suppressed GnRH agonist-induced estrus in anestrous greyhound bitches; and (ii) the site of progestin action (i.e. pituitary, ovary). All bitches received a deslorelin implant on Day 0 and blood samples were taken from -1 h to +6 h. Five bitches were treated with megestrol acetate (2 mg/kg orally once daily) from -7 d to +6 d (Group 1) and 10 bitches were untreated controls (Group 2). Proestrous or estrous signs were observed in 4 of 5 bitches in Group 1, and 4 of 10 bitches in Group 2 (P = 0.28). The plasma LH responses (area under the curve from 0 to 6h after implantation) were higher (P = 0.008) in Group 2 than in Group 1. Plasma LH responses were similar (P = 0.59) in bitches showing signs of proestrus or estrus (responders) and in non-responders. The plasma estradiol responses (calculated as for LH response) were greater in Group 1 than in Group 2 (P = 0.048), and in responders than in non-responders (P = 0.02).. (i) progestin treatment (a) did not suppress the incidence of bitches showing deslorelin-induced proestrus or estrus, and (b) was associated with a reduced pituitary responsiveness and an increased ovarian responsiveness to deslorelin treatment; (ii) the occurrence of proestrous or estrous signs reflected increased ovarian responsiveness to induced gonadotrophin secretion and not increased pituitary responsiveness to deslorelin.

Topics: Anestrus; Animals; Dogs; Drug Implants; Estradiol; Estrus; Female; Luteinizing Hormone; Megestrol Acetate; Progesterone; Progestins; Triptorelin Pamoate

Non-lactating OVX Holstein cows (N = 34) were used to investigate the effect of s.c. placement of an absorbable GnRH agonist implant (Ovuplant; deslorelin 2.1mg, Peptech Animal Health, Australia) on the relationship of plasma LH, oestradiol responsiveness and pituitary LH content. On the day of implant insertion (Day 0), one group (OVU-48h; N = 5) received Ovuplant and had blood samples collected at hourly intervals to characterize the LH response, while a second group (CON-48 h; N = 5) remained untreated and acted as controls. Blood samples were collected every 10 min over 6 h from CON-48 h and OVU-48 h, at 24 h post-implant insertion. These cows were then slaughtered at 48 h post-implant insertion and their pituitaries recovered. Another group received Ovuplant (OVU-21d+E2; N = 10) or were left untreated (CON-21d+E2) and 21 days later were injected i.m. with 0.5 mg 17beta-E2. Blood samples were collected every 10 min for 4 h on the day before E2 injection to characterize LH pulse frequency and amplitude. Beginning 14 h later, blood samples were collected hourly for 12 h to characterize the expected LH surge. These cows were slaughtered and their pituitary glands recovered and assayed for LH and FSH content. Peak plasma LH concentrations (59 +/- 19 ng/ml) were measured after 30 min of Ovuplant insertion. They had returned to pre-treatment levels by 7 h. By 24 h post-implant insertion, OVU-48 h plasma LH profiles were characterized by reduced LH pulse frequency (0.23 +/- 0.09 pulses/h versus 0.75 +/- 0.26 pulses/h; OVU-48 h versus CON-48 h; P < 0.05). The cows that received Ovuplant had lower LH pulse amplitude, LH pulse frequency and mean LH concentrations after 20 days. Injection of 0.5 mg 17beta-E2 induced an LH surge in every one of the control cows with their peak concentrations measured 18 h post injection. No increase in LH was detected in any Ovuplant treated cows. Pituitary FSH content was reduced in Ovuplant treated cows after 48 h, but not that of LH. In conclusion, absorbable deslorelin implants induced a substantial but temporary release of LH, but even 21 days later their LH profiles were characterized by marked suppression of pulsatile LH and an absence of response to E2. These results suggest the implant has prolonged biological activity.

Topics: Absorption; Animals; Cattle; Drug Implants; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Kinetics; Luteinizing Hormone; Organ Size; Ovariectomy; Pituitary Gland; Triptorelin Pamoate

This study investigated the reproductive effects in Holstein-Friesian cows of once or twice weekly intramuscular injection for 6 weeks of 100 microg of the GnRH agonist deslorelin at intervals. Oestrus was synchronized in non-lactating Holstein-Friesian cows before they were allocated randomly to receive either 100 microg deslorelin once weekly (D1; N=10) or twice weekly (D2; N=8) or acted as untreated controls (CON; N=8). The first injection was given on day 6 post-oestrus and the last injection on day 48 post-oestrus. Blood samples were collected twice weekly from each cow until day 76 after the synchronized oestrus to profile plasma P4. A single injection of prostaglandin was administered to all cows on day 20 post-oestrus to ensure luteolysis occurred. Ovaries were examined twice weekly by transrectal ultrasonography and then subsequently at weekly intervals to monitor ovarian structures. Progesterone profiles observed over two complete cycles for CON cows were typical of those expected for cows displaying regular oestrous cycles. Injection of deslorelin on day 6 post-oestrus induced ovulation in 100% (18/18; D1 and D2) of deslorelin-treated cows. Three categories of responses based on plasma P4 profiles were defined amongst the deslorelin-treated cows. Complete anoestrus was observed in 20% (2/10) of D1 and 63% (5/8) of D2 cows. A partial response characterised by intermittently low concentrations of P4 was observed in 50% (5/10) of D1 and 25% (2/8) of D2. A complete lack of response to deslorelin, with P4 profiles indistinguishable from CON cows, was seen in 30% (3/10) of D1 and 13% (1/8) of D2 cows. When results from D1 and D2 were pooled, a greater proportion of deslorelin-treated cows had abnormal ovarian cycles during the treatment period (56% versus 0%; D1 and D2 versus CON, P <0.001). In conclusion, the repeated injection of deslorelin either once or twice weekly for 6 weeks significantly altered the ovarian cycles of some cows; individual cow responses observed varied widely and ranged from complete anoestrus to a cycle indistinguishable from normal.

Topics: Animals; Cattle; Cloprostenol; Estrous Cycle; Estrus; Estrus Synchronization; Female; Injections, Intramuscular; Ovulation Induction; Progesterone; Reproduction; Time Factors; Triptorelin Pamoate

To evaluate the clinical and endocrine responses of ferrets with adrenocortical disease (ACD) to treatment with a slow-release implant of deslorelin acetate.. 15 ferrets with ACD.. Ferrets were treated SC with a single slow-release, 3-mg implant of deslorelin acetate. Plasma estradiol, androstenedione, and 17-hydroxyprogesterone concentrations were measured before and after treatment and at relapse of clinical signs; at that time, the adrenal glands were grossly or ultrasonographically measured and affected glands that were surgically removed were examined histologically.. Compared with findings before deslorelin treatment, vulvar swelling, pruritus, sexual behaviors, and aggression were significantly decreased or eliminated within 14 days of implantation; hair regrowth was evident 4 to 6 weeks after treatment. Within 1 month of treatment, plasma hormone concentrations significantly decreased and remained decreased until clinical relapse. Mean time to recurrence of clinical signs was 13.7 +/- 3.5 months (range, 8.5 to 20.5 months). In 5 ferrets, large palpable tumors developed within 2 months of clinical relapse; 3 of these ferrets were euthanatized because of adrenal gland tumor metastasis to the liver or tumor necrosis.. In ferrets with ACD, a slow-release deslorelin implant appears promising as a treatment to temporarily eliminate clinical signs and decrease plasma steroid hormone concentrations. Deslorelin may not decrease adrenal tumor growth in some treated ferrets. Deslorelin implants may be useful in the long-term management of hormone-induced sequelae in ferrets with ACD and in treatment of animals that are considered at surgical or anesthetic risk.

Topics: Adrenal Cortex Diseases; Aging; Animals; Drug Implants; Female; Ferrets; Gonadal Steroid Hormones; Male; Recurrence; Triptorelin Pamoate

Treatment with a luteinizing hormone-releasing hormone (LHRH) agonist increases adult height in children with LHRH-dependent precocious puberty and is prescribed by some practitioners to augment height in short adolescents. We performed a randomized clinical trial to determine whether treatment with an LHRH agonist increases adult height in short adolescents with normally timed puberty.. Fifty short adolescents (18 boys and 32 girls) with low predicted adult height (mean [+/-SD], 3.3+/-1.2 SD below the population mean) received either placebo (24 subjects) or an LHRH agonist (26 subjects). The mean (+/-SD) duration of treatment was 3.5+/-0.9 years in the LHRH-agonist group and 2.1+/-1.2 years in the placebo group (P<0.001). Adult height was measured when bone age exceeded 16 years in girls and 17 years in boys and when the rate of growth was less than 1.5 cm per year.. Forty-seven adolescents (94 percent) were followed until they attained adult height. At the time adult height was achieved, the subjects who had been treated with an LHRH agonist were older than those who had received placebo (20.5+/-2.1 years vs. 18.0+/-2.5 years, P=0.01) and were taller (standard-deviation score, -2.2+/-1.1 vs. -3.0+/-1.2; P=0.01). Analysis of covariance showed that LHRH-agonist treatment resulted in an increase of 0.6 (95 percent confidence interval, 0.2 to 0.9) in the standard-deviation score for height, or an increase of 4.2 cm (95 percent confidence interval, 1.7 to 6.7), over the initially predicted adult height (P=0.01). Treatment with an LHRH agonist resulted in significantly greater adult height than did placebo in boys and girls, in adolescents with idiopathic short stature, and in those who had a growth-limiting syndrome. The principal adverse event in the LHRH-agonist group was decreased accretion of bone mineral density (mean lumbar vertebral bone mineral density at the time adult height was achieved, 1.6+/-1.2 SD below the population mean, vs. 0.3+/-1.2 SD below the population mean in the placebo group; P<0.001).. Treatment with an LHRH agonist for 3.5 years increases adult height by 0.6 SD in adolescents with very short stature but substantially decreases bone mineral density. Such treatment cannot be routinely recommended to augment height in adolescents with normally timed puberty.

Topics: Adolescent; Body Height; Bone Density; Child; Double-Blind Method; Enzyme Inhibitors; Female; Follicle Stimulating Hormone; Growth; Growth Disorders; Humans; Luteinizing Hormone; Male; Puberty; Triptorelin Pamoate

Two experiments were conducted to investigate the use of a bioabsorbable implant of the GnRH agonist deslorelin to temporarily delay the resumption of postpartum ovulatory cycles in Holstein cows. In Experiment 1, recently calved cows were paired and received either a single implant (Ovuplant); Peptech Animal Health, Sydney, NSW, Australia) within 48 h of parturition (OVP; n=17), or remained as untreated controls (CON; n=17). Blood samples were collected for plasma progesterone assay three times weekly for 6 weeks to profile the pattern of resumption of ovulatory cycles. In Experiment 2, there were 15 CON and 15 OVP cows initially treated as for Experiment 1 as well as 15 OVP+SYNCH cows. Each cow in the CON and OVP+SYNCH groups received a progesterone vaginal insert (CIDR); Genetics Australia, Bacchus Marsh, Vic., Australia) for 7 days at 23 days postpartum (23 dpp) to synchronise estrus in cycling animals or to induce an ovulation with estrus in anestrus animals. Blood samples were collected weekly until removal of the CIDR insert, and then twice weekly until 56 dpp to monitor plasma P4 for retrospective determination of ovulation. Milk yield was monitored by twice daily electronic volume measurements and milk composition with once weekly milk composition analysis. In Experiment 1, CON cows began ovulating from 9 dpp; 15 of 17 had ovulated by the end of blood sampling at 42 dpp. None of the OVP cows ovulated until at least 24 dpp, and only 6 of 17 had ovulated by 42 dpp. The average day of first ovulation was extended from 22.4+/-2.7 dpp to 39.3+/-2.7 dpp (P<0.05). In Experiment 2, ovulation had occurred in 8 of 15 CON cows at the time of CIDR insertion (23 dpp), 0 of 15 OVP cows and 1 of 15 OVP+SYNCH cows. By 40 dpp (or 10 days following removal of the CIDR insert) every CON cow (15/15) had ovulated, but only 2 of 15 OVP+SYNCH cows and 1 of 15 OVP cows. None of these effects of treatment was associated with any changes in milk yield or composition in either experiment. In conclusion, inserting a bioabsorbable implant of deslorelin within 48 postpartum extended the interval to first ovulation to at least 24 dpp in 46 of 47 cows. Recovery periods were highly variable. This variability was not reduced by using a form of intravaginal progesterone supplementation that did produce a synchronised estrus with ovulation in anestrus animals that had not been treated with deslorelin.

Topics: Absorption; Administration, Intravaginal; Anestrus; Animals; Cattle; Drug Implants; Estrus Synchronization; Female; Lactation; Ovulation; Postpartum Period; Progesterone; Time Factors; Triptorelin Pamoate

To investigate the possibility that more complete blockade of androgens or combined androgen blockade (CAB) could lead to even longer term control of localized prostate cancer. A series of recent studies have shown important benefits on survival using medical or surgical castration in localized or locally advanced prostate cancer.. The effect of CAB on long-term control or possible cure of prostate cancer was evaluated by the absence of biochemical failure or prostate-specific antigen (PSA) rise for at least 5 years after cessation of continuous treatment. A total of 57 patients with localized or locally advanced disease received CAB for periods ranging from 1 to 11 years. Twenty patients with Stage B2/T2 prostate cancer who were treated for a median duration of 7.2 years (range 2.8 to 11.7) with CAB stopped treatment and were followed up for a median of 4.9 years. Eleven patients with Stage B2/T2 also received CAB but for only 1 year. Twenty-six patients with Stage C/T3 treated with continuous CAB for a median of 9.9 years (range 3.8 to 11.3) with undetectable PSA levels stopped treatment and were followed up for a median of 5.6 years. The median follow-up since diagnosis was 14.6 years for patients with Stage B2/T2 and 16.4 years for patients with Stage C/T3 disease.. With a minimum of 5 years of follow-up after cessation of long-term CAB, two PSA rises occurred among 20 patients with Stage T2-T3 cancer who stopped treatment after continuous CAB for more than 6.5 years, for a nonfailure rate of 90%. For the 11 patients who had received CAB for 3.5 to 6.5 years, the nonfailure rate was only 36%. The serum PSA increased within 1 year in all 11 patients with Stage B2/T2 treated with CAB for only 1 year, thus indicating that active cancer remained present after short-term androgen blockade despite undetectable PSA levels. In all patients who had biochemical failure after stopping CAB, the serum PSA level rapidly decreased again to undetectable levels when CAB was restarted and remained at such low levels afterward. Of these patients, only 1 patient had died of prostate cancer at last follow-up.. The present data suggest that long-term and continuous CAB offers the possibility of long-term control or possible cure of localized prostate cancer.

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Therapy, Combination; Flutamide; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Longitudinal Studies; Male; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Treatment Outcome; Triptorelin Pamoate

To evaluate gonadotropin secretion and ovarian function after administration of deslorelin acetate to induce ovulation in mares.. Randomized controlled trial.. 16 healthy mares with normal estrous cycles.. 8 control mares were allowed to ovulate spontaneously, whereas 8 study mares received deslorelin to induce ovulation when an ovarian follicle > 35 mm in diameter was detected. Follicle development and serum concentrations of gonadotropins were monitored daily during 1 estrous cycle. Pituitary responsiveness to administration of gonadotropin-releasing hormone (GnRH) was evaluated 10 days after initial ovulation.. Interovulatory intervals of mares treated with deslorelin (mean +/- SD, 25.6 +/- 2.6 days) were longer than those of control mares (22.9 +/- 1.8 days). Diameter of the largest follicle was significantly smaller during 2 days of the diestrous period after ovulation in deslorelin-treated mares than in control mares. Concentrations of follicle-stimulating hormone (FSH) were lower in deslorelin-treated mares on days 5 through 14 than in control mares. Concentrations of luteinizing hormone were not different between groups during most of the cycle. Gonadotropin release in response to administration of GnRH was lower in mares treated with deslorelin acetate than in control mares.. Administration of deslorelin was associated with reduction in circulating concentrations of FSH and gonadotropin response to administration of GnRH during the estrous cycle. Low concentration of FSH in treated mares may lead to delayed follicular development and an increased interovulatory interval.

Topics: Animals; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Gonadotropins; Horses; Ovarian Follicle; Ovulation Induction; Time Factors; Triptorelin Pamoate

The objective of the present study was to determine the effect of level of feed intake of pasture on P4 clearance rates in dairy cows. Twelve non-lactating Holstein-Friesian cows aged 4-9 years were randomly allocated to a restricted or ad libitum group. The ad libitum group had unrestricted access to irrigated pasture, whereas the restricted group had access for only 2h per day. Each animal was drenched orally twice daily with a chromic oxide capsule to allow daily feed intake to be estimated from faecal output (FO). Endogenous progesterone (P4) production was eliminated by subcutanously implanting a capsule containing 6 mg of a potent GnRH-agonist (deslorelin) into the ear of each animal 3 weeks before inserting a CIDR device containing 1.9 g P4 into the vagina. Two luteolytic PGF2alpha were given 10 days later. Each device was removed after 11 days and residual P4 measured. Daily plasma samples were assayed for P4. Faecal samples were also taken daily and assayed for pregnanes (FP4M) containing a 20-oxo-, a 20alpha- or a 20beta-OH group with EIAs. The average daily dry matter (DM) intake of pasture was higher for cows in the ad libitum group (15.9 versus 6.3 kg DM, P=0.001). Their plasma P4 concentrations were lower (1.08 versus 1.71 ng/ml, P=0.05), even though the average residual P4 content of the used CIDR devices was not affected by feed intake (1.20 versus 1.25 g, P>0.05). The concentrations of FP4M were not affected by level of feed intake (20-oxo-: 3.3 versus 1.7, 20alpha-: 3.5 versus 3.7, 20beta-: 2.1 versus 3.2 microg/g DM). Daily excretion rates of 20-oxo- and 20alpha- were higher in ad libitum cows (20-oxo-: 17.8 versus 4.3mg per day, P=0.05; 20alpha-: 18.2 versus 8.9 mg per day, P=0.001), but daily yield of faecal 20beta- was not affected by feed intake (11.9 versus 8.6 mg per day, P=0.5). These results show that there was a negative relationship between feed intake and plasma P4 concentrations in these CIDR-treated GnRH-downregulated Holstein cows. Concentrations of FP4M were not affected by level of feed intake or FO, but daily excretion rate of FP4M was associated with the volume of faeces.

Topics: Animals; Body Weight; Cattle; Diet; Dinoprost; Eating; Feces; Female; Food Deprivation; Gonadotropin-Releasing Hormone; Metabolic Clearance Rate; Pregnanes; Progesterone; Triptorelin Pamoate

Concern has been raised that children with central precocious puberty (CPP) are prone to the development of obesity. Here we report longitudinal height, weight, and body mass index (BMI) data from 96 girls and 14 boys with CPP before, during, and after GnRH agonist (GnRHa) administration. Skinfold thickness (n = 46) and percent body fat by dual energy x-ray absorptiometry (n = 21) were determined in subsets for more accurate assessment of body composition and to validate the use of the BMI SD score as an index of body fatness in our subjects. Before the initiation of therapy (PRE), the girls with CPP had a mean BMI SD score for chronological age (CA) of 1.1+/-0.1 and for bone age (BA) of 0.1+/-0.1. By the end of the study, 12-24 months after the discontinuation of GnRHa, the mean BMI SD score was 0.9+/-0.1 for CA and 0.6+/-0.1 for BA. At the visit when GnRHa was discontinued, 41% and 22% of the girls had a BMI SD score for CA more than the 85th and 95th percentiles, respectively, indicating that obesity was present at a high rate among our subjects; the BMI SD score for CA at the PRE visit was its strongest predictor. Indeed, 86% of the girls with BMI SD score for CA above the 85th percentile when GnRHa was discontinued also had BMI SD score for CA above the 85th percentile at the PRE visit. The proportion of boys with elevated BMI SD score for CA was also high. Fifty-four percent and 31% of the SD scores were greater than the 85th and 95th percentiles after 36 months of GnRHa therapy; the BMI SD score for CA PRE had been above the 85th percentile in 71% of these overweight subjects. Obesity occurs at a high rate among children with CPP, but does not appear to be related to long term pituitary-gonadal suppression induced by GnRHa administration. Children with CPP should have a baseline BMI SD score calculated, and those at risk for obesity should be counseled appropriately.

Topics: Adolescent; Body Composition; Body Height; Body Mass Index; Child; Child, Preschool; Female; Gonadotropin-Releasing Hormone; Humans; Male; Obesity; Puberty, Precocious; Skinfold Thickness; Triptorelin Pamoate; Weight Gain

Although treatment of girls with precocious puberty should ideally restore estradiol levels to the normal prepubertal range, treatment effectiveness has usually been monitored by gonadotropin levels because estradiol RIAs have lacked sufficient sensitivity to monitor treatment effectiveness. We hypothesized that a recently developed ultrasensitive recombinant cell bioassay for estradiol would have sufficient sensitivity to demonstrate a dose-dependent suppression of estradiol during LH-releasing hormone agonist treatment and to determine whether currently used doses are able to suppress estradiol levels to the normal prepubertal range. Twenty girls with central precocious puberty were assigned randomly to receive deslorelin for 9 months at a dose of 1, 2, or 4 micrograms/ kg.day. A significant dose-response relationship was observed, with mean +/- SD estradiol levels of 16.7 +/- 6.1, 7.9 +/- 1.6, and 6.5 +/- 0.7 pmol/L at the doses of 1, 2, and 4 micrograms/kg.day, respectively (P < 0.01). The highest dose suppressed estradiol levels to just above the 95% confidence limits for normal prepubertal girls (< 0.07-6.3 pmol/L). We conclude that the ultrasensitive bioassay for estradiol has sufficient sensitivity for monitoring the response to LH-releasing hormone agonist treatment of central precocious puberty. Additionally, the observation that the deslorelin dose of 4 micrograms/kg.day did not fully restore estradiol levels to the normal prepubertal range suggests that some girls with precocious puberty may require higher doses to receive the maximal benefit of treatment. We suggest that restoration of estradiol levels to the normal prepubertal range should be the ultimate biochemical measure of efficacy, as estradiol is the key hormone that accelerates growth rate, bone maturation rate, and breast development in girls with precocious puberty.

Topics: Biological Assay; Child; Dose-Response Relationship, Drug; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Puberty, Precocious; Receptors, LHRH; Sensitivity and Specificity; Triptorelin Pamoate

The influence of Buserelin injection and Deslorelin (a GnRH analogue) implants administered on Day 5 of the estrous cycle on plasma concentrations of LH and progesterone (P4), accessory CL formation, and follicle and CL dynamics was examined in nonlactating Holstein cows. On Day 5 (Day 1 = ovulation) following a synchronized estrus, 24 cows were assigned randomly (n = 4 per group) to receive 2 mL saline, i.m. (control), 8 micrograms, i.m. Buserelin or a subcutaneous Deslorelin (DES) implant in concentrations of 75 micrograms, 150 micrograms, 700 micrograms or 2100 micrograms. Blood samples were collected (for LH assay) at 30-min intervals for 2 h before and 12 h after GnRH-treatment from cows assigned to Buserelin, DES-700 micrograms and DES-2100 micrograms treatments and thereafter at 4-h intervals for 48 h. Beginning 24 h after treatment, ovaries were examined by ultrasound at 2-h intervals until ovulation was confirmed. Thereafter, ultrasonography and blood sampling (for P4 assay) was performed daily until a spontaneous ovulation before Day 45. A greater release of LH occurred in response to Deslorelin implants than to Buserelin injection (P < 0.01). Basal levels of LH between 12 and 48 h were higher in DES-700 micrograms group than in DES-2100 micrograms and Buserelin (P < 0.05). The first wave dominant follicle ovulated in all cows following GnRH treatment. Days to CL regression did not differ between treatments, but return to estrus was delayed (44.2 vs 27.2 d; P < 0.01) in cows of DES-2100 micrograms group. All GnRH treatments elevated plasma P4 concentrations, and the highest P4 responses were observed in the DES-700 micrograms and DES-2100 micrograms groups. The second follicular wave emerged earlier in GnRH-treated than in control cows (9.9 vs 12.8 d; P < 0.01). However, emergence of the third dominant follicle was delayed in cows of DES-2100 micrograms treatment (37.0 d) compared with DES-700 micrograms (22.2 d), Buserelin (17.8 d) or control (19.0 d). In conclusion, Deslorelin implants of 700 micrograms increased plasma P4 and LH concentrations and slightly delayed the emergence of the third dominant follicle. On the contrary, Deslorelin implants of 2100 micrograms drastically altered the P4 profiles and follicle dynamics.

Topics: Animals; Buserelin; Cattle; Corpus Luteum; Drug Implants; Estrus; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Humans; Infant; Kinetics; Luteinizing Hormone; Ovarian Follicle; Ovulation Induction; Progesterone; Triptorelin Pamoate

In two separate controlled clinical trials, the efficacy and safety of 2.2 mg of the GnRH analogue deslorelin, administered subcutaneously as a short-term implant to normally cycling mares in oestrus with a dominant ovarian follicle more than 30 mm in diameter, were evaluated, using a placebo as a negative control. The oestrous cycle of each mare was followed by teasing, palpation per rectum and transrectal ultrasonography. Follicles were monitored every 24 hours by ultrasonography until ovulation occurred. The mares were either mated naturally or inseminated artificially. In trial 1, 174 mares were treated at six locations in Canada, and in trial 2, 98 mares were treated at three locations in the USA. In trial 1, the treatment with deslorelin reduced the mean (sd) time to ovulation from 84.2 (48.4) hours to 50.2 (19.6) hours (P < 0.001) and in trial 2 it reduced it from 88.8 (40.3) hours to 54.1 (26.5) hours (P < 0.001). In trial 1, the percentage of mares ovulating within 48 hours increased from 37.7 per cent in control mares to 86.1 per cent in treated mares (P < 0.001) and in trial 2 the percentage increased from 26.5 to 80.9 per cent (P < 0.001). In trial 2, the duration of oestrus in the deslorelin-treated mares was reduced from 6.1 days to 4.3 days and the number of matings or artificial inseminations was reduced from 2.5 to 1.7 (P < 0.001). In trial 1, days 12 to 20 pregnancy rates for matings at the treatment oestrus were not different for deslorelin-treated (75.6 per cent) and placebo-treated (66.1 per cent) mares. In trial 2, days 12 to 20 pregnancy rates from matings at the treatment oestrus were lower for deslorelin-treated (58.7 per cent) than for placebo-treated (83.3 per cent) mares (P < 0.05), although pregnancy rates were similar for deslorelin-treated (97.1 per cent) and placebo-treated (95.0 per cent) mares after mating at the second oestrus. In both trials, pregnancy losses due to early or late abortions were within the normally expected range and similar for deslorelin-treated (3.6 and 3.7 per cent, respectively) and placebo-treated (13.4 and 7.5 per cent) mares. The treatments did not cause systemic side effects and local reactions at the implantation sites were slight and of short duration.

Topics: Animals; Drug Implants; Enzyme Inhibitors; Estrus; Female; Gonadotropin-Releasing Hormone; Horses; Humans; Infant, Newborn; Ovulation; Pregnancy; Triptorelin Pamoate

Agonists of GnRH were examined for their potential to achieve controlled, reversible suppression of estrous cycles in beef cattle. In Exp. 1, cyclic heifers received two (Group B2) or four (Group B4) buserelin (D-Ser[Bu(t)]6-Pro9-LHRH[1-9] nonapeptide ethylamide) implants and degree of cessation of estrous cycles was monitored. Treatment with buserelin caused estrous cycles to cease, as indicated by basal (.2 ng/mL) concentrations of progesterone, for 48.4 +/- 3.8 d (mean +/- SEM) in Group B2, which was less (P = .6) than the 87.4 +/- 17.4 d in Group B4. In Exp. 2, heifers treated with one (Group D1) or two (Group D2) implants of deslorelin (D-Trp6-Pro9-des-Gly10-LHRH ethylamide) had basal progesterone concentrations for 203 +/- 26 d (Group D1) and 170 +/- 28 d (Group D2; P > .05). In Exp. 3, stage of the estrous cycle was synchronized in cows, and, on d 7 of the ensuing cycle, cows received four deslorelin implants for 28 (Group D28) or 56 d (Group D56). Treatment with deslorelin induced an acute increase in plasma concentrations of immunoactive and bioactive LH, which remained increased over 7 d of observation. Based on profiles of progesterone, cows did not develop a functional corpus luteum during deslorelin treatment. Days to first and second estrus after implant removal were similar for cows in Group D28 (23.6 +/- 2.1 and 40.2 +/- 4.2 d, respectively) and Group D56 (21.5 +/- 3.3 and 44.3 +/- 2.9 d). The findings indicated that GnRH agonists block estrous cycles in cattle. Also, estrous cycles returned after discontinuation of treatment. Furthermore, the consistent and predictable responses detected in cows after implant removal indicated that agonists should be suitable for achieving a controlled, reversible suppression of estrous cycles in cattle.

Topics: Animals; Buserelin; Cattle; Dose-Response Relationship, Drug; Drug Implants; Estrus; Female; Gonadotropin-Releasing Hormone; Progesterone; Triptorelin Pamoate

In a blinded trial, the effectiveness and safety of 2.2 mg of the GnRH analog deslorelin acetate, administered in a short-term implant (STI) to normally cycling mares in estrus with a dominant ovarian follicle of 30 mm in diameter or larger, were evaluated, using a placebo implant as a negative control. A total of 39 mares received treatments at admittance with pre-randomized implants containing either 2.2 mg or 0 mg deslorelin. Mares were teased daily and examined rectally with ultrasound at 24 h intervals to determine time to ovulation and duration of estrus. The number of breedings and the pregnancy rate at 18 (+/- 3) and 38 (+/- 3) days were recorded, as were systemic side effects and local reactions at the implantation sites. Pregnancies resulting from breedings during the treatment estrus and/or from breedings during the next estrus were followed and the early and late pregnancy loss rate, the number of pregnancies going to term and of live-born foals was recorded. Mean follicle diameter at treatment was not significantly different between the deslorelin and placebo treatment group with 41.6 mm and 40.8 mm, respectively. Treatment with deslorelin STI reduced the time interval to ovulation significantly from 69.5 +/- 25.48 h to 42.7 +/- 12.35 h (p < 0.001). The percentage of mares having ovulated within 48 h rose from 26.3% to 95.0%, respectively, for placebo and deslorelin STI (p < 0.001). As a consequence, the duration of estrus in days and the percent of animals requiring more than 1 breeding were significantly reduced in deslorelin treated animals from 5.4 days to 4.6 days, and from 55.6% to 5.0%, respectively (p = 0.009 and = 0.001). The percent of mares pregnant from breedings at the treatment estrus (65.0% versus 44.4%) or the next estrus (83.3% versus 92.3%) was satisfactory and similar for deslorelin and placebo treated mares (p > 0.005), and in 70.0% and 66.7% of these once or twice bred mares did pregnancies go to term and live foals were born.

Topics: Animals; Double-Blind Method; Drug Implants; Enzyme Inhibitors; Estrus; Estrus Detection; Female; Gonadotropin-Releasing Hormone; Horses; Ovulation; Pregnancy; Time Factors; Triptorelin Pamoate

LH-releasing hormone agonist (LHRHa) treatment slows bone maturation and improves adult height in children with LHRH-dependent precocious puberty. To determine whether pubertal delay induced by LHRHa can enhance final height in patients with short stature and a normally timed puberty, we enrolled 43 short children (28 girls and 15 boys) in a double blind, placebo-controlled trial. Patients were assigned randomly to receive either placebo or LHRHa (deslorelin), administered sc at a dose of 4 micrograms/kg.day for a period of 4 yr. This report describes the preliminary results in 16 children who have completed 4 yr of treatment (9 patients in the deslorelin group and 7 patients in the placebo group). Predicted adult height increased significantly in the deslorelin-treated patients, by 7.6 cm compared to the pretreatment baseline and by 10.3 cm compared to that in the placebo-treated patients (P < 0.005). Four of the 16 patients received concurrent GH treatment (3 among the deslorelin-treated patients and 1 among the placebo-treated patients). Omitting these patients from the analysis did not materially affect the results: predicted adult height in the deslorelin-treated patients increased by 7.2 cm compared to the pretreatment baseline and by 10.9 cm compared to that in the placebo-treated patients (P < 0.005). We conclude that pubertal delay induced by deslorelin significantly increases predicted adult height in adolescents with short stature and a normally timed puberty. Whether deslorelin treatment will increase the final height of these patients cannot be determined until they have stopped growing.

Topics: Adolescent; Body Height; Bone Development; Double-Blind Method; Female; Forecasting; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Male; Puberty; Triptorelin Pamoate

Combined antiandrogen (spironolactone) and aromatase inhibitor (testolactone) are effective for the short term treatment of familial male precocious puberty. During this therapy, plasma testosterone levels remain in the adult range, since spironolactone blocks the testosterone receptor without significantly affecting plasma testosterone levels. After our initial 18-month pilot study, we continued to treat eight boys with the combined therapy for 2.0-4.2 yr. During this time all boys exhibited a pubertal rise in gonadotropin secretion and a diminishing response to treatment, which was manifested by the recurrence of clinical features of puberty and an increase in the bone maturation rate (P < 0.05). Addition of the LHRH agonist deslorelin (4 micrograms/kg.day, sc) to the combined therapy decreased peak LH, plasma testosterone, bone maturation rate, and growth velocity (P < 0.05) over the next year. We conclude that the rise in gonadotropin levels during central activation of hypothalamic LHRH secretion in boys with familial male precocious puberty causes a partial escape from the combined effect of spironolactone and testolactone. The addition of deslorelin to the combined therapy appears to restore the control of puberty in this setting.

Topics: Age Determination by Skeleton; Body Height; Bone Development; Child; Child, Preschool; Drug Therapy, Combination; Follicle Stimulating Hormone; Follow-Up Studies; Gonadotropin-Releasing Hormone; Growth; Humans; Luteinizing Hormone; Male; Pilot Projects; Puberty, Precocious; Spironolactone; Testolactone; Testosterone; Triptorelin Pamoate

To determine if gonadotropin suppression improves ovarian follicle function or ovulation rates in patients with karyotypically normal spontaneous premature ovarian failure.. Prospective, double-blind, placebo-controlled, crossover trial.. Tertiary care research institution.. Two intervention phases lasting 4 months each: one placebo phase, and one treatment phase during which each patient received daily subcutaneous injections of 300 micrograms of the gonadotropin-releasing hormone agonist (GnRH-a) deslorelin. During both phases, patients took a standardized estrogen (E) replacement regimen.. Twenty-six patients with karyotypically normal spontaneous premature ovarian failure ranging in age from 18 to 39 years.. We measured serum estradiol (E2) and progesterone (P) levels weekly during the 2 months after each intervention. We defined a serum E2 greater than 50 pg/mL (184 pmol/L) as evidence for ovarian follicle function and a serum P greater than 3.0 ng/mL (9.5 nmol/L) as evidence for ovulation.. The GnRH-a therapy did not significantly enhance recovery of ovarian follicle function or the chance of ovulation. The power to detect a 40% and a 33% ovulation success rate with therapy was 0.95 and 0.83, respectively. We found evidence for ovarian follicle function in 11 of 23 women (48%), and 4 women (17%) ovulated.. Patients with karyotypically normal spontaneous premature ovarian failure treated with E replacement did not benefit from the additional gonadotropin suppression achieved with GnRH-a. Because these patients have a significant possibility of spontaneous remission, attempts to induce ovulation should be limited to controlled trials designed to determine safety and effectiveness.

Topics: Adult; Double-Blind Method; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Injections, Subcutaneous; Karyotyping; Primary Ovarian Insufficiency; Progesterone; Prospective Studies; Triptorelin Pamoate

Central precocious puberty is effectively treated with long-acting LHRH analogs (LHRHas). Although at least six LHRHas have now been used in children, there have been no studies to determine the least effective dose of any of these analogs. We sought to determine the effect of decreasing an efficacious dose of deslorelin (D-Trp6-Pro9-NEt-LHRH) on basal and LHRH-stimulated gonadotropins, estradiol levels, and the rates of linear growth and skeletal maturation in subjects with central precocious puberty. Twenty-nine children with central precocious puberty were enrolled in a double blinded study. All subjects were treated for the initial 3 months with deslorelin at a dose (4 micrograms/kg.day, sc) known to suppress gonadotropins, linear growth velocity, and the rate of skeletal maturation. After 3 months, the subjects were randomly assigned to receive one of three daily sc doses of deslorelin: 4 micrograms/kg (n = 9), 2 micrograms/kg (n = 11), or 1 micrograms/kg (n = 9). They were treated at this dose in double blinded fashion for 15 months, after which time they resumed therapy at a dose of 4 micrograms/kg.day for an additional year. The children in the three groups did not differ in terms of chronological age, bone age, pretreatment growth rate, or Tanner stage at the onset of therapy. Similarly, there were no differences in the clinical and hormonal responses to the first 3 months of LHRHa therapy (4 micrograms/kg.day). During the 15-month period at the three different doses, the three dose groups could not be distinguished from each other in terms of pubertal stage, linear growth velocity, rate of skeletal maturation, sex steroid levels, mean LH or FSH levels, or peak FSH response to LHRH stimulation or to a dose of deslorelin. In contrast, the peak LH response to LHRH stimulation was highest in children treated with the lowest dose (1 micrograms/kg.day; P less than 0.025, by multiple analysis of variance). In addition, the peak LH response to a dose of deslorelin (the LHRHa test) was higher in children treated with 1 micrograms/kg.day than in those treated with 4 micrograms/kg.day (P less than 0.04). In summary, the LHRHa test is a sensitive means for detecting activation of the hypothalamic-pituitary-gonadal axis, and deslorelin at a dose of 1 micrograms/kg.day results in less gonadotropin suppression than a dose of 4 micrograms/kg.day.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Child; Child, Preschool; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infant; Luteinizing Hormone; Male; Puberty, Precocious; Triptorelin Pamoate

Topics: Animals; Drug Implants; Elasmobranchii; Female; Gonadotropin-Releasing Hormone; Male; Semen; Skates, Fish; Testosterone; Triptorelin Pamoate

Gonadotropin-releasing hormone (GnRH) agonists offer an alternative to surgical sterilization in prepubertal dogs, preserving ovarian and uterine functions. However, the clinical and hormonal effects of GnRH agonist application during the late-prepubertal stage remain insufficiently understood. This study aimed to investigate the clinical effect (flare-up) and hormonal changes, specifically serum progesterone (P4) and estradiol (E2) levels, in bitches treated with 4.7 mg deslorelin acetate (DA) implants (Suprelorin®, Virbac, F) during the late prepubertal period. Sixteen clinically healthy kangal cross-breed bitches, aged 7-8 months, with a mean body weight of 20.5 ± 0.8 kg, were implanted with DA. Estrus signs were monitored daily, and blood and vaginal cytological samples were collected every other day for four weeks. Cytological changes were analyzed for overall and superficial cell index. Six out of sixteen DA-treated bitches (EST group; n = 6) exhibited clinical proestrus 8.6 ± 0.6 days after implant insertion. The mean serum concentrations of P4 and E2 at the onset of estrus were 1.38 ± 0.32 ng/ml and 37.38 ± 10.07 pg/ml, respectively. Notably, all non-estrus (N-EST group; n = 10) bitches demonstrated an increase in superficial cell index, in addition to expected cytological changes observed in the EST group. On the 18th day post-implantation, the EST group exhibited a significantly higher number of superficial cells compared to the N-EST group (p < 0.001). DA implantation resulted in cytological profile alterations accompanied by a slight increase in estrogen concentrations in all dogs. However, the flare-up response exhibited significant variability, differing from that observed in adult dogs. This study highlights the importance of meticulous timing and breed-specific considerations when utilizing DA for puberty manipulation in late-prepubertal bitches. The observed cytological and hormonal changes in response to DA implants provide valuable insights, but the variability in flare-up responses warrants further investigation.

Topics: Animals; Dogs; Drug Implants; Female; Gonadotropin-Releasing Hormone; Progesterone; Sexual Maturation; Triptorelin Pamoate

Deslorelin implants are widely used in felines. Due to their prolonged duration cat breeders frequently request early implant removal. The interval between deslorelin implant removal and resumption of ovarian function in queens is unknown. The aim of this study was to evaluate the interval between the removal of a deslorelin implant and the resumption of ovarian activity in adult queens. Twenty-three queens were treated with a 4.7 mg deslorelin implant placed in the periumbilical area. In the 16 queens completing the study implants were surgically removed at 3, 6 or 9 months (n = 6, 4 and 6 queens, respectively). Queens received a GnRH stimulation test as part of their pre-treatment general and reproductive health check. Following implantation treatment, all queens in inter-oestrus-anoestrus at the time of treatment came in oestrus within 2-5 days. Starting 7-14 days following implant removal queens were checked every 1-2 weeks with reproductive ultrasonography, a vaginal smear and blood collection. The interval to resumption of ovarian function ranged from 3 to 7 weeks irrespective of treatment length and age of the queen but was longer when the implant was removed at decreasing photoperiod (p < .05). In conclusion, at least 3 weeks post-removal are needed during increasing photoperiod to achieve follicular development and oestrogen production sufficient to support oestrous behaviour in queens following removal of a 4.7 mg deslorelin implant, while this time may increase up to 7 weeks during decreasing photoperiod. Further studies are needed to assess the interval between removal of a deslorelin implant and occurrence of ovulation as well as fertility at the first oestrus after a deslorelin treatment.

Topics: Animals; Cats; Drug Implants; Estrus; Female; Gonadotropin-Releasing Hormone; Ovary; Triptorelin Pamoate

The use of deslorelin implants to control reproduction in cats is increasing but because of its prolonged duration, cat breeders often request implant removal before the end of the treatment. Assaying Anti Mullerian Hormone (AMH) concentrations might be useful to predict time of resumption of ovarian activity in deslorelin-treated queens following implant removal. In queens a minimum of 3 weeks during increasing photoperiod after implant removal has been described for resumption of ovarian activity but no information about AMH concentrations were observed for determining ovarian activity.. Sixteen queens in which deslorelin implants were surgically removed after 3, 6 or 9 months (n = 6, 4 and 6 queens, respectively) were used in this study.. A general and reproductive health check with a GnRH stimulation test were performed before the treatment. After implant removal queens were checked every 1-2 weeks with reproductive ultrasonography, a vaginal smear and blood collection to assay AMH concentrations.. AMH concentrations decreased significantly at the end of the treatment to ≤ 2.5 + 0.6 ng/ml (p ≤ 0.05) and reached a nadir at 1.9 ± 0.9 (p < 0.05) one-week post-removal. Following implant removal AMH concentrations started to rise reaching a value of 3.9 ± 0.7 ng/ml on the third week and were not different from pre-treatment levels on week 6 post-removal (5.8 ng/ml + 0.9, p ≥ 0.05). AMH values did not differ depending on duration of deslorelin treatment but were lower in adult queens (p < 0.05).. AMH assay can be a useful tool to follow resumption of feline ovarian function following a deslorelin treatment.

Topics: Animals; Anti-Mullerian Hormone; Cats; Drug Implants; Female; Reproduction; Triptorelin Pamoate

Topics: Animals; Drug Implants; Estradiol; Female; Gonadotropin-Releasing Hormone; Macaca mulatta; Progesterone; Triptorelin Pamoate

The role of anti-Müllerian hormone (AMH) and insulin-like peptide 3 (INSL3) in male infertility is not fully understood. We used the downregulated testis as a model of gonadotropin-dependent infertility. Serum testosterone and AMH concentrations were studied in five adult male Beagles implanted (day 0) with 4.7 mg deslorelin (Suprelorin®, Virbac) (DES group). Testicular expression of LH receptor (LHR) and androgen receptor (AR), AMH, type 2 AMH receptor (AMHR2), INSL3 and its receptor (RXFP2) was evaluated 112 days (16 weeks) after deslorelin treatment by qPCR and immunohistochemistry, and compared to untreated adult (CON, n = 6) and prepubertal (PRE, n = 8) dogs. Serum testosterone concentration decreased significantly by the onset of aspermia on study day 14 (four dogs) or day 21 (one dog), and was baseline on day 105 (week 15). In contrast, serum AMH started to increase only after the onset of aspermia and reached the maximum detectable concentration of the assay by day 49-105 in individual dogs. Testicular LHR gene expression in DES was lower than in CON and PRE (P < 0.0001), while AR gene expression in DES was similar to CON and significantly higher than PRE (P < 0.0001). Testicular AMH expression in DES was intermediate compared to the lowest mRNA levels found in CON and the highest in PRE (P ≤ 0.006). AMHR2 gene expression was similar between groups. AMH protein was detected in Sertoli cells only, while AMHR2 immunoreactivity was principally detected in Leydig cells which appeared to be increased in DES. INSL3 and RXFP2 gene expression was significantly downregulated in the DES testis along with noticeably weak Leydig cell immunosignals compared to CON. In conclusion, deslorelin treatment caused testicular LH insensitivity without affecting androgen sensitivity, and de-differentiation of Sertoli and Leydig cells. In DES, upregulation of the AMH-AMHR2 feed-back loop and downregulation of the INSL3-RXFP2 feed-forward loop are paracrine-autocrine mechanisms that may additionally regulate testosterone production independent of gonadotropins. Our results support AMH and INSL3 as unique biomarkers and paracrine-autocrine regulators of testis function involved in the intimate interplay between Sertoli and Leydig cells.

Topics: Animals; Anti-Mullerian Hormone; Biomarkers; Dogs; Down-Regulation; Insulin; Insulins; Leydig Cells; Male; Peptides; Proteins; Testis; Testosterone; Triptorelin Pamoate

Behavior during the estrous cycle of mares can affect their performance and therefore inhibition of cyclical ovarian activity is indicated. We hypothesized that implants containing the GnRH analog deslorelin downregulate GnRH receptors and inhibit ovulation in mares. The estrous cycles of Shetland mares were synchronized with 2 injections of a PGF

Topics: Animals; Behavior, Animal; Breeding; Drug Implants; Estrous Cycle; Female; Gonadotropin-Releasing Hormone; Horses; Luteinizing Hormone; Ovary; Ovulation; Progesterone; Receptors, LHRH; Triptorelin Pamoate

Tigers (Panthera tigris spp.) are endangered in the wild; ensuring sustainable insurance populations requires careful planning within zoological collections. In captive situations, contraceptives are often used to control breeding and ensure genetically viable populations that contain manageable numbers of animals; reversible contraceptives are ideal because they offer flexibility for breeding management. Historically, synthetic progestins, such as melengestrol acetate implants, were used in female tigers, but these are associated with an increased risk of reproductive pathology and subsequent infertility. Recent management advice to ex-situ collections has been to transition to the use of gonadotropin-releasing hormone agonists, such as deslorelin acetate implants, which do not appear to have a similar risk of reproductive pathology but are associated with highly variable reversal times in exotic felids. Using data from 917 contraceptive records in female tigers captured by the Association of Zoos and Aquariums Reproductive Management Center and the European Association of Zoos and Aquaria Reproductive Management Group's joint Contraception Database and from supplementary surveys, this study reviews the changing use of contraceptives in captive female tigers. The aim was to describe the historical and current use of contraceptives and provide a comprehensive assessment on the use of deslorelin implants, including data on product protocols, efficacy, pathology, and reversibility. This study determined that current dose, frequency, reversibility, and anatomical placement sites of deslorelin implants are highly variable, indicating that specific, readily available, unified, evidence-based recommendations on the use of deslorelin would be useful for future contraceptive use in managed tiger populations.

Topics: Animals; Animals, Zoo; Contraceptive Agents, Female; Female; Retrospective Studies; Tigers; Triptorelin Pamoate

The Association of Zoos and Aquariums Reproductive Management Center (RMC) in the US and the European Association of Zoos and Aquaria Reproductive Management Group (RMG) in Europe monitor efficacy of contraceptive products in participating institutions and use those results to inform contraceptive recommendations. This study used the joint RMC-RMG Contraception Database to analyze efficacy of deslorelin implants (Suprelorin

Topics: Animals; Animals, Zoo; Birds; Contraceptive Agents; Data Collection; Drug Implants; Female; Male; Mammals; North America; Triptorelin Pamoate

Long-acting gonadotropin-releasing hormone (GnRH) analogs, which are approved for male dogs and ferrets, have been used off-label to suppress estrus in bitches predisposed to the side effects of spaying. Health data from the past 12 years were evaluated from bitches without progestogen pretreatment that received deslorelin acetate (DA) to suppress estrus for the first time before the age of 4.5 years. The study population included 32 client-owned bitches repeatedly treated with either 4.7 mg or 9.4 mg DA implants for a period of 5.3 ± 3.4 years (range 0.5-11.3 years). Follow-up information concerning immediate side effects of DA occurring within five months after the first DA treatment (n = 23) as well as long-term side effects of sustained gonadal suppression occurring after five months up to three years (n = 2), three years up to five years (n = 2) or more than five years (n = 8) were assessed through a questionnaire. Treatment was considered successful if no major side effects requiring medical treatment occurred, which applied to 26 out of 32 (81 %) bitches. In the six remaining bitches, the following major side effects led to treatment discontinuation: persistent urinary incontinence (n = 1), reoccurring induced heat (n = 1), uterine disease (n = 3) and/or ovarian tumor (n = 3). The bitches recovered completely after surgical spaying and/or DA implant removal. Minor side effects that did not require therapy or affect animal welfare included body weight changes (n = 18), subtle behavioral changes (n = 13), induced heat (n = 12), coat changes (n = 11), pseudocyesis (n = 6), transient urinary incontinence (n = 4), and/or temporary thickening of the uterine wall with little anechogenic content (n = 2). To examine a possible causal relationship between adverse side effects and DA treatment, further studies should compare the frequency of pathologies between groups of GnRH-treated, intact and spayed bitches of similar breeds and ages. Nevertheless, DA application before the age of 4.5 years may be a means of postponing surgical spaying for several years in breeds at high risk for developing urinary incontinence. Before DA is used in bitches, owners should be fully informed regarding possible side effects.

Topics: Animals; Dogs; Drug Implants; Estrus; Female; Ferrets; Male; Reproduction; Triptorelin Pamoate

Chronic use of GnRH agonists and immunization against GnRH have been used as reversible contraceptive methods. The aim of this study was to compare the effectiveness of both treatments to inhibit reproductive function of adult bucks, in terms of strength and duration of the effects. We used 9 control untreated bucks (CON), 7 bucks treated chronically with a GnRH agonist (subcutaneous implants with 7.4 mg of deslorelin, Suprelorin, Virbac) (AGO), and another 7 bucks were immunized against GnRH (dose of 2 mL of Improvac-Zoetis with 300 μg of a synthetic incomplete analog of natural GnRH; 300 mg of diethylaminoethyl-dextran; and 2.0 mg of chlorocresol) (IMM). Testicular and sperm evaluations, testosterone concentrations, and male odor were determined from 4 wk before applying the treatments until 17 mo of their application. Scrotal circumference of CON (21.0 ± 0.1 cm) and IMM (21.2 ± 0.2 cm) was greater than that of AGO bucks (19.9 ± 0.2 cm) (P < 0.05 for each), without difference between CON and IMM bucks. Pixels' color intensity of testicular ultrasound images was not affected by treatment (general mean ± SEM: 116.0 ± 1.8). Testosterone concentration was greater in CON than AGO and IMM in months 3 and 4, greater in CON and IMM than AGO bucks in months 15 and 16, and greater in IMM than CON and AGO bucks in month 17 (P < 0.05 for all comparisons). Male odor was greater in CON (1.5 ± 0.0) than IMM bucks (1.3 ± 0.0) and greater in IMM than AGO (1.1 ± 0.0) bucks (P < 0.05 for each). Treatment negatively affected all the sperm variables: the total number of sperm in the ejaculate, sperm motility, sperm with normal morphology and sperm with integral membrane function. It was concluded that both treatments were effective in inhibiting the reproductive axis; however, neither of them produced azoospermia or decreased testosterone concentrations to undetectable levels. With both treatments, there were individual males exhibiting characteristics of fertility in all periods of the study. However, chronic use of a GnRH agonist seemed to be the most effective treatment in terms of duration and strength.

Topics: Animals; Drug Administration Schedule; Enzyme Inhibitors; Goats; Gonadotropin-Releasing Hormone; Male; Semen Analysis; Testis; Triptorelin Pamoate; Vaccines, Contraceptive

The aim of this study was to assess the effects of the deslorelin subcutaneous implant as a temporary contraceptive method in the Oryx dammah male. For this purpose, deslorelin at different doses, i.e. 14.1 mg and 9.4 mg, was subcutaneously implanted in three males (Phase 1) and one male (Phase 2) adult Oryx dammah, respectively. Quantitative behavior evaluation and androgen concentrations in feces and plasma were assessed before and after implant application. Fecal androgen concentrations observed in treated males were compared with those measured in one orchiectomized male and two females. Fecal androgen concentrations increased up to 15 days after the implant application, then progressively decreased, reaching the basal level at day150 in Phase 1. In Phase 2, levels remained high until day 60 and returned to basal level on day 120. Plasma testosterone concentration was higher on the day of implant application than three months later, but with variable ranges among males. A general increase of activity levels and hierarchical changes were observed after treatment, in accordance with hormonal variations. Despite males cohabiting with two fertile females during the observation period, no births were recorded. However, between the end of Phase 1 and the beginning of Phase 2, i.e. about 10-11 months after the first deslorelin implant, a fertile mating occurred leading to the birth of a calf. Therefore, we can hypothesize a contraceptive effect up to 10 months after the implant. Testicular histology performed on one male at the end of the Phase 2 showed no spermatogenetic activity. Our results suggest that deslorelin implant can be used to temporarily control reproduction in the Oryx dammah male. Behavior and fecal androgen measurements were useful and repeatable, non-invasive methods to monitor response.

Topics: Androgens; Animals; Antelopes; Behavior, Animal; Contraception; Contraceptive Agents; Drug Implants; Feces; Female; Male; Orchiectomy; Sexual Behavior, Animal; Testosterone; Triptorelin Pamoate

This case study evaluates the effects of a 4.7 mg deslorelin acetate implant on one male olive baboon (Papio anubis). Implantation induces transient azoospermia after which the subject was able to conceive again. Behavior was also impacted with a decrease in our proxies of aggressiveness and sexual arousal.

Topics: Aggression; Animals; Contraception; Contraceptive Agents, Male; Fertility; Male; Papio anubis; Sexual Behavior, Animal; Social Behavior; Triptorelin Pamoate

Guinea pigs are social animals that are often kept in groups regardless of their gender. Due to reproduction control and male aggressiveness prevention, surgical castration is commonly required. In the present study, we evaluated the effect of GnRH agonist implant (4.7 mg deslorelinum) on the serum testosterone concentration (T) and spermatogenesis in male guinea pigs. Twenty-four animals were divided into two groups. All animals in the first group were neutered (Group 1), animals in the second group (Group 2) were administered the implant subcutaneously and then neutered in one-month intervals. A histological examination was performed when cross sections of seminiferous tubules were assessed. Subsequently, these tubules were divided based on the most developed germ cell observed: spermatogonia, spermatocytes, round spermatids, elongating spermatids and elongated spermatids. The anticipated decrease in testosterone concentration and cessation of spermatogenesis was not achieved. Thus, the results obtained proved the inefficacy of the deslorelin implant in male guinea pigs so the alternative methods of contraception remain the methods of choice.

Topics: Animals; Gonadotropin-Releasing Hormone; Guinea Pigs; Male; Spermatogenesis; Testis; Testosterone; Triptorelin Pamoate

Topics: Animals; Cysts; Dog Diseases; Dogs; Drug Implants; Gonadotropin-Releasing Hormone; Male; Prostate; Prostatic Diseases; Prostatic Hyperplasia; Triptorelin Pamoate

The purpose of this study was to determine the optimal time for ovulation induction and artificial insemination (AI) based on the relationship between estrous behavior and ovulation in jennies. Thirty-two jennies were teased by one jackass for 1 hour per day during 46 days and estrous behaviors were recorded, while the follicular development and ovulation was examined by ultrasound. Furthermore, another 31 jennies were teased by one jackass as the teasing group (group T), which were injected with Deslorelin at 2 and 4 days after the onset of estrus, and AI was performed at 8 hours after each injection. Moreover, Ultrasound was performed on the follicle development of 23 jennies as the ultrasonography group (group U). Injection with Deslorelin when the follicle diameter ≥ 30 mm, and AI was performed at 8 hours later. The results showed that mouth clapping was the specific estrous behavior of jennies and indicated the beginning of estrus. The mean time for jennies to develop dominant follicles (≥30 mm) after the onset of estrus was 3.5 ± 1.3 days, and the mean time between the onset of estrus and ovulation was 5.1 ± 1.5 days. Estrous behaviors ended 0.5 ± 1.2 days after ovulation. After AI, there were no significant differences in ovulation (96.8% vs. 91.3%) and conception rates (40.0% vs. 38.1%) between group T and U. The optimal breeding time of jennies can be determined by jackass teasing and hastening ovulation by Deslorelin injection.

Topics: Animals; Behavior Observation Techniques; Equidae; Estrus; Female; Insemination, Artificial; Progesterone; Triptorelin Pamoate

Horses are long-day breeders and commence ovarian follicular activity during the spring. Evidence suggests that there is an endogenous circannual rhythm in mares, and it is uncertain whether hormonal manipulation during or immediately following the fall transition induces follicular development. The current study was designed to test the hypothesis that both deslorelin and naltrexone induce follicular development in late fall transitioning or anestrous mares. Five of six mares treated with deslorelin, and 4 of 6 mares treated with naltrexone, developed a pre-ovulatory-sized follicle and were inseminated. Zero of three deslorelin-control mares and 1 of 3 naltrexone-control mares were inseminated. The number of mares bred in the deslorelin treatment group was significantly higher than in the corresponding control group (

Topics: Anestrus; Animals; Female; Horses; Naltrexone; Ovulation; Pregnancy; Triptorelin Pamoate

Increased embryonic losses may be associated with inadequate progesterone (P4) concentrations in high-producing lactating dairy cattle. The objectives of the present studies were to determine if chronic administration of a gonadotropin-releasing hormone (GnRH) agonist, Deslorelin, would increase circulating P4 concentrations and subsequently increase pregnancy rates in dairy cattle. Administration of Deslorelin for 12 days increased (p < .05) luteal volume and circulating P4 concentrations in primiparous lactating dairy cows, but increased only luteal volumes in multiparous cows. Treatment with Deslorelin increased Day 45 pregnancy rates in cows as compared to untreated controls. Chronic treatment with Deslorelin in dairy cattle; (a) increased luteal volume of the primary CL, (b) induced accessory CL, (c) increased circulating P4 concentration in primiparous cows only, (d) did not lengthen the estrous cycle upon removal of treatment, and (e) increased pregnancy rates. Although luteal volume was increased in multiparous cows and circulating P4 concentrations were not with Deslorelin treatment, there was an apparent effect on pregnancy rates. This hormonal strategy may represent a suitable model to address local effects of P4 and GnRH/luteinizing hormone on uterine environment and subsequent embryonic survival.

Topics: Animals; Cattle; Cell Size; Corpus Luteum Maintenance; Female; Gonadotropin-Releasing Hormone; Luteal Cells; Pregnancy; Pregnancy Rate; Progesterone; Stimulation, Chemical; Triptorelin Pamoate

The objective of this study was to assess duration of efficacy, side effects and return to fertility following use of the 9.4 mg deslorelin implant (Suprelorin 12; Virbac) in cats, and test whether efficacy and duration of action are influenced by implantation site (interscapular vs periumbilical).. Sixteen healthy adult tom cats were checked with (1) reproductive examination, (2) gonadotropin-releasing hormone stimulation test and (3) semen collection until achievement of sterility, then with (1) and (2) only at 2, 4, 6 and 12 months, and every 6 months thereafter until treatment effect disappeared.. Serum testosterone reached basal levels by 7 days post-treatment. Semen quality improved initially then started to worsen by 1 month post-treatment and after 70 days post-treatment all cats were sterile. Early in the third month post-treatment there was a significant decrease in testicular volume and penile spikes. Testicular histology was normal upon neutering performed after resumption of fertility. No injection site lesions or treatment-related side effects were observed. There was no difference between periumbilical and interscapular placement for all criteria, but there was a trend for the decrease in testicular volume to last longer and for the regression of penile spikes to start sooner after interscapular administration. One of 16 cats did not respond to treatment. Six cats were lost at variable times during the study while fully responding to treatment. In the cats that completed the study, normal fertility was regained after 805 days, on average, but with a variable duration of effect from 750-850 days.. Treatment with a 9.4 mg deslorelin implant in male cats was effective for a period of 750-850 days, which is 1.5-2 times longer than the effect of the 4.7 mg deslorelin implant. Fertility (based on serum testosterone production and the presence of penile spikes) was regained at the end of the study. Placing implants in the intrascapular vs periumbilical location did not affect duration of suppression of testosterone production. The interscapular location may be characterised by a better efficacy, although further studies are needed to clarify this issue.

Topics: Animals; Cats; Drug Implants; Fertility; Male; Scapula; Semen Analysis; Testis; Triptorelin Pamoate; Umbilicus

The aim of this study was to investigate the relationship of progesterone (P) and luteinizing hormone (LH) during recognition and establishment of pregnancy in the gilt. Therefore, the effects of eliminating episodic LH pulses on P patterns were determined during early pregnancy. To this end, a slow-release GnRH implant deslorelin was used for GnRH down-regulation. A group of gilts (GnRHa, n = 8) was implanted with the GnRH-agonist on Day 11 of pregnancy, while a control group (C, n = 5) was treated with a non-impregnated placebo implant. Blood was collected via a vena cava caudalis catheter at 10-min intervals for 8 hr on Day 16 and 21 of pregnancy. As expected, the GnRH implant reduced LH secretion (p < 0.01) and abolished LH pulses completely at Day 16 and Day 21 of pregnancy. On Day 16, there was no difference in P levels between the treatments. However, on Day 21, the GnRH-agonist treatment led to significantly increased P concentrations (p < 0.01) compared with the control gilts. Progesterone was secreted in a pulsatile manner in both treatment groups and no relationship between LH pulsatility and P pulsatility was observed. In conclusion, abolishment of LH pulsatility did not affect the pulsatile pattern of P secretion but led to an unexpected overall increase in P on Day 21 of pregnancy; this effect was delayed and occurred 10 days after commencing treatment with the GnRH depot agonist. The elevation of P on Day 21 of pregnancy in the GnRHa group suggests either a reduced negative feedback effect or an increased autocrine response by the corpora lutea.

Topics: Animals; Corpus Luteum; Drug Implants; Estradiol; Female; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Luteolysis; Ovarian Follicle; Ovary; Pregnancy; Progesterone; Swine; Triptorelin Pamoate

This study describes the first case of contraception within a captive elasmobranch breeding programme where an implant of Suprelorin, containing a long-acting gonadotrophin-releasing hormone (GnRH) analogue Deslorelin, was implanted in an eagle ray Aetobatus ocellatus, which successfully halted breeding.

Topics: Animals; Breeding; Contraception; Elasmobranchii; Endangered Species; Female; Gonadotropin-Releasing Hormone; Triptorelin Pamoate

Housing bachelor groups is a necessary aspect of the care and husbandry of non-breeding individuals in zoological collections. Intraspecific aggressive behaviors may occur in this setting despite management strategies designed to mitigate these behaviors. Androgens (including testosterone) are associated with aggression in male species and interventional techniques to alter the animals' physiology to modify aggressive behavior are sometimes required. When agonistic behavior and physical aggression in two mature male Amur leopards housed together at Tayto Park escalated, despite all strategic management involvements, further intervention to moderate aggression was required. The gonadotropin-releasing hormone (GnRH) agonist, deslorelin, has been found to be effective in reducing androgens in domestic and non-domestic carnivores. We hypothesized that deslorelin's suppressive effect on hypothalamic-pituitary-gonadal axis would mitigate intraspecific aggression in two male intact leopards. Behavioral observations were carried out pre- and post-implant implantation of 9.4 mg deslorelin implant. The frequency of agonistic/aggressive behaviors for both leopards declined significantly (p < 0.05), as did marking behaviors post-implantation (p < 0.001). The insertion of deslorelin implants in two male intact leopards demonstrating increased frequency and severity of aggressive behaviors resulted in a reduction of the frequency of these behaviors. Deslorelin implantation should be considered for management of interspecific aggression of intact male leopards in bachelor groups.

Topics: Aggression; Animals; Animals, Zoo; Drug Implants; Enzyme Inhibitors; Gonadotropin-Releasing Hormone; Male; Panthera; Triptorelin Pamoate

Contraception is increasingly used to manage breeding opportunities in conservation-dependent species. This study aimed to determine the efficacy, duration of effect, optimal dose and potential side effects of Suprelorin contraceptive implants in Tasmanian devils, for use in the conservation breeding program. In our pilot study, Suprelorin was found to effectively suppress oestrous cycles in female devils, yet caused a paradoxical increase in testosterone in males. Therefore, we focussed on females in further trials. Females received one (n=5), two (n=5) or no (n=5) Suprelorin implants, with quarterly gonadotrophin-releasing hormone (GnRH) challenges used to test pituitary responsiveness over two breeding seasons. Both Suprelorin doses suppressed pituitary responsiveness for at least one breeding season, with a reduced effect in the second. There was a dose-response effect on duration rather than magnitude of effect, with high-dose devils remaining suppressed for longer than low-dose animals. There were no apparent negative effects on general health, yet captivity and contraception together may cause weight gain. Suprelorin contraceptive implants are now routinely used in the Save the Tasmanian Devil Program insurance metapopulation to meet the aims of maintaining genetic and behavioural integrity by controlling individual reproductive contributions in group housing situations.

Topics: Animals; Breeding; Conservation of Natural Resources; Contraceptive Agents; Dose-Response Relationship, Drug; Endangered Species; Estrous Cycle; Female; Male; Marsupialia; Pituitary Gland; Reproduction; Testosterone; Triptorelin Pamoate

The objective of the present was to determine the effect of long-term release GnRH agonists "deslorelin" on suppression and restoration of testicular and accessory sex glands functions, and expression of HSP in testes of adult male rats. A group of twenty-eight male rats and fifty-six female rats were kept for eleven months. The male rats were subdivided into treatment (n = 18; deslorelin, an analogue of GnRH, 4.7 mg, S.C; six months) and control (n = 10; untreated), and the adult female rats were introduced with either treatment or control male rats at the 2nd, 6th and 11th months post implant insertion. At 6th month of deslorelin implants insertion, six male rats from treatment and five rats from control group were sacrificed. The remaining (twelve treatment and five control) male rats were sacrificed at 11 months. The testicular dimension were measured monthly in both treatment and control rats. The blood samples were collected for testosterone and HSP70 antibody, whereas, the testes and accessory glands were isolated for histological examination at each sacrificial time. The results showed that testicular dimension were significantly lesser in treatment group until 9 months post treatment. HSP70 protein expression was negligible at 6 months in treatment group but its intensity increased in spermatids 11 months of treatment similar to control group. Significantly lower testosterone concentrations with poor semen quality, and smaller litter size were observed in treatment group. The histological picture of accessory sex glands and seminiferous tubules shown a variable integrity in treatment group than control at 6 months implant insertion. In conclusion, the subcutaneous application of 4.7 mg of the GnRH-analogue deslorelin represents a practicable, like in the female rats, method to suppress testicular, accessory sex glands functions, testicular HSP expression and fertility in male rats. Moreover, the suppressive effects of deslorelin, continued until 11th months after removal of the implant.

Topics: Animals; Delayed-Action Preparations; Female; Fertility; Gonadotropin-Releasing Hormone; HSP70 Heat-Shock Proteins; Litter Size; Male; Organ Size; Pregnancy; Pregnancy Rate; Rats; Reproductive Control Agents; Semen Analysis; Testis; Testosterone; Triptorelin Pamoate

In captive breeding programs, it is becoming increasingly important to maximize the retention of genetic diversity by managing the reproductive contribution of each individual, which can be facilitated through the use of selective contraception. This becomes critical when captive populations are held for several generations, and managers must prevent the confines of housing space and financial support from compromising genetic integrity. For example, the Tasmanian devil insurance population, established in 2006, is strategically managed to equalize founder representation. This becomes difficult when devils are housed in large groups in free-range enclosures (FREs). This study examined the efficacy, duration and potential side effects of Suprelorin

Topics: Animal Husbandry; Animals; Australia; Body Weight; Contraceptive Agents; Drug Implants; Endangered Species; Enzyme Inhibitors; Feeding Behavior; Female; Marsupialia; Reproduction; Seasons; Triptorelin Pamoate

Gonadotropin-releasing hormone (GnRH) regulates gonadotropin secretion. We previously demonstrated that the expression of annexin A5 (ANXA5) is stimulated by GnRH in gonadotropes and has a significant role in gonadotropin secretion. It is therefore of interest to know whether other members of the ANXA family, which consists of twelve structurally related members, are also regulated by GnRH. Therefore, the expression of all annexins was examined in LβT2 gonadotrope cells. ANXA4, A5, A6, A7 and A11 were detected in LβT2 cells. The expression of ANXA5 and A1 mRNA was stimulated by a GnRH agonist. An increase in ANXA1 protein by this agonist was demonstrated by western blotting. Immunohistochemistry showed that ANXA1 was present in the nucleus and to a lesser extent in the cytoplasm of some rat pituitary cells. The GnRH agonist induced translocation of ANXA1 to the periphery of LβT2 cells. The presence of ANXA1 in gonadotropes and its increase upon GnRH agonist treatment were confirmed in a primary pituitary cell culture. ANXA1 expression was also demonstrated in the ovary, the testis, the thyroid gland and the pancreas in a different manner to that of ANXA5. These data suggest that ANXA1 is a novel GnRH target gene in gonadotropes. ANXA1 also may be a target of local GnRH in peripheral tissues and may have a different role than that of ANXA5.

Topics: Animals; Annexin A1; Annexins; Cell Line; Female; Gene Expression; Gonadotrophs; Gonadotropin-Releasing Hormone; Immunohistochemistry; Male; Mice; Pituitary Gland; Rats, Wistar; RNA, Messenger; Triptorelin Pamoate

Hormonal contraception is being increasingly used to manage captive animals in zoological collections. Many of the animals placed on contraception are of genetic importance within captive breeding programs; therefore, it is imperative that the application of contraceptive products minimize potential side effects and facilitate a return to fertility if required. Deslorelin acetate implants (Suprelorin®) are one example of a hormonal contraceptive that is frequently used in captivity as they are easy to use and effective in most species. It is hypothesized that removing implants may hasten reversal of contraception treatment; therefore, placement in a location where they can easily be recovered is advocated. In this report, the efficacy and safety of Suprelorin implants placed in their recommended site between the scapulae is compared with alternative placement sites where implants can more easily be located for removal. Using the European Association of Zoos and Aquariums (EAZA) Group on Zoo Animal Contraception (EGZAC) Contraception Database, rates of success, failure, and reversal in 561 records of Suprelorin use in European collections are compared. Of these, 357 have information relating to the location of implant placement. When correctly applied, rates of efficacy were high (>99%) irrespective of placement site. Rates of reversal were 33.3% higher in alternative placement sites, although in most cases it is unknown whether implants were removed or not. In conclusion, the placement of Suprelorin implants in alternative sites does not negatively affect the efficacy, facilitating at the same time implant removal, minimizing potential side effects, and reducing reversal time, allowing for effective use in captive conservation breeding programs.

Topics: Animals; Animals, Zoo; Contraception; Contraceptive Agents; Drug Implants; Europe; Female; Triptorelin Pamoate

The hypothesis in this study was continuous treatment of stallions with the GnRH agonist deslorelin inhibits reproductive functions. A 2-week pre-experimental period was followed by an 11-week deslorelin implant treatment. Stallions received 4.7 (D1, n = 7), or 18.8 mg deslorelin (D2, n = 5) or remained untreated (C, n = 5). Libido, sperm motility, membrane integrity, DNA fragmentation, estrogen receptors, basal plasma testosterone and Anti Muellerian hormone (AMH) concentrations were evaluated once weekly during the treatment period. The testosterone response to the GnRH agonist buserelin and hCG was evaluated twice. In Week 2, stallions in Group C but not Groups D1 and D2 responded to buserelin with testosterone release (P < 0.001), while in Week 9, stallions in Group C and D1 but not D2 released testosterone after buserelin administration (group P < 0.01, week P = 0.01). Stallions of all groups responded to hCG with testosterone release at both times of hCG administration (P < 0.001). The AMH concentration was similar in all groups. Deslorelin thus reduced pituitary responsiveness to GnRH but only with a large dose and this effect persisted for several weeks. Total sperm count increased transiently with the D2 treatment but not in stallions of the D1 and C groups after implant insertion (time P < 0.01, time x group P < 0.001). The percentage of ESR1-positive spermatozoa decreased transiently in Group D2 (time P < 0.01, time × group P < 0.01). There was no difference among groups at any time during the study in percentage of motile and membrane-intact spermatozoa and sperm with DNA fragmentation. In conclusion, deslorelin implants modulate pituitary function in stallions but not to an extent that affects testicular function.

Topics: Animals; Drug Implants; Enzyme Inhibitors; Horses; Male; Semen; Semen Analysis; Spermatogenesis; Testosterone; Triptorelin Pamoate

The objective of this study was to assess the efficiency and clinical safety of postnatal administration of a GnRH agonist on canine puberty postponement. Sexual steroids and histological gonadal changes were also described. Twenty-four littermate puppies were randomly assigned to: Deslorelin acetate 18.8 mg sc (DESLO; n = 12) or Placebo: sc (PLACE; n = 12) postnatally. The dogs were clinically and endocrinologically followed up until puberty when they were gonadectomized and their gonads histomorphometrically studied. Deslorelin postponed the age of puberty (72.7 ± 4.8 vs. 35.8 ± 1.9 weeks; P < 0.01) in these dogs. At the time of this submission, 3 DESLO dogs (108 weeks old) remain non-pubertal. All dogs concluded growing at a similar age (29.75 ± 2.44 vs. 29.25 ± 0.90 weeks; P > 0.1) independently of their group and pubertal status. None of the females had side effects while the 2 non pubertal DESLO males presented bilateral cryptorchydism. All the bitches ovulated at puberty (P > 0.1) and the 2 DESLO that were mated became pregnant. Deslorelin postponed basal serum sexual steroids up to puberty in both genders (P < 0.01). The histomorphometrical study of the testes revealed that the tubular diameter (P < 0.05), germinal epithelium height and composition (P < 0.01) were decreased in DESLO group. Ovarian structures did not differ between treatments (P > 0.05). It was concluded that postnatal deslorelin decreased sexual steroids reversibly postponing puberty in both genders without side effects in bitches and causing 2/6 of cryptorchydism and impairment of testicular histomorphometry in male dogs.

Topics: Aging; Animals; Animals, Newborn; Contraception; Cryptorchidism; Dog Diseases; Dogs; Female; Gonadotropin-Releasing Hormone; Male; Ovary; Ovulation; Pregnancy; Sexual Maturation; Testis; Testosterone; Triptorelin Pamoate

Aim of the study was to examine the effect of deslorelin on uterine tissues of eleven pre-pubertal bitches aged 4.2 ± 0.6 m. Implants containing placebo (sodium chloride 0.9%; n = 4, G I), 4.7 mg (n = 3, GII) or 9.4 mg (n = 4, GIII) deslorelin acetate (Suprelorin

Topics: Animals; Dogs; Drug Implants; Estradiol; Estrus; Female; Gonadotropin-Releasing Hormone; Kisspeptins; Progesterone; Receptors, G-Protein-Coupled; Receptors, Steroid; Triptorelin Pamoate; Uterus

OBJECTIVE To evaluate effects of administration of a 4.7-mg deslorelin acetate implant on egg laying in healthy cockatiels (Nymphicus hollandicus). ANIMALS 52 cockatiels. PROCEDURES 26 breeding pairs (a female and its respective male in each pair) were selected on the basis of their history of egg laying. Female birds were sedated and received a 4.7-mg deslorelin acetate implant (n = 13) or placebo implant (13) in the subcutaneous tissues between the scapulae. Male and female birds of each breeding pair were placed in separate but adjacent cages. Birds were exposed to 16 hours of light and 8 hours of darkness. A nest box was placed in cages of female birds to stimulate reproductive activity. Egg production and quality were monitored daily for 365 days. RESULTS Deslorelin acetate implants significantly suppressed egg laying in cockatiels, compared with effects for the placebo implants. Eleven of 13 placeboimplanted birds laid eggs between 12 and 42 days after implantation. None of the deslorelin-implanted birds laid eggs within 180 days after implantation, and only 5 of 13 deslorelin-implanted birds laid an egg during the study period (first egg laid between 192 and 230 days after implantation). No differences in egg quality or number of eggs per clutch were observed between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE Insertion of a 4.7-mg deslorelin acetate implant suppressed egg laying in healthy cockatiels for at least 180 days. Studies are necessary to evaluate effects of a deslorelin acetate implant in other avian species or in association with reproductive disorders.

Topics: Animals; Breeding; Cockatoos; Drug Implants; Female; Male; Oviposition; Ovum; Reproduction; Triptorelin Pamoate

Anti-Müllerian hormone (AMH) is widely used in human medicine to non-invasively estimate the size of the ovarian follicle reserve and to predict the ovarian response to gonadotropin stimulation in the context of assisted reproductive technologies (e.g., IVF). These applications of AMH testing have recently expanded to non-human mammals, with production animals, such as cows, goats and sheep being the primary focus of AMH research. However, few investigations have involved exotic species, and in particular carnivores. In this study, we measured AMH concentrations (0.078-3.078ng/mL) in archived serum samples that had been collected from 36 adult female cheetahs across their reproductive lifespan (2-15years of age). Similar to other mammals, AMH concentration in cheetahs declined with age, and its variability among females of the same age was considerable. The rates at which AMH declined over time in individual cheetahs were also highly variable. Five cheetahs had been contracepted with the long-acting GnRH agonist deslorelin for 6-18months prior to sample collection, and their AMH concentrations were relatively low compared to untreated females. In this first study of AMH in an exotic carnivore, the findings demonstrate that the age-associated decline in AMH is highly variable and that deslorelin appears to suppress AMH concentration in serum. Owing to the increased use of assisted reproductive technologies in ex situ populations of threatened and endangered species, such as cheetahs, the present study's findings will need to be taken into consideration if AMH is to be used successfully to optimize breeding management decisions in exotic species.

Topics: Acinonyx; Aging; Animals; Anti-Mullerian Hormone; Female; Triptorelin Pamoate

In Europe, the yellow-bellied slider (Trachemys scripta sp.) is a non-native species in competition with native freshwater turtles. Research on contraception could be useful to control the captive population. Identifying a method of contraception in chelonians would potentially help to control aggression in other chelonian species. The objective of the current study was to evaluate the effects of a single 4.7-mg deslorelin acetate implant on plasma testosterone concentrations in yellow-bellied sliders (Trachemys scripta sp.). Eleven adult male yellow-bellied sliders were used for the study. Males from the treatment group (n = 6) received a 4.7-mg deslorelin acetate implant, whereas males from the control group (n = 5) did not receive any treatment. All individuals were housed under the same environmental conditions. Testosterone plasma concentrations of the control group and the treatment group were measured at six time points (T0-T6) between April and September. No difference between the control group and the deslorelin treatment group was observed at T0, T2, T3, T4, T5 or T6. However, mean plasma testosterone concentration was significantly higher in the treatment group than in the control group at T1. This suggests that treatment with a 4.7-mg deslorelin acetate implant has a transient stimulatory effect on the anterior pituitary in yellowbellied sliders without a negative feedback on testosterone production. Further studies with a higher dosage of deslorelin acetate are needed to draw conclusions on its contraceptive effect.

Topics: Animals; Drug Implants; Enzyme Inhibitors; Male; Testosterone; Triptorelin Pamoate; Turtles

The goals of this study were as follows: (Experiment 1) to examine the basic capability of canine corpora lutea (CL) to respond to GnRH by assessing expression of gonadotropin-releasing hormone receptor (GnRH-R) in luteal samples collected throughout the luteal lifespan from non-pregnant dogs, and (Experiment 2) to investigate the effects of pre-pubertal application of the GnRH agonist deslorelin acetate on luteal function following the first oestrus. Mature CL were collected during the mid-luteal phase (days 30-45) from treated and control bitches. Transcript levels of several factors were determined: estrogen receptors (ESR1/ERα, ESR2/ERβ), progesterone (P4)-receptor (PGR), prolactin receptor (PRLR), PGE2-synthase (PTGES) and PGE2 receptors (PTGER2/EP2, PTGER4/EP4), vascular endothelial growth factor (VEGFA) and VEGF receptors (VEGFR1 and VEGFR2), cyclooxygenase 2 (COX2/PTGS2), steroidogenic acute regulatory protein (STAR) and 3β-hydroxysteroid dehydrogenase (3βHSD). Additionally, levels of Kisspeptin 1 (Kiss1) and its receptor (KISS1-R) were evaluated. Although generally low, GnRH-R expression was time dependent and was elevated during early dioestrus, with a significant decrease towards luteal regression. In deslorelin-treated and control dogs, its expression was either low or frequently below the detection limit. EP2 and VEGFR1 were higher in the treated group, which could be caused by a feedback mechanism after long-term suppression of reproductive activity. Despite large individual variations, 3βHSD was higher in the deslorelin-treated group. This, along with unchanged STAR expression, was apparently not mirrored in increased luteal functionality, because similar P4 levels were detected in both groups. Finally, the deslorelin-mediated long-term delay of puberty does not have negative carry-over effects on subsequent ovarian functionality in bitches.

Topics: Animals; Corpus Luteum; Dogs; Female; Kisspeptins; Receptors, Cell Surface; Receptors, LHRH; Receptors, Steroid; Sexual Maturation; Triptorelin Pamoate

Objectives Gonadotropin-releasing hormone (GnRH) agonists like deslorelin are being increasingly used in tom cats for their efficacy in controlling reproductive behaviour and fertility. Deslorelin implants have been widely available in Europe since 2008. Little, if anything, is known about the interval between treatment and onset of sterility, as well as semen quality, after treatment in tom cats. The purpose of this study was to investigate semen quality and interval to sterility in tom cats treated with a 9.4 mg deslorelin implant. Methods Fifteen healthy adult tom cats were treated with a 9.4 mg deslorelin implant (Suprelorin 12). For each cat, semen collection and a GnRH stimulation test (intramuscular administration of 50 μg gonadorelin [Fertagyl], followed by blood sampling 1 h later, to assay serum testosterone) were performed on the first consultation and then repeated every 15 days until complete sterility was achieved. Semen collection was performed by introducing a 14 cm, open-end feline catheter (Argyle) 9 cm into the distal urethra 10 mins after sedation by intramuscular injection of 100 μg/kg medetomidine (Domitor). Results Semen collection was not successful in all cats at each attempt. In the first month after treatment, the semen of only four cats could be evaluated, while the semen of eight cats could be evaluated during the second and third months of the study. Semen quality (ejaculate volume, progressive motility and morphological abnormalities) improved slightly during the first 19-25 days in 2/4 cats, and in 1/4 cats motility was still very high (80%) 25 days post-treatment (PT), but we have no data regarding fertility prior to treatment in this cat. The last cat never produced spermatozoa. Subsequently, semen quality gradually worsened in all cats from 30 days onwards. At 70 days PT, one cat was still potentially fertile. After 72 days all cats were sterile. Conclusions and relevance Semen quality increased slightly in treated cats during the first month after treatment, and then gradually decreased over the following months. Complete sterility was reached within 40-72 days following implantation.

Topics: Animals; Cat Diseases; Cats; Contraception; Contraceptive Agents, Male; Drug Implants; Infertility; Infertility, Male; Male; Semen; Semen Analysis; Sexual Behavior, Animal; Triptorelin Pamoate

Effective and humane management strategies for coyotes (Canis latrans) remain elusive. We hypothesised that exposure to a high dose of a gonadotrophin-releasing hormone (GnRH) agonist would cause prolonged suppression of the reproductive axis. Two groups of male coyotes were administered 47mg deslorelin in the form of either five 9.4-mg controlled-release Suprelorin (Peptech Animal Health, Macquarie Park NSW, Australia) implants (n=3) or 10 4.7-mg implants (n=5). In the first group, deslorelin suppressed plasma LH, testosterone and testes volume in two of three coyotes for three breeding seasons. In the second group, two of five deslorelin-treated coyotes had no sperm production after 1 year and plasma LH, FSH, testosterone and testes volume were suppressed. Although plasma gonadotropins and testosterone were suppressed in three treated coyotes in group two, testes volume and sperm production were evident. Because the duration of suppression differed among individual coyotes, we further hypothesised that a variation in deslorelin release underlay the variability. To test this, we analysed in vivo plasma profiles of deslorelin concentrations. These profiles suggested that deslorelin concentrations >100 pg mL

Topics: Animals; Contraceptive Agents, Male; Coyotes; Drug Implants; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Male; Reproduction; Semen; Sperm Count; Testis; Testosterone; Time Factors; Triptorelin Pamoate

Effect of a GnRH-agonist (deslorelin) was studied on reproductive function and ovarian luteinizing hormone receptor (LHR) and follicle stimulating hormone receptor (FSHR) expression in prepubertal female cats that were either implanted with 4.7-mg deslorelin (implanted: n = 6) or not (controls: n = 18) or ovariohysterectomized at prepubertal age (prepubertal OVH: n = 6). Body weights, fecal estradiol, and sexual behavior of implanted and control cats were monitored for 48 weeks followed by collection of ovaries and uteri. Ovaries and uteri were collected from control cats at follicular, luteal, and inactive stage (n = 6/group) and from prepubertal OVH cats at prepubertal age. Ovaries and uteri were analyzed for anatomical/histological characteristics. Ovaries were also analyzed for LHR and FSHR expression. Statistical analysis showed higher (P ≤ 0.05) body weight in control than implanted cats only during 22nd to 26th weeks of the study. Estrus was observed in control cats only. Deslorelin reduced (P ≤ 0.05) ovarian weight and number of antral follicles but did not affect endometrial thickness and gland diameter. However, myometrial thickness of implanted cats was significantly lower than control cats at follicular and luteal stage. Ovarian LHR mRNA expression was lower (P ≤ 0.05) in implanted cats than control cats at follicular stage. FSHR mRNA and LHR protein expression did not differ among the three groups. FSHR protein expression was lower (P ≤ 0.05) in prepubertal OVH cats and was not affected by deslorelin. In conclusion, deslorelin suppresses reproductive function in prepubertal female cats for at least 48 weeks possibly through a change in the ovarian mRNA expression of LHR.

Topics: Animals; Cats; Drug Implants; Female; Gene Expression; Ovary; Receptors, FSH; Receptors, LH; Sexual Maturation; Triptorelin Pamoate

Over the last 40 years, researchers have explored methods to non-surgically suppress fertility in animals. Immunocontraception has been used to control wildlife populations but does not confer long-term immunity. The gonadotropin-releasing hormone (GnRH) agonist deslorelin, formulated as an implant to provide 6-month to 1-year suppression of fertility in male dogs, is available commercially in some countries. Neither of these approaches provide permanent sterility. A single-dose, permanent treatment would be a valuable tool in dog and cat population control. The Michelson Prize and Grants (MPG) programme was initiated "to eliminate shelter euthanasia of healthy, adoptable companion animals and reduce populations of feral and free-roaming cats and dogs" offering a $25 million US prize for a non-surgical sterilant that is effective as a single treatment in both male and female dogs and cats. Michelson Prize and Grants programme has offered US $50 million in grant money for research and has attracted scientists worldwide. Approaches under study include gene therapy, small interfering RNA to inhibit reproductive targets and delivery of cytotoxins to pituitary gonadotrophs or GnRH producing neurons in the hypothalamus. Research in implant technology that could deliver compounds over an animal's lifetime is also underway. Details of funded grants and results to date can be found at: http://www.michelsonprizeandgrants.org/michelson-grants/research-findings. The next steps are translating the most promising research into products. The Alliance for Contraception of Cats and Dogs (ACC&D) is helping to research practical methods of marking sterilized animals to avoid costly retreatment and population modelling that will help guide field workers in use of resources for sterilization programmes.

Topics: Animals; Awards and Prizes; Cats; Contraception; Contraception, Immunologic; Contraceptive Agents; Cytotoxins; Dogs; Drug Implants; Female; Gene Silencing; Gonadotropin-Releasing Hormone; Infertility; Male; Population Control; Research Support as Topic; RNA, Small Interfering; Sterilization, Reproductive; Triptorelin Pamoate

Objectives The present study investigated the effect of contraceptive treatment with deslorelin acetate on in vitro embryo production and oocyte recovery in domestic queens. Methods Twenty-one mature domestic cats were used. Eleven queens (treated group) and one tom were kept in an experimental cattery, and 10 queens were privately owned (control group). When in interestrus or diestrus (day 0) a deslorelin acetate implant (Suprelorin, 4.7 mg/animal) was inserted into the subcutaneous tissue of the interscapular region in all queens in the treated group. After 6 months of treatment, all animals were ovariohysterectomized, and the ovaries were used for in vitro embryo production. Percentage of cleavage was determined 18 h after oocyte insemination and blastocyst formation was assessed on the eighth day of culture. The rate of cumulus-oocyte complexes (COCs) recovery was analyzed by an unpaired t-test. The cleavage and blastocyst rates were expressed as percentages and analyzed by Fisher's exact test. All analyses were performed using GraphPad Prism v5.0, with P <0.05 set as the level of significance. Results In the treated group, we recovered 8.3 ± 1.15 grade I COCs per queen; the cleavage rate was 60% and the blastocyst rate was 36%. In the control group, we recovered 18.4 ± 3.21 grade I COCs per queen; the cleavage rate was 55.97% and the blastocyst rate was 34%. Forty percent of treated females did not produce any blastocysts. In the treated group, we observed a significant decrease in COC recovery. Although there was no significant difference in cleavage and blastocyst rates between groups, 40% of treated females did not produce any blastocysts. Conclusions Recovery of grade I COCs is negatively affected by deslorelin treatment in domestic cats. Regarding embryo production, new studies are still necessary to evaluate the success of this technique owing to the individual effect caused by deslorelin acetate.

Topics: Animals; Blastocyst; Cats; Female; Fertilization in Vitro; Oocyte Retrieval; Oocytes; Triptorelin Pamoate

Objectives The purpose of this study was to assess efficacy of deslorelin, a gonadotropin-releasing hormone (GnRH) agonist marketed in Europe for the control of male dog reproduction, for the postponement of puberty in queens. Methods Nine prepubertal queens aged 3-9 months were selected for this study; their general and reproductive health was checked through clinical, haematological, vaginal cytology and hormonal tests. Following treatment with a 4.7 mg deslorelin implant, each cat received a monthly clinical examination and blood was collected for hormonal assay every third month. Cats were monitored for 14.1 ± 5.2 (range 7-23) months. Results All cats were in good body condition and normal health prior to treatment. Their health status remained unchanged throughout the study and no significant variation was observed with regard to serum progesterone or oestradiol. Seven days post-treatment, 1/9 queens showed signs of heat, and one other queen showed complete vaginal keratinisation. No other signs of heat were subsequently observed in any other queen. Five queens were lost during the study after 7, 7, 16, 17 and 18 months of observation (during which time they did not show signs of heat). By the end of the study, no sign of puberty was observed in the four remaining queens at 21-36 months of age. Conclusions and relevance A 4.7 mg deslorelin implant was able to suppress the feline pituitary-gonadal axis, leading to postponement of puberty for up to 21-36 months in the four queens that completed the study. Deslorelin can be considered as a safe method to postpone puberty in queens.

Topics: Animals; Cats; Contraception; Drug Implants; Enzyme Inhibitors; Female; Gonadotropin-Releasing Hormone; Sexual Maturation; Triptorelin Pamoate

Lower urinary tract symptoms are not only a serious health problem but also a substantial sociologic issue affecting human beings and companion animals. Estrogen deficiency is considered an etiologic factor of urinary incontinence in postmenopausal women and spayed female dogs. However, insufficient effectiveness of hormonal therapy has caused an intensive search for new therapeutic options. GnRH analogs have positive clinical effects in neutered female dogs suffering from incontinence, but the mechanism of action is not known. The aim of our study was to determine the effect of long-acting deslorelin acetate on the spontaneous activity of urinary bladder sections from a rabbit model of long-term estrogen deprivation. The study was conducted on 21 female New Zealand White rabbits divided into the following groups: control group, ovariohysterectomized (OHX) group, and ovariohysterectomized group given a deslorelin acetate implant. Urinary bladders were excised immediately after sacrifice, and the spontaneous activity of dorsal and ventral strips of the bladder body was examined in organ bath chambers. The amplitude and frequency of the spontaneous contractions were evaluated. Most of the sections developed spontaneous activity. Ovariohysterectomy caused a decrease in the amplitude of spontaneous contractions of the tissues obtained only from the dorsal part of the bladder body. After OHX, the frequency was higher compared with the control group in both parts of the bladder. Deslorelin acetate did not significantly affect the spontaneous contraction amplitude but caused a decrease in the frequency in the dorsal and ventral parts of the bladder. In conclusion, long-term changes in the levels of hormones and other regulatory substances associated with the reproductive system are related to altered spontaneous activity of the urinary bladder, which may impact the symptoms of urgency and incontinence appearing in women after menopause and in female animals after gonadectomy. However, long-acting deslorelin acetate partially reverses the effect of OHX on the spontaneous activity of the bladder. This process might underlie the positive effects of GnRH analogs in incontinent spayed female dogs.

Topics: Animals; Female; Hysterectomy; Models, Animal; Muscle Contraction; Ovariectomy; Rabbits; Triptorelin Pamoate; Urinary Bladder

The effects of deslorelin acetate use in inducing ovulation need to be clarified to improve the results of equine embryo transfer. The mRNA abundance for angiogenic factors and LH receptor (LHR) in corpus luteum (CL) was studied in mares with natural (control group [CG]) and induced ovulation with deslorelin acetate (treatment group [TG]; follicles: ≥ 35 mm). Transrectal ultrasonography was used to verify the ovulation day, and on Days 4, 8, and 12 after ovulation (Day 0), CL samples were obtained through ultrasound-guided biopsy. The messenger RNA expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and LHR genes were analyzed by real-time polymerase chain reaction. A positive correlation was observed between VEGF and LHR (P < 0.00001, r = 0.78), and it was possible to detect higher LHR expression in the TG than in the CG on Day 4 (P < 0.05). Moreover, this expression was higher on Days 4 and 8 than on Day 12 in the TG. Basic fibroblast growth factor was also expressed in luteal tissue on all days for both groups; however, these differences were not significant. In conclusion, deslorelin acetate was effective for the induction of ovulation in mares, resulting in higher expression of LHR, especially on the fourth day after ovulation. In addition, VEGF expression was influenced by induced ovulation, with a lower level on Day 12, which is expected in nonpregnant mares.

Topics: Animals; Corpus Luteum; Female; Fibroblast Growth Factor 2; Gene Expression; Horses; Ovulation; Ovulation Induction; Receptors, LH; RNA, Messenger; Triptorelin Pamoate; Vascular Endothelial Growth Factor A

The aim of this study was to examine the long-term effect of a 4.7-mg deslorelin GnRH analog implant on ovarian function in the prepubertal female rabbit. Seven female rabbits (group 1) were treated with the implant at the age of 60 days. The implant was inserted subcutaneously in the umbilical region. Two animals (group 2) were not treated and served as a control group. The vulva of all 9 animals was examined for the presence of typical cyclical changes, additionally the occurrence of mounting behavior was recorded. Ovarian function was checked by administration of a short-acting GnRH agonist to induce ovulation and pseudopregnancy (0.8 μg of buserelin per animal intramuscularly). Ten days after each treatment with buserelin, blood was collected for progesterone measurement to confirm pseudopregnancy. After implant insertion, the first blood collection (Day 10) was done without preceding induction of ovulation to screen for implant induced ovulation and pseudopregnancy. The implant was in situ for 273 days, and during this time span, 12 attempts of induction of ovulation were carried out in intervals of 21 days, beginning at the age of 81 days. Afterward, it was removed under local anesthesia and 3 further inductions of ovulation by the same scheme were conducted. The insertion of the implant led to the establishment of a pseudopregnancy in 2 of 7 animals; the remaining 5 animals did not show elevated progesterone values. Attempts to induce ovulation by administration of the short-acting GnRH analog while the slow-release GnRH analog implant was in place were not successful in treated animals, and progesterone concentrations were basal. The effect was reversible as ovulation could be induced in 2 subsequent cycles in all animals by the third induction of ovulation after implant removal. Induction of ovulation in control animals at the age of 110 and 131 days resulted in elevated progesterone levels after 10 days. No adverse side effects could be observed in implant-treated animals. The typical red coloration of the vulva could be seen in group 2 and after implant removal in group 1. The results suggest that in 5 of 7 rabbits, puberty was delayed by the treatment with the 4.7-mg deslorelin slow-release analog until the implant had been removed. In the other animals, the treatment induced an initial flare-up phenomenon. Afterward, the treatment could reversibly suppress ovarian function in all 7 treated animals.

Topics: Animals; Buserelin; Delayed-Action Preparations; Drug Implants; Estrous Cycle; Female; Gonadotropin-Releasing Hormone; Ovary; Ovulation Induction; Progesterone; Pseudopregnancy; Rabbits; Sexual Maturation; Triptorelin Pamoate

Aggression among male animals can be difficult to manage in captive populations, and several strategies including separation, castration, and behavioral modification have been used with varying degrees of success. Many aggression issues are normal sequela from hormonal fluctuations occurring when an animal reaches sexual maturity or during the breeding season, and multi-male groups can be especially problematic as the individuals vie for dominance. In this case, aggression in an all-male group of Rock Hyrax (Procavia capensis) has been managed successfully with serial deslorelin implantation for the past 5 years. Zoo Biol. 35:201-204, 2016. © 2016 Wiley Periodicals, Inc.

Topics: Aggression; Animals; Animals, Zoo; Drug Implants; Enzyme Inhibitors; Hyraxes; Male; Triptorelin Pamoate

Breeding clouded leopards (Neofelis nebulosa) ex situ has been a challenge, primarily due to extreme and often fatal male aggression toward females. This study's aim was to determine the degree to which two possible mechanisms-serotonergic pathways and circulating testosterone levels-affect aggressive behavior. Male clouded leopard behavioral and hormonal data were collected during a series of behavior tests administered before and after treatment with either an anxiety-reducing tricyclic antidepressant (clomipramine) or a GnRH agonist (deslorelin). Results showed that clomipramine treatment decreased "overall activity" (P = 0.054) and increased "lying down" (P = 0.0043) and hiding in a "nest box" (P = 0.0023). Clomipramine treatment also decreased the incidence of "growling" during a mirror image stimulation test, relative to non-test periods (P < 0.0001 pre-drug treatment; P = 0.242 peri-drug treatment), indicating reduced aggression. Suppression of the reproductive axis via deslorelin treatment resulted in significant decreases in circulating androgen (P < 0.0001) and glucocorticoid (P < 0.0001), accompanied by decreased aggressive behaviors, including "swatting" (P = 0.0476), "tail flicking" (P = 0.0409), and "growling" during the behavior reaction tests: mirror image stimulation (P < 0.0001 pre-drug treatment: P = 0.7098 peri-drug treatment) and unfamiliar people test (P < 0.0001 pre-drug treatment: P = 0.2666 peri-drug treatment) relative to non-test periods. Both drug treatments provide evidence that multiple mechanisms modulate aggressive behavior in the male clouded leopard, suggesting that serotonergic modulation coupled with circulating androgens may aid in the formation of successful breeding pairs. Zoo Biol. 35:474-486, 2016. © 2016 Wiley Periodicals, Inc.

Topics: Aggression; Androgens; Animals; Animals, Zoo; Antidepressive Agents, Tricyclic; Clomipramine; Enzyme Inhibitors; Felidae; Female; Gonadotropin-Releasing Hormone; Male; Sexual Behavior, Animal; Triptorelin Pamoate

A total of 13 rabbits were treated with a subcutaneous deslorelin long-term release implant (4.7 mg) to study the effect on ovarian function and histologic features of the uterus. Seven rabbits (group 1) were implanted with a slow-release deslorelin implant before onset of puberty for 273 days as a part of a previous study. After resumption of ovarian function had been confirmed, they were implanted again at the age of 430 days. Six adult rabbits (>177 days old; group 2) were implanted with a slow-release deslorelin implant for 273 days. Ovarian function before, during, and after treatment with the implant was assessed by measuring serum progesterone levels 10 days after a challenge injection of a short-acting GnRH (0.8 μg buserelin intramuscularly) on progesterone levels in peripheral blood. Values more than 4 ng/mL progesterone were considered to verify ovarian function. Animals in group 1 underwent ovariohysterectomy during the second treatment with the implant and the uteri, and ovaries were subjected to histopathologic examination. Endometrial hyperplasia and endometritis were observed in 5 of 7 animals. Nonatretic and atretic follicles at different developmental stages, but no active corpora lutea, were present in the ovaries. Ovariohysterectomy of group 2 animals was performed 2 to 12 months after implant removal. The histopathologic examination of the uterus and ovary of four animals neutered during induced pseudopregnancy showed no signs of uterine disorders. In two animals undergoing ovariohysterectomy 12 months after implant removal, endometritis was present. Their ovaries contained follicles at different developmental stages and corpora albicantia. Reversible suppression of ovarian function can be achieved in female rabbits by the use of GnRH slow-release implants administered before or after puberty. The findings of endometrial hyperplasia and endometritis in seven out of 13 rabbits treated once or twice with the implant may indicate that the development of age-related pathologies of the uterus cannot be prevented by the suppression of ovarian function with a long-acting GnRH implant.

Topics: Animals; Buserelin; Delayed-Action Preparations; Drug Implants; Enzyme Inhibitors; Female; Genitalia, Female; Hysterectomy; Ovariectomy; Ovary; Ovulation; Progesterone; Rabbits; Triptorelin Pamoate

To determine the effect of dopamine agonists in a surgically induced endometriosis model on rats.. In this prospective randomized experimental study, surgical induction of endometriosis was performed by autotransplantation technique on 52 adult female Wistar-Albino rats. Endometriosis formation was confirmed by a second-look laparotomy (n:48) 1 month later. Four study groups were randomly generated according to their treatment regimens: group 1 (leuprolide acetate, n = 12), group 2 (bromocriptine, n = 12), group 3 (cabergoline, n = 12) and group 4 (control, n = 12). Endometriotic implants were excised for histopathological examination after treatment at the setting of laparotomy. The mean surface areas and histopathological glandular tissue (GT) and stromal tissue (ST) scores of endometriotic implants were studied and compared among groups.. After 30 days of treatment, the mean surface area of the endometriotic implants of leuprolide acetate, bromocriptine and cabergoline groups was significantly decreased. The regression of endometriotic foci size in comparison to control was highest in group 1, followed by group 2, then group 3. In the histopathological evaluation both the ST and GT scores of group 1, 2 and 3 were significantly decreased in comparison to controls without a statistically significant difference between the groups.. Dopamine agonists are as effective as GnRH agonists in the regression of experimental endometriotic implants in rats. Further trials are needed to elucidate the pathways affected by dopamine agonists.

Topics: Adult; Animals; Antineoplastic Agents; Bromocriptine; Cabergoline; Disease Models, Animal; Dopamine Agonists; Endometriosis; Endometrium; Ergolines; Female; Gonadotropin-Releasing Hormone; Humans; Laparotomy; Leuprolide; Prospective Studies; Random Allocation; Rats; Rats, Wistar; Triptorelin Pamoate

Surgical castration is done in male pet rabbits for reproduction control, to reduce inter-male aggression and to control hyper-sexuality, territory marking and aggression against humans. Alternatives to surgical castration are requested because of a relatively great anaesthetic risk in rabbits. Long-term application of a GnRH agonist implant results in a fully reversible "hormonal" castration in male dogs, cats, boars and many other species. Therefore, the present study using New Zealand White hybrid and German Giant rabbits aimed to investigate the effects of a 4.7mg deslorelin implant in peripubertal male rabbits (SG; n=10), as a mean of hormonal castration. Blood samples (for testosterone measurements), body weight and testicular volume were taken on days (D) 0, 14 and 90. Surgical castration was performed on D90 for testicular histology. Age-matched animals following the same protocol without implant administration served as adult controls (n=5, CG), animals castrated on D0 served as juvenile controls (n=7, JG). Following treatment, testosterone concentrations were not reduced compared to CG; basal testosterone concentrations were only measured in JG. Spermatogenesis was not affected in SG and not different from CG. Application of a slow release GnRH agonist implant does not induce hormonal castration in male rabbits over a period of 90 days indicating that it is not a suitable alternative to surgical castration in this species.

Topics: Animals; Case-Control Studies; Drug Implants; Enzyme Inhibitors; Gonadotropin-Releasing Hormone; Male; Orchiectomy; Rabbits; Testis; Testosterone; Triptorelin Pamoate

The main aim of the study was to assess whether the longer use of a GnRH-agonist implant (deslorelin 4.7 mg, Suprelorin) in toms would lead to the suppression of spermatogenesis comparable with histologic appearance in juvenile animals as was previously described in dogs. The other aims were to monitor the progression of the testes size decrease and development of azoospermia 5 to 7 months after treatment with a GnRH-agonist implant. In animals, 5, 6, and 7 months after GnRH-agonist implant insertion, variable histological appearance of germinal epithelium was found, when tubules with elongating spermatids, round spermatids, spermatocytes, and spermatogonia as the most developed germinal cells were found in each group of toms. In all male cats, 5, 6, and 7 months after implant insertion, testosterone concentrations and testes size significantly differed between the first and the last visit. All animals, except one tom castrated 5 months after implant insertion, developed complete azoospermia. However, in this tom, all spermatozoa were immotile. Treatment with the subcutaneous GnRH-agonist implant was well tolerated, and no treatment-related adverse effects were noted. These results reported the efficacy of 4.7-mg deslorelin implant (Suprelorin) during its 7 months of use. The complete azoospermia confirms its contraceptive effect. However, the histologic evaluation revealed a great individual variability in the degree of spermatogenic suppression. The question as to whether spermatogenesis in toms can be suppressed in all males to the level of spermatogonia/primary spermatocytes after prolonged exposure to deslorelin has yet to be answered.

Topics: Animals; Azoospermia; Cats; Contraception; Contraceptive Agents, Male; Drug Implants; Gonadotropin-Releasing Hormone; Male; Sperm Motility; Spermatogenesis; Testis; Triptorelin Pamoate

Long-acting GnRH agonists have been used both for canine estrus induction and prevention. The objective of the study was to investigate the use of a deslorelin implant as a long-term and reversible contraceptive in prepubertal bitches with special regard to the time of epiphyseal closure. Thirteen healthy, crossbreed, medium-sized prepubertal female dogs were used in this study. An implant containing 9.4 mg (G1, n = 5) and 4.7 mg (G2, n = 4) deslorelin acetate (Suprelorin) or a placebo (sodium chloride 0.9%; G3, n = 4) was inserted subcutaneously in the interscapular region. Estrus was monitored once daily by physical and sexual behavioral changes. Body development, vaginal cytology, and serum progesterone and estradiol 17β concentration were monitored weekly for the first 5 weeks, and then every 3 weeks throughout the treatment period. Radiographic examinations were performed monthly to determine the epiphyseal closure. Half of the deslorelin-treated bitches (G1: n = 2 and G2: n = 2) came into estrus during the 83-week observation period. All animals in the control group showed estrus between the 39th and 64th weeks of observation. Time to puberty averaged 82.7 ± 8.9 and 61.9 ± 9.7 weeks in the deslorelin-treated (G1 and G2) and the control bitches, respectively (P < 0.02). Both deslorelin implants (9.4 and 4.7 mg) can be used efficiently for the long-term prevention of estrus in prepubertal bitches; however, epiphyseal closure is clearly delayed which was without any clinical effect in the present study.

Topics: Animals; Contraception; Dogs; Drug Implants; Epiphyses; Estradiol; Estrus; Female; Sexual Maturation; Time Factors; Triptorelin Pamoate

Physical urticaria is often challenging to diagnose and manage. We present a case of both cholinergic and cold-induced urticaria and discuss the diagnosis and management strategies of these two important conditions.

Topics: Adolescent; Cholinergic Fibers; Cold Temperature; Diagnosis, Differential; Enzyme Inhibitors; Humans; Male; Triptorelin Pamoate; Urticaria

In postnatal domestic cats, GnRH agonists suppressed fecal concentrations of sexual steroids and delayed puberty. The aim of this study was to describe the gross and microscopic morphometric effects of a single administration of the GnRH agonist, deslorelin acetate, on the gonads of postnatally treated cats. Twenty-seven postnatal male (n = 14) and female (n = 13) kittens were randomly assigned to one of the following treatment groups within the first 24 hours of birth: deslorelin acetate (1.6 mg, subcutaneous; DA, n = 16) or control that remained untreated (CO, n = 11) and spayed or castrated immediately after the onset of puberty. After surgical removal, the gonads were gross and histologically assessed. Sertoli cells also were examined immunohistochemically. Comparisons between the treatments were carried out by the Student t test. Gross gonadal wet weight and volume as well as gonadosomatic index were significantly lower in the DA than those in the CO males; these same parameters were not different in females. Primordial (461.4 + 3.0 vs. 1074.3 + 117.5; P < 0.01), primary (59.1 + 13.5 vs. 165.4 + 24.6; P < 0.01), and secondary (17.5 + 2.6 vs. 31.17 + 8.1; P < 0.05) follicles per mm(2) were decreased in DA than in CO gonads. Epididymal sperm motility and morphology were normal in all but two DA cats that had too few sperm to be evaluated. Germinal epithelial height (μm; 39.68 + 0.92 vs. 72.7 + 1.2; P < 0.01) and most of their cellular components as well as the Sertoli (cm(3); 0.1 + 0.02 vs. 0.24 + 0.05; P < 0.01) cells were diminished in the DA cats. Gonadotropin-releasing hormone agonist endocrine disruption during the neonatal critical reproductive time window may have a potential as a contraceptive agent in domestic felids.

Topics: Animals; Animals, Newborn; Cats; Contraception; Female; Gonadotropin-Releasing Hormone; Male; Organ Size; Ovary; Reproduction; Sertoli Cells; Sexual Maturation; Testis; Triptorelin Pamoate

The present study consists of two distinct parts, experiment 1 and experiment 2. In experiment 1, 13 anestrous queens were treated with a 4.7-mg deslorelin subcutaneous implant to assess its effectiveness in inducing estrus in the domestic cat. Deslorelin is currently used for the reversible suppression of ovarian and testicular activity in dogs and cats and for estrus induction in the bitch. Estrus induction is also reported in the queen but never reported with a targeted study. All the queens showed a positive response to the induction protocol, and estrus was detected within an average of 5.0 ± 2.2 days after the implant placement in 13 out of 13 subjects (100%). Seven of 13 queens exhibited behavioral manifestations of estrus, and the mean number of follicles detected at ultrasound examination was 4.8 ± 1.6 per subject. In experiment 2, three of the queens previously treated with deslorelin for estrus induction were submitted to artificial insemination through endoscopic transcervical catheterization, a new nonsurgical technique for intrauterine sperm deposition. All of them (100%) were pregnant after insemination and they gave birth to healthy litters. The study, as a whole, proves the effectiveness of the 4.7-mg deslorelin subcutaneous implants in inducing estrus in the domestic cat and is, to our knowledge, the first study assessing fertility of the induced estruses. Moreover, it shows the effectiveness of endoscopic transcervical catheterization for artificial insemination in the queen.

Topics: Animals; Breeding; Estrus; Female; Hysteroscopy; Insemination, Artificial; Ovarian Follicle; Pregnancy; Pregnancy Outcome; Triptorelin Pamoate; Ultrasonography

The presence of anovulatory haemorrhagic follicles during the oestrous cycle of mares causes financial impacts, slowing conception and increasing the number of services per pregnancy. Non-steroidal anti-inflammatory drugs (NSAIDs) such as meloxicam and phenylbutazone are used in the treatment of several disorders in mares, and these drugs can impair the formation of prostaglandins (PGs) and consequently interfere with reproductive activity. This study aimed to evaluate the effects of treatment with NSAIDs on the development of pre-ovulatory follicles in mares. In total, 11 mares were studied over three consecutive oestrous cycles, and gynaecological and ultrasound examinations were performed every 12 h. When 32-mm-diameter follicles were detected, 1 mg of deslorelin was administered to induce ovulation. The first cycle was used as a control, and the mares received only a dose of deslorelin. In the subsequent cycles, in addition to receiving the same dose of deslorelin, each mare was treated with NSAIDs. In the second cycle, 4.4 mg/kg of phenylbutazone was administered, and in the third cycle, 0.6 mg/kg of meloxicam was administered once a day until ovulation or the beginning of follicular haemorrhage. All of the mares ovulated between 36 and 48 h after the induction in the control cycle. In the meloxicam cycle, 10 mares (92%) did not ovulate, while in the phenylbutazone cycle, nine mares (83%) did not ovulate. In both treatments, intrafollicular hyperechoic spots indicative of haemorrhagic follicles were observed on ultrasound. Thus, our results suggested that treatment with meloxicam and phenylbutazone at therapeutic doses induced intrafollicular haemorrhage and luteinization of anovulatory follicles.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Estrous Cycle; Female; Follicular Phase; Horses; Luteinization; Male; Meloxicam; Ovarian Follicle; Ovulation; Ovulation Induction; Phenylbutazone; Pregnancy; Thiazines; Thiazoles; Triptorelin Pamoate; Ultrasonography

Two adult, male domestic turkeys were treated with implants of deslorelin acetate, a gonadotropin-releasing hormone agonist, to reduce intermale aggression and aggression directed toward the animal care team at a zoologic institution. The turkeys were manually restrained and either two 4.7-mg or two 9.4-mg implants were placed within the pectoral musculature on 3 occasions over the course of approximately 1.5 years. Plasma testosterone concentrations were measured by radioimmunoassay every 2 weeks for the first month after a new implant placement and then monthly thereafter. Testosterone concentrations remained low and aggressive behavior was decreased for a period of several months after implant placement. At necropsy of both birds, no adverse gross or histologic lesions were noted at the implantation sites in the pectoral musculature or within the gonadal tissue. Deslorelin acetate implants are a treatment modality to consider for mitigation of aggression in male domestic turkeys.

Topics: Aggression; Animals; Antineoplastic Agents, Hormonal; Behavior, Animal; Enzyme Inhibitors; Leuprolide; Testosterone; Triptorelin Pamoate; Turkeys

The study uniquely described the clinical value of transabdominal ultrasonography for monitoring features characterizing the estrous cycle in female cheetahs (Acinonyx jubatus). The reproductive tracts of 21 female, nulliparous, and relatively aged (median: 11 and interquartile range: 9.25-14 years) captive cheetahs resident on two sites in Namibia were assessed by transabdominal ultrasound. Subsequently, the ovarian findings on ultrasound were compared with direct visualization while performing laparoscopic sterilization. A combination of these observations supported by concurrent sampling for vaginal cytology and serum progesterone concentrations defined the estrous status of individual animals. At one site, six cheetahs had been implanted with the GnRH agonist, deslorelin as a contraceptive at least once within the preceding 11 years. On ultrasound, 31 uterine horns and 35 ovaries with discernible structures on 28 (86%) were visualized in the 21 cheetahs. The uterine body was difficult to visualize because of its intrapelvic location. Eleven of 19 uteri (58%) visualized showed endometrial edema suggestive of estrogenization. The uteri of four cheetahs (19%) showed evidence of mild cystic endometrial hyperplasia. Paraovarian cysts were seen on ultrasound (n = 21) and laparoscopy (n = 26) in 16 (76.2%) and 18 (85.7%) cheetahs, respectively. Ovarian volumes obtained from ultrasonographically determined dimensions predicted cyclic activity. Laparoscopy showed that 19 ovaries had discernible follicular structures. In the study population, 10 (47.6%) cheetahs were in proestrus or estrus; none in the luteal phase; and 11 (52.4%) in anestrus. Transabdominal ultrasound, in combination with serum progesterone concentrations and vaginal cytology, was used with acceptable accuracy to assess cyclic ovarian activity in captive cheetahs. A considerable proportion of this aged population showed ovarian activity and the prevalence of paraovarian cysts was notable. A history of prior deslorelin treatment was not associated with either reproductive activity or uterine pathology.

Topics: Acinonyx; Aging; Animals; Enzyme Inhibitors; Female; Laparoscopy; Ovarian Cysts; Ovary; Triptorelin Pamoate; Ultrasonography; Uterus; Vagina

Songbirds are widely used in studies of the neurobiology underlying learning, memory and performance of the sounds used in vocal communication. Development and activity of neurons in many brain sites implicated in those behaviors are closely related to levels of circulating testosterone. Approaches to understand the effects of testosterone in songbirds are presently limited to testosterone implants, which elevate testosterone levels to supraphysiological values, or castration, which eliminates gonadal production of testosterone. Previous studies in mammals indicate that GnRH agonists may be an effective tool to reduce testosterone within that range of extremes and without invasive surgery. To evaluate the effectiveness of the GnRH agonist Deslorelin as a tool to modulate levels of testosterone in songbirds, we recorded the effects of Deslorelin in adult male zebra finches. We recorded songs, body mass and blood testosterone levels pre-treatment, then we gave each bird a small subcutaneous implant of Deslorelin. We measured blood plasma testosterone levels weekly and recorded song behavior and gross morphology of brain, testes and heart at the end of each experiment. Testosterone levels were reduced at the 5mg/kg dose, and the very slight song changes we observed at that dose were like those reported for castrated zebra finches. As expected, there were no changes in the number of cells in androgen-sensitive brain structures. Suppression of testosterone at the 5mg/kg dose was reversible through implant removal. Thus, Deslorelin is a new tool to transiently suppress testosterone levels without the invasiveness and undesirable aftereffects of surgical castration.

Topics: Animals; Finches; Gonadotropin-Releasing Hormone; Humans; Male; Testis; Testosterone; Triptorelin Pamoate

The absence of fertility problems in male dogs after a single treatment with deslorelin acetate (Suprelorin(®)) is well acknowledged. However, reports on the application of deslorelin in the bitch and information concerning fertility after implant treatment are still limited. In this retrospective study, data concerning induced and spontaneous oestruses of 39 bitches from 17 breeds, treated with deslorelin acetate implants (4.7 mg Suprelorin(®), Virbac, France), were retrieved to assess post-treatment fertility (ovulation rate, pregnancy rate and litter size). Animals were grouped according to treatment characteristics: group 1 (Gr1) - females submitted to oestrus induction, showing natural oestruses afterwards (n = 19); group 2 (Gr2) - females re-implanted with 4.7 mg deslorelin acetate to re-induce oestrus, showing subsequent spontaneous post-implant oestruses (n = 7); and group 3 (Gr3) - females submitted to a 4.7 mg deslorelin acetate implant for oestrus suppression, evaluated at subsequent spontaneous post-implant oestruses (n = 13). Comparison of fertility traits between induced and post-treatment spontaneous oestruses in Gr1 and Gr2 (short treatments), or between spontaneous oestruses after long-treatment schedules (Gr 3) revealed a slightly better performance in spontaneous cycles compared with induced cycles: ovulation rate post-treatment was 97.1%, 94.1% and 94.4% and the pregnancy rate post-treatment was 91.2%, 88.9% and 84.6% for groups 1, 2 and 3, respectively. Nevertheless, fertility in induced and post-treatment oestruses was considered normal. Moreover, the individual litter size did not differ within groups between induced and spontaneous cycles. From these findings, we concluded that treatment with 4.7 mg deslorelin implants did not compromise the bitches' fertility in subsequent oestruses.

Topics: Animals; Dogs; Drug Implants; Estrus; Female; Fertility; Gonadotropin-Releasing Hormone; Litter Size; Ovulation; Pregnancy; Pregnancy Rate; Retrospective Studies; Triptorelin Pamoate

Thyroid hormones regulate a variety of physiologic functions including metabolism, growth, and reproductive cycling, and these other hormones can impact the thyroid function via the hypothalamic-pituitary axis. For instance, the gonadotropin-releasing hormone agonist, deslorelin, used in nondomestic carnivores for contraception and behavioral control, down-regulates reproductive hormones through this mechanism and so may impact thyroid function. Due to clinical concerns of hypothyroidism in a bachelor group of adult male Pallas' cats (Otocolobus (Felis) manul) which also had deslorelin implants, serum samples from treated captive (n = 8) individuals, untreated captive (n = 25), and free-ranging (n = 9) individuals were analyzed for thyroid hormone concentrations. Total and free thyroxine (TT4 and FT4), total and free tri-iodothyronine (TT3 and FT3), and thyroid stimulating hormone (TSH) were measured although, due to sample volume limitations, not every hormone could be analyzed for every sample. Of these hormones, only FT4 was found statistically different between the deslorelin-treated and untreated groups. As samples were unevenly distributed across season, true comparison between seasons could not be made. The values reported for the untreated captive and free-ranging group, while representing a small sample size, can serve as a baseline assessment when evaluating the thyroid status of captive Pallas' cats.

Topics: Animals; Animals, Zoo; Enzyme Inhibitors; Felis; Male; Reference Values; Thyroid Hormones; Thyroxine; Triiodothyronine; Triptorelin Pamoate

A 13-yr-old female nulliparous Allen's swamp monkey (Allenopitchecus nigroviridis) presented with intermittent excessive vaginal bleeding, cyclical lethargy, and a history of irregular menstrual cycles. Abdominal ultrasonography revealed a subjectively thickened, irregular endometrium, multiple leiomyomata (uterine fibroids), and bilateral anechoic foci on the ovaries. Treatment was initiated with leuprolide acetate i.m. monthly for 6 mo. Recheck ultrasound at 3 mo showed a decrease in leiomyoma diameter and no evidence of active follicles on the ovaries. Eleven months following completion of treatment, clinical signs recurred and the animal was treated with a deslorelin implant. Since implant placement, no vaginal bleeding has been noted.

Topics: Animals; Antineoplastic Agents, Hormonal; Cercopithecinae; Drug Implants; Endometriosis; Enzyme Inhibitors; Female; Leiomyoma; Leuprolide; Monkey Diseases; Triptorelin Pamoate

A 2-year-old female ovariectomised Norwegian Forest cat with a history of post-spaying urinary incontinence was diagnosed with acquired urinary sphincter mechanism incompetence (USMI) after complete clinical and laboratory examination. Although there is no literature regarding the treatment of post-spaying USMI in cats, deslorelin acetate is successful in the treatment of post-spaying USMI in dogs. Deslorelin acetate implants have been shown previously to be effective for contraception and oestrus suppression in queens, and suppression of reproductive function in tomcats. Therefore, deslorelin acetate implant treatment was chosen for treatment of post-spaying USMI in this queen. Follow-up examinations were performed on days 8, 15 and 30 after deslorelin implant insertion. Urinary continence was restored about 25 days after implantation and maintained for at least 15 months, without treatment-related negative effects. In the present case report, the post-spaying urinary incontinence related to the acquired USMI was successfully treated with a deslorelin acetate implant. In addition, safe implantation was easy in cats and the single injection resulted in long-lasting efficacy. Further studies are needed to confirm the usefulness of deslorelin acetate treatment for post-spaying USMI in queens and to better delineate the duration of efficacy.

Topics: Animals; Cats; Drug Implants; Enzyme Inhibitors; Female; Hysterectomy; Ovariectomy; Triptorelin Pamoate; Urinary Incontinence

Red pandas (Ailurus fulgens) are threatened with extinction owing to habitat loss, exacerbated by their unique ecology and low fecundity. Regional breeding programs manage captive red panda populations. Recommendations not to breed may be made for various reasons, including genetic overrepresentation of certain individuals. No recommendations have been published on the use of contraception for red pandas. This article discusses the use of the GnRH analog deslorelin as a reversible method of contraception in both male and female pandas. The mean time from last contraception to conception was 3 years with a 4.6-mg deslorelin implant. The average dose of GnRH implant received was 1.09 mg/kg (range, 0.88-1.32). Males returned to breeding sooner than females. No reproductive side effects were noted with up to three consecutive annual GnRH implants.

Topics: Ailuridae; Animals; Breeding; Contraception; Endangered Species; Female; Male; Time Factors; Triptorelin Pamoate

A significantly reduced gonadotropin and testosterone secretion is a well-described result of long-term administration of GnRH agonists in the male dog and cat. To date, no data are available about the duration of efficacy and the reversibility of treatment-induced effects after long-term treatment with a 4.7 mg deslorelin implant. Seven healthy male European Shorthair cats (3.2 ± 0.5 kg, 1-6 years) were treated with a 4.7 mg deslorelin implant. Blood samples (testosterone, T), testicular volume, penile spines, and mating behavior were recorded once weekly. Considering T > 0.5 ng/mL as the biological endpoint, mean duration of efficacy was 78.8 ± 12.9 weeks (range: 61.7-100.7 weeks) with T concentrations increasing rapidly after the last T less than 0.1 ng/mL (basal) (P < 0.0001), and pretreatment T concentrations being reached after 3 weeks. Testicular volume rapidly increased after the first increase of T (P < 0.001) with pretreatment testicular volume being reached after 6.9 ± 3.4 weeks (5-11 weeks). "Normal" libido reoccurred 88.7 ± 12.4 weeks after treatment, and "normal" mating behavior was observed even later. Fertile matings occurred 7 to 42 weeks after the last T less than 0.1 ng/mL with a mean of 4.0 ± 0.0 kittens, and 13.6 to 47.6 weeks afterwards testicular histology revealed normal spermatogenesis. The present data confirm that the use of slow-release GnRH-agonist implants containing deslorelin in tomcats represents an effective and safe reversible alternative for long-term contraception; however, as number of animals is low, further fertility trials are recommended.

Topics: Animals; Cats; Contraceptive Agents, Male; Drug Implants; Fertility; Gonadotropin-Releasing Hormone; Male; Penis; Sexual Behavior, Animal; Testis; Triptorelin Pamoate

Endometrial biopsy preceding implantation in in vitro fertilization (IVF) treatment causes a type of injury which facilitates implantation. Pre-treatment hysteroscopic evaluation of uterine cavity also raises the success in IVF. This study investigates whether office hysteroscopy and concurrent endometrial biopsy performed in the luteal phase, on the day of GnRH agonist initiation for long protocol, improves subsequent IVF outcome.. A prospective, nonrandomized, controlled study of 128 normoresponder women was performed: In 70 women (study group), office hysteroscopy and concurrent endometrial biopsy were performed on the day of GnRH agonist initiation preceding ET cycle and in 58 women (control group), GnRH agonist was initiated without any intervention. However, uterine cavity was shown to be normal with hysteroscopy within the previous 6 months in those women. Implantation and pregnancy rates were compared between the groups.. Intrauterine pathologies were observed in 28 % of women in the study group. Implantation rate (38 vs. 25 %; p = 0.04) and pregnancy rate per ET (67 vs. 45 %; p = 0.01) were found to be significantly higher in the study group compared to the control group.. Office hysteroscopy and concurrent endometrial biopsy performed in the luteal phase, on the day of GnRH agonist initiation for long protocol, provide direct evaluation of the uterine cavity immediately before ET cycle and also significantly improve the implantation and IVF outcome.

Topics: Adult; Biopsy; Case-Control Studies; Embryo Implantation; Endometrium; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Hysteroscopy; Luteal Phase; Pregnancy; Pregnancy Rate; Prospective Studies; Triptorelin Pamoate; Uterus

Assisted reproductive techniques, such as ovarian manipulation and artificial insemination, are useful for enhancing genetic management of threatened wildlife maintained ex situ. In this study, we used noninvasive fecal hormone monitoring to investigate (1) the influence of pairing with a male on endocrine responses of female maned wolves (Chrysocyon brachyurus) to a GnRH agonist (deslorelin) and (2) the efficiency of recombinant LH (reLH) on ovulation induction in females housed alone. Deslorelin (2.1 mg Ovuplant) was given to females that were either paired with a male (n = 4) or housed alone (n = 7); the implant was removed 7 to 11 days postimplantation. Three of seven singleton females were injected with reLH (0.0375 mg) on the day of implant removal, whereas the remaining females (n = 4) did not receive the additional treatment. Fecal samples were collected 5 to 7 days/wk from all females starting 11 days prior to hormone insertion until at least 70 days post implant removal for a total of 11 hormone treatment cycles. Fecal estrogen and progestagen metabolites were extracted and analyzed by enzyme immunoassay. Evidence of ovulation, demonstrated by a surge of estrogen followed by a significant rise in progestagen, occurred in all paired females. Three of the four singleton females that did not receive reLH treatment exhibited no rise in progestagen after an estrogen surge. All singleton females treated with reLH exhibited a rise in fecal progestagen after injection, indicating ovulation. In conclusion, deslorelin is effective at inducing ovarian activity and ovulation in paired female maned wolves; however, exogenous reLH is needed to induce ovulation in females housed alone. The findings obtained from this study serve as a foundation for future application of artificial insemination to enhance genetic management of this threatened species ex situ.

Topics: Animals; Canidae; Conservation of Natural Resources; Endangered Species; Female; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Ovulation Induction; Triptorelin Pamoate

Reproduction control of small mammals is challenging. The purposes are the control of fertility and the reduction of sexual behaviour, aggressiveness and odour. Moreover, some species like ferret females need to be neutered to prevent bone marrow suppression caused by hyperoestrogenism. Many methods of sterilization have been reported, including surgical and chemical techniques. This article describes the reproductive physiology of ferrets and the techniques used to control their reproduction. Some aspects of the use of long-acting deslorelin implants in rabbits and rodents are also described.

Topics: Animals; Contraceptive Agents, Female; Contraceptive Agents, Male; Drug Implants; Female; Ferrets; Male; Orchiectomy; Ovariectomy; Rabbits; Rodentia; Triptorelin Pamoate

Contraception is necessary to manage zoo animal populations and to be able to house animals in groups without producing additional unwanted offspring. In felids and canids, an association between exposure to progestins and the occurrence of endometrial and mammary gland pathology has been documented. Therefore, the Association of Zoos and Aquariums (AZA) Wildlife Contraceptive Center recommends the use of deslorelin acetate for long-term contraception in carnivores. Return to cyclicity after deslorelin treatment has been variable; some individuals show ovarian suppression for long periods after the expected end of the deslorelin efficacy. In an attempt to reduce the time to reversal, techniques to locate and remove previous implants are being developed. This report documents the successful implementation of high-frequency ultrasonography in lions (Panthera leo) to locate and direct surgical removal of multiple deslorelin implants placed at least 2 yr previously as well as the return of follicular activity in both females at 7 months post-removal of implants.

Topics: Animals; Animals, Zoo; Contraceptive Agents, Female; Drug Implants; Enzyme Inhibitors; Female; Lions; Triptorelin Pamoate

Slow-release GnRH agonist implants are considered an effective, reversible alternative to surgical castration in male tom cats. Individual differences exist regarding the onset of efficacy and might be delayed in some animals. Single measurements of testosterone (T) might result in basal concentrations also in intact male cats. Consequently, GnRH stimulation tests are performed to measure T increase in intact animals and to differentiate castrated from intact male cats. In this study, five tom cats were treated with a 4.7-mg deslorelin implant and GnRH stimulation tests using buserelin were performed before treatment and at 4-week intervals afterward until Week 20. After the last test in Week 20 all animals were castrated. Four of five animals had basal T after 4 weeks and-in contrast to pretreatment-application of buserelin did not result in any further T increase. In one animal, T was low after implant insertion, but not basal; however, a GnRH stimulation test induced a slight increase of T in Week 8 and 16 only and no response in Weeks 4, 12, and 20. Testicular volume was significantly decreased and penile spines disappeared in all cats. Testicular histology showed mixed atrophy, but also fully elongated spermatids in three of five male cats making infertility questionable. Because of the loss of the stimulatory effect of short-term GnRH application (buserelin), it can be assumed that long-term GnRH agonists also act by some mechanisms of downregulation of pituitary GnRH receptors in the tom cat.

Topics: Animals; Buserelin; Castration; Cats; Contraception; Down-Regulation; Drug Implants; Gonadotropin-Releasing Hormone; Male; Pituitary Gland; Receptors, LHRH; Testosterone; Triptorelin Pamoate

To compare the serum and follicular fluid (FF) concentrations of stem cell factor (SCF) as well as the serum urocortin 1 (UCN1) concentration in gonadotropin-releasing hormone antagonist (GnRH-ant) and gonadotropin-releasing hormone agonist (GnRH-a) protocols for controlled ovarian hyperstimulation (COH) in IVF patients.. Follicular fluids and blood samples of 42 infertile women undergoing COH for IVF-embryo transfer with either GnRH agonist (n = 22) or GnRH antagonist (n = 20) protocols from 2010 to 2011 were collected during oocyte retrieval. SCF concentrations of serum and FF were assessed by sandwich enzyme immunoassay using ELISA Kit for SCF kid. Serum UCN1 concentration were measured using commercially available enzyme-linked immunosorbent assay.. Concentrations of serum UCN1, serum and FF SCF were similar in the two groups. The serum SCF levels correlated strongly with the follicular SCF levels (r = 0.770, p < 0.001). The mean implantation rate, biochemical and clinical pregnancy rate and live birth rate per cycle were also similar in the groups.. These observations suggest that there is no significant difference in follicular microenvironment in terms of SCF and UCN1 between agonist and antagonist protocols.

Topics: Adult; Embryo Implantation; Embryo Transfer; Enzyme-Linked Immunosorbent Assay; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Follicular Fluid; Gonadotropin-Releasing Hormone; Gonadotropins; Hormone Antagonists; Hormones; Humans; Infertility, Female; Oocyte Retrieval; Ovarian Hyperstimulation Syndrome; Ovary; Ovulation Induction; Pregnancy; Pregnancy Rate; Stem Cell Factor; Triptorelin Pamoate; Urocortins

Gonadotropin-releasing hormone (GnRH) agonists are routinely used to suppress the reproductive axis of many mammals, especially in zoos. Current treatments are reversible. There is a need to develop nonreversible agents, and this study investigates the effects of high-dose and long-duration exposure to the GnRH agonist, deslorelin, in the rat model. Studies indicate that the follicle-stimulating hormone (FSH) gonadotropin is predominantly affected, and following high-dose exposure to deslorelin for a long duration, the ability of gonadotropes to synthesize FSH may be compromised, perhaps permanently. Understanding the mechanisms by which such persistent suppression of FSH occurs may facilitate the development of novel next-generation contraceptives. It is hypothesized that direct testicular effects of GnRH agonists may play a critical role in the efficacy of GnRH agonists in male contraception.

Topics: Animals; Contraceptive Agents, Male; Dose-Response Relationship, Drug; Drug Implants; Enzyme Inhibitors; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Male; Rats; Testis; Triptorelin Pamoate

The objective of the present study was to investigate the inhibitory effects of long-term deslorelin implant administration on the ovarian and uterine structures of female rats. A total of 16 non-pregnant female rats were randomly assigned to two groups, each consisting of eight animals. Animals in the implant group (DESL) received subcutaneously (s.c.) a single deslorelin implant (4.7 mg), an analogue of GnRH, while no treatment was applied to the control group (CON). A single adult male rat was introduced into the cages of both the DESL and CON females after 6 weeks of implant administration. After 1 year of implant administration, all animals were killed and follicular structures and volumes of ovaries and uterus were examined using stereological methods. Stereological observations showed that the mean ovarian total volume of the DESL group (0.28 ± 0.07 cm(3)) was lower than that of the CON group (1.55 ± 0.23 cm(3)) (p < 0.001). On the other hand, the total number of pre-antral follicles in the ovaries of DESL (555.32 ± 151.47) females were significantly lower than the control group (1162.96 ± 189.19) (p < 0.001). In the DESL group, the mean volumes of epithelium, endometrium, myometrium and total volume of the uterus were significantly (p < 0.001) lower than in the control groups. In conclusion, these findings indicate that the long-term deslorelin implant (i) interferes with the normal cyclicity of female rats and (ii) affects the pre-antral follicle population. Further studies will be required to determine the effects of long-term deslorelin treatment on the pre-antral follicle numbers and future fertility in other species.

Topics: Animals; Drug Implants; Enzyme Inhibitors; Female; Gonadotropin-Releasing Hormone; Male; Ovarian Follicle; Pregnancy; Rats; Rats, Wistar; Triptorelin Pamoate; Uterus

Suppression of oestrus is of major interest in feral cat populations, but also in breeding queens temporarily not intended for breeding. Slow release gonadotropin-releasing hormone (GnRH) agonist implants are a new off-label approach for reproduction control in cats. However, initially, oestrus induction may occur and no data exist regarding what happens if previously mated queens are treated. This case report presents a queen mismated 9 and 8 days before treatment with a 4.7 mg deslorelin implant. The queen delivered four healthy kittens 66 days after mismating, but showed no interest in the kittens and lactation was not adequate. Progesterone and oestradiol concentrations were monitored and the queen was followed until the return of oestrus and subsequent breeding. The next oestrus was observed 498 days after treatment and the queen was mated in the second oestrus afterwards, became pregnant and delivered two healthy kittens, both of which were raised successfully by the queen. This case report clearly shows that pregnancy following a GnRH-agonist implant may go to term, but maternal care might be influenced owing to hormonal changes induced by treatment. In addition, this is the first report demonstrating reversibility of effects induced by long-term treatment with a deslorelin implant (return to oestrus, fertility and normal maternal care).

Topics: Animals; Cats; Contraception; Contraceptive Agents, Female; Drug Implants; Enzyme Inhibitors; Female; Gonadotropin-Releasing Hormone; Ovarian Follicle; Pregnancy; Pregnancy, Animal; Sexual Behavior, Animal; Triptorelin Pamoate

GNRH significantly inhibits proliferation of a proportion of cancer cell lines by activating GNRH receptor (GNRHR)-G protein signaling. Therefore, manipulation of GNRHR signaling may have an under-utilized role in treating certain breast and ovarian cancers. However, the precise signaling pathways necessary for the effect and the features of cellular responses remain poorly defined. We used transcriptomic and proteomic profiling approaches to characterize the effects of GNRHR activation in sensitive cells (HEK293-GNRHR, SCL60) in vitro and in vivo, compared to unresponsive HEK293. Analyses of gene expression demonstrated a dynamic response to the GNRH superagonist Triptorelin. Early and mid-phase changes (0.5-1.0 h) comprised mainly transcription factors. Later changes (8-24 h) included a GNRH target gene, CGA, and up- or downregulation of transcripts encoding signaling and cell division machinery. Pathway analysis identified altered MAPK and cell cycle pathways, consistent with occurrence of G(2)/M arrest and apoptosis. Nuclear factor kappa B (NF-κB) pathway gene transcripts were differentially expressed between control and Triptorelin-treated SCL60 cultures. Reverse-phase protein and phospho-proteomic array analyses profiled responses in cultured cells and SCL60 xenografts in vivo during Triptorelin anti-proliferation. Increased phosphorylated NF-κB (p65) occurred in SCL60 in vitro, and p-NF-κB and IκBε were higher in treated xenografts than controls after 4 days Triptorelin. NF-κB inhibition enhanced the anti-proliferative effect of Triptorelin in SCL60 cultures. This study reveals details of pathways interacting with intense GNRHR signaling, identifies potential anti-proliferative target genes, and implicates the NF-κB survival pathway as a node for enhancing GNRH agonist-induced anti-proliferation.

Topics: Animals; Antineoplastic Agents, Hormonal; Apoptosis; Biomarkers; Blotting, Western; Cell Cycle; Cell Differentiation; Cell Proliferation; Enzyme Inhibitors; Female; Flow Cytometry; Gene Expression Profiling; Humans; Immunoenzyme Techniques; Kidney; Mice; Mice, Nude; NF-kappa B; Oligonucleotide Array Sequence Analysis; Phosphoproteins; Protein Array Analysis; Proteomics; Rats; Real-Time Polymerase Chain Reaction; Receptors, LHRH; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Signal Transduction; Triptorelin Pamoate

Although slow release GnRH-agonist implants have been shown to effectively suppress the estrous cycle in queens, there are still several remaining questions about their use: if the probability and frequency of estrus induction because of initial stimulation is dependent on the stage of cycle when animals are treated, if all effects are reversible, and to what extent fertility is regained after the end of efficacy. The latter is of major interest to cat breeders who want temporary suppression of estrus in breeding animals. Twenty queens (14 with known fertility) were treated with a 4.7 mg deslorelin implant; hormonal changes (progesterone [P4], and estradiol [E2]) and behavioral changes with special respect to estrus signs and subsequent fertility were assessed. Group A cats (N = 10) were treated 3.2 ± 0.8 days after the beginning of estrus and estrus stopped 4.1 ± 2.5 days after treatment. Estrus induction was observed in one queen 6 days after treatment, and one queen showed estrous signs 138 and 155 days after treatment. Progesterone increased significantly after treatment in all animals until day 14, then slowly decreased reaching basal levels on day 56 without any further increase. Group B cats (N = 10) were treated 7 days after the end of estrus; nine cats had P4 > 1.5 ng/mL and basal E2, one cat (B10) had basal E2 and P4. In cat B10 estrus induction occurred after treatment, but in none of the others; however, E2 increased in all group B cats 1 day after treatment but reached pretreatment concentrations on Day 7 again and remained basal. The implant was still effective in one animal of the estrus group with a duration of efficacy >1102 days, in the others duration of efficacy varied between 483 and 1025 days. Eight queens were mated afterwards and gave birth to a healthy litter with 3.3 ± 1.5 kittens. This study proves that (1) the incidence of estrus induction-although very low-is highest after treatment in estrus or postestrus, (2) the duration of efficacy varies between 16 and 37 months, and (3) estrus suppression is reversible and animals remain fertile after the treatment effect has expired.

Topics: Animals; Cats; Contraception; Contraceptive Agents, Female; Drug Implants; Estradiol; Estrus; Female; Fertility; Gonadotropin-Releasing Hormone; Pregnancy; Progesterone; Triptorelin Pamoate

The aim was to elucidate the role of LH and FSH in testicular development and growth in the neonatal boar. On Day 10 after birth (Day 0 of study), animals were assigned to one of nine groups (n=6): Group 1, control, no treatment; Group 2, hemicastrated (H); Group 3, H and implanted with GnRH agonist (H+GnRH); Group 4, H+GnRH+FSH 200μg/kg daily from Days 0 to 14 (D0-14); Group 5, H+GnRH+FSH 400μg/kg D0-14; Group 6, H+GnRH+FSH 400μg/kg in PVP D0-14; Group 7, H+GnRH+LH 200μg/kg D0-14; Group 8, H+GnRH+LH 400μg/kg D0-14; Group 9, H+GnRH+LH and FSH 200μg/kg D0-14. The right testis in control and hemicastrated boars was removed on Day 15. Hemicastrated boars had greater (P<0.05) testicular growth than control boars and testicular growth was prevented in boars treated with GnRH agonist. FSH induced Sertoli cell proliferation but not testicular growth whilst LH induced Leydig cell proliferation and testicular growth was similar to control boars but less than hemicastrated boars. LH+FSH induced similar testicular growth as LH alone and neither LH and/or FSH supported testicular hypertrophy in hemicastrated boars. The findings show conclusively for the first time that LH and FSH respectively induce Leydig cell and Sertoli cell proliferation in the neonatal boar. LH additionally supports a normal increase in testicular size in the neonatal boar.

Topics: Animals; Follicle Stimulating Hormone; Luteinizing Hormone; Male; Organ Size; Random Allocation; Swine; Testis; Testosterone; Triptorelin Pamoate

In six German Shepherds dogs, GnRH agonist implants (Deslorelin) were inserted subcutaneously one month after histological confirmation of benign prostatic hyperplasia (BPH). Prostatic volume (PV), characteristics of ejaculate, serum testosterone concentrations and Doppler parameters of prostatic and subcapsular arteries were detected at different time intervals, for 6 month. The prostatic volume showed a significantly reduction starting at day 37. The decrease in sperm concentration, motility and increase in morphological abnormal sperm were observed from day 22 to day 37, when it was no longer possible to obtain the ejaculate. The values of peak systolic velocity and end-diastolic velocity in prostatic and subcapsular arteries showed from day 11 a gradual decrease, significant at day 22 until day 37 and reaching the lowest values at day 52 until the end of observation. The power Doppler pixel intensity of both arteries showed a gradual decrease from day 5 until day 52. In particular, a significant decrease was observed for both arteries from day 11. Testosterone serum concentration decreased to undetectable levels by day 11 until the end of the observations. All these Doppler parameters and testosterone values were positively correlated with the prostatic volume. Furthermore, testosterone values were positively correlated with peak systolic velocity, end diastolic velocity and pixel numbers. The use of implants containing GnRH analogues, even in asymptomatic subjects, is effective for the control of BPH and the application of Doppler exam of prostatic blood flow represent an non-invasive tool for monitoring the response of medical treatment.

Topics: Animals; Arteries; Blood Flow Velocity; Dog Diseases; Dogs; Drug Implants; Gonadotropin-Releasing Hormone; Male; Prostate; Prostatic Hyperplasia; Semen Analysis; Testosterone; Triptorelin Pamoate; Ultrasonography, Doppler

The aim of the present study was to investigate the safety and efficacy of deslorelin, a GnRH agonist, implants in suppressing estrus behavior and matings in a controlled ambient environment in feline queens in the presence of a tomcat. Local and utero-ovarian side effects of deslorelin implants were also investigated. The queens were housed in groups and assigned to one of three treatments: group 1 received 9.5 mg deslorelin implants (N = 14), group 2 received 5 mg megestrol acetate tablets and 9.5 mg deslorelin implants (N = 7), and group 3 were given placebo implants (N = 7). All implants were placed subcutaneously cranial to the interscapular region under xylazine hydrochloride sedation. Ovarian activity was monitored by fecal estradiol (E(2)) analyses. The animals were observed daily and checked individually at three-day intervals for behavioral signs of estrus. After 18.5 mo of trial, queens were ovariohysterectomized, and ovaries and uteri were weighed and evaluated histologically. E(2) levels were significantly lower in group 1 and 2 than in group 3 with an average of 128.48 ± 19.97 ng/g, 90.44 ± 7.16 ng/g and 283.26 ± 39.21 ng/g, respectively, excepting the first week of treatment. After inserting implants an initial estrus-like increase in fecal E(2) concentrations occurred in all treated queens except one female in group 2. Ovarian and uterine weights were significantly different among the groups (P < 0.01), and were lowest in groups 1 and 2. Primordial and primary follicle numbers were significantly higher in groups 1 and 2 than in group 3 (P < 0.001). Endometrial gland, antral follicle, and corpus luteum (CL) numbers were highest in group 3 (P < 0.01, 0.001, and 0.001, respectively) compared with groups 1 and 2. Deslorelin implants successfully suppressed estrus behavior and E(2) secretion in queens for 18.5 mo of the study period. Further investigations are needed to demonstrate the effects of GnRH agonists on ovarian interstitial tissue.

Topics: Absorbable Implants; Animals; Cats; Contraceptive Agents, Female; Estradiol; Estrus; Feces; Female; Ovary; Pregnancy; Triptorelin Pamoate; Uterus

Effective contraception would enhance genetic management of captive Pteropus species, which typically breed well in captivity. Male reproductive seasonality was monitored (15-mo interval) in captive P. alecto (6 controls and 5 treated with 4.7 mg deslorelin). In untreated males, there were seasonal changes in testicular volume, body weight and testosterone secretion; testicular volume and body weight peaked in February and March, respectively, whereas testosterone concentration remained >5 ng/ml before rising (P < 0.001) to 24.9 ± 3.6 ng/ml (mean ± SEM) in April. However, there was no corresponding change in sperm quality, and seminal vesicle gland (SVG) secretions remained present in ejaculates. In treated males, testosterone concentration had an initial 'flare' response (mean ± SEM peak: 19.95 ± 3.27 ng/ml) before declining (P < 0.001) by 32 d to basal levels, where it remained. In these males, there was reduced sperm motility after 1 mo (P < 0.001) and the absence of SVG secretions after 4 mo. However, aspermic ejaculates were first recorded 5 mo post-treatment. At 10 mo after treatment, spermatogenesis was still disrupted, when membrane-intact, but non-motile sperm were present in two individuals. Motile sperm were first recovered from one of these males 13 mo after deslorelin treatment. We concluded that captive P. alecto males: (a) had seasonal reproductive changes in testicular volume, body weight and testosterone secretion; (b) produced motile, membrane-intact sperm and SVG secretions throughout the year; and (c) had a rapid decline in testosterone concentration and consequent suppression of testicular function for at least 5 mo following deslorelin administration.

Topics: Animals; Chiroptera; Contraceptive Agents, Male; Enzyme Inhibitors; Gonadotropin-Releasing Hormone; Male; Seasons; Sexual Behavior, Animal; Triptorelin Pamoate

Gonadotrophin-releasing hormone (GnRH) agonists are used to treat gonadal steroid-dependent disorders in humans and to contracept animals. These agonists are considered to work by desensitising gonadotrophs to GnRH, thereby suppressing follicle-stimulating hormone (FSH) and luteinising hormone (LH) secretion. It is not known whether changes occur in the cellular composition of the pituitary gland after chronic GnRH agonist exposure. Adult male Sprague-Dawley rats were treated with a sham, deslorelin, or deslorelin plus testosterone implant for 41.0 ± 0.6 days. In a second experiment, rats were castrated and treated with deslorelin and/or testosterone. Pituitary sections were labelled immunocytochemically for FSHβ and LHβ, or gonadotrophin α subunit (αGSU). Deslorelin suppressed testis weight by two-thirds and reduced plasma FSH and LH in intact rats. Deslorelin decreased the percentage of gonadotrophs, although the effect was specific to the FSHβ-immunoreactive (-ir) cells. Testosterone did not reverse the deslorelin-induced reduction in the overall gonadotroph population. However, in the presence of testosterone, the proportion of gonadotrophs that was FSHβ-ir increased in the remaining gonadotrophs. There was no effect of treatment on the total LHβ-ir cell population, although the loss of FSHβ in bi-hormonal cells increased the proportion of mono-hormonal LHβ-ir gonadotrophs. The castration-induced plasma LH and FSH increases were suppressed by deslorelin, testosterone or both. Castration increased both LH-ir and FSH-ir without increasing the overall gonadotroph population, thus increasing the proportion of bi-hormonal cells. Deslorelin suppressed these increases. Testosterone increased FSH-ir in deslorelin-treated castrate rats. Deslorelin did not affect αGSU immunoreactivity, suggesting that the gonadotroph population per se is not eliminated by deslorelin, although the ability of gonadotrophs to synthesise FSHβ is compromised. We hypothesise that the FSH dominant suppression may be central to the long-term contraceptive efficacy of deslorelin in the male.

Topics: Animals; Down-Regulation; Follicle Stimulating Hormone; Gonadotrophs; Gonadotropin-Releasing Hormone; Hormone Antagonists; Immunohistochemistry; Male; Orchiectomy; Organ Size; Pituitary Gland; Rats; Rats, Sprague-Dawley; Testis; Time Factors; Triptorelin Pamoate

Deslorelin acetate implants, recently licensed in Ireland and the UK for ovulation induction in mares, have been associated with prolonged interovulatory intervals in USA studies, leading to the practice of removing implants postovulation. Trial data in Australia indicate a less pronounced effect on interovulatory intervals, suggesting possible geographical variation. Objectives of the current study were to assess the effect of deslorelin implants, with and without removal on oestrous cycle length in Irish- and UK-based Thoroughbred broodmares. Data were collected retrospectively from 88 oestrous cycles. A statistically significant difference (P=0.02) was found between interovulatory intervals in mares in which the deslorelin implant was not removed, compared with administration and removal of the implant or the use of human chorionic gonadotrophin. The results suggest that implant removal when possible is advisable. The delay in subsequent ovulations was less marked than that reported in some studies from the USA. This information is useful in deciding when to schedule subsequent breeding for mares which received a deslorelin implant during the previous oestrous period and provides evidence to counter-concerns that mares treated with deslorelin implants may experience a long delay in return to oestrus if the implant is not removed.

Topics: Animals; Drug Implants; Enzyme Inhibitors; Estrus; Female; Horses; Ireland; Ovulation; Ovulation Induction; Time Factors; Triptorelin Pamoate

Topics: Animals; Enzyme Inhibitors; Female; Horses; Ovulation; Ovulation Induction; Triptorelin Pamoate

The estrous cycle length in the white rhinoceros (Ceratotherium simum) is either 4 or 10 wk. The cause(s) for this variation as well as the poor fertility rate in captivity remains under debate in this species. Most captive adult white rhinoceros undergo long anovulatory periods without luteal activity which are considered a major reason for their low reproductive rate. In this study, the synthetic progestin chlormadinone acetate (CMA) was tested in combination with hCG or the GnRH analogue deslorelin for its efficiency to induce ovulation in fourteen females without luteal activity and in three, regular cycling females. HCG (N = 12), injectable GnRH analogue (N = 8) and GnRH analogue implants (N = 15) were given to induce ovulation after CMA treatment. Treatment success was determined using both transrectal ultrasonography and progesterone metabolite EIA analysis. A preovulatory sized follicle (3.5 ± 0.1 cm) or a corpus luteum (5.1 ± 0.7) was present on the ovary one day after induction in 93.1% of the treatments. Despite this high rate of ovarian response, ovulation rate differed between the study groups. The ovulation rate for hCG, injectable GnRH analogue and GnRH analogue implants was 66.7%, 62.5% and 93.3%, respectively. Ovulation rate in cyclic females treated with GnRH implants was 100% (6/6) compared with 89% (8/9) in females without luteal activity receiving the same treatment. The length of the estrous cycle when induced with hCG was 4 wk (85.7%). The estrous cycle when induced with GnRH analogue was predominantly 10 wk long. Two females without luteal activity treated with GnRH became pregnant. In conclusion, CMA in combination with GnRH analogue implants was highly effective to induce ovulation in white rhinoceroses and thus can contribute to efforts aimed at increasing natural mating and reproductive rates in the captive white rhinoceros population.

Topics: Animals; Breeding; Chlormadinone Acetate; Chorionic Gonadotropin; Drug Implants; Estrous Cycle; Estrus; Estrus Synchronization; Female; Ovarian Follicle; Ovulation Induction; Perissodactyla; Pregnancy; Reproduction; Treatment Outcome; Triptorelin Pamoate; Ultrasonography

The jill is a long-day breeder with a constant oestrus without mating. Persistent oestrogen production results in clinical signs of hyperoestrogenism including pancytopenia and death if untreated. As spaying is thought to be related to the development of hyperadrenocorticism, a non-invasive, safe and effective long-term treatment is needed for oestrus suppression in jills. Seven jills in oestrus were treated with a 4.7mg deslorelin implant. Blood samples for estradiol-17ß (E2) and progesterone (P4) determination were obtained before as well as 4 and 8 weeks after treatment; data are given as geometric mean (deviation factor, DF). Mean E2 was 280.2 pmol/L (1.7) before, 36.4 pmol/L (1.4) 4 and 21.6 pmol/L (1.1) 8 weeks after treatment (p < 0.0001). P4 before treatment was 1.4 nmol/L (2.6), 57.8 nmol/L (1.9) on week 4 and 3.8 nmol/L (2.6) on week 8 (p < 0.0001) indicating ovulation had occurred after implant insertion. Oestrous signs within the observation period of up to 32 months remained suppressed.

Topics: Animals; Drug Implants; Estrogens; Estrus; Female; Ferrets; Gonadotropin-Releasing Hormone; Triptorelin Pamoate

North American zoos began using melengestrol acetate (MGA) implants to control reproduction in wild felids in the mid-1970s. Research linking MGA and other progestin-based contraceptives to uterine and mammary pathology in canids as well as felids resulted in a shift to GnRH agonist implants (Suprelorin(®): deslorelin, Peptech Animal Health, Australia). However, a recent study revealed an association between Suprelorin(®) and uterine pathology in canids, but that pathology was not found in canids treated with oral megestrol acetate (MA) for 2 weeks around the time of implant insertion to prevent the initial agonist stimulation phase. Thus, the AZA Wildlife Contraception Center (WCC) currently recommends Suprelorin(®) plus the 2-week MA regimen for wild canids and felids. WCC research is now focusing on factors affecting Suprelorin(®) reversibility.

Topics: Animals; Animals, Wild; Animals, Zoo; Canidae; Contraceptive Agents; Drug Implants; Endangered Species; Felidae; Female; Megestrol Acetate; Practice Guidelines as Topic; Triptorelin Pamoate

Over the last 10-15 years, long-acting GnRH agonists have become widely available. In the field of small animal reproduction, most recent studies have focused on the use of two compounds developed under the form of subcutaneous implants: azagly-nafarelin and deslorelin. Only the latter has been commercially available for use in male dogs, first in Australia and New Zealand, then in several countries of the European Union since 2008. Although officially marketed for male dogs, this compound has also been studied in bitches and more recently in queens. Some published papers or recent presentations at congresses--still unpublished--have focused on the use of GnRH agonists implants in females.

Topics: Animals; Cats; Contraception; Contraceptive Agents; Dogs; Drug Implants; Estrus; Female; Gonadotropin-Releasing Hormone; Triptorelin Pamoate

Stray dogs are a significant problem in large cities. Contraception is an important and useful solution to control the growing population of these dogs. Early-age neutering is an effective technique for canine population control; however, surgical neutering may not be possible in various situations. GnRH-agonist implantation has been successful for long-term reversible contraception in dogs. The efficacy of GnRH-agonist implantation on long-term suppression of reproductive performance was observed in male dogs. Eleven 4-month-old dogs were implanted with 4.7, 9.4 mg deslorelin or placebo. Sexual behaviour and testicular size were monitored every 2 months. Ejaculates were collected and evaluated at 8, 12, 15, 18, 24, 30, 32, 34 and 36 months of age. Dogs implanted with placebo were found to be healthy and in normal reproductive status. Most dogs (3/4) implanted with 4.7 mg deslorelin showed male sexual behaviour at age of 34 months old. From this group, two dogs had normal semen quality, while semen could not be collected from the other dog, and after castration, no sperm were obtained following epididymal flushing. One dog implanted 4.7 mg deslorelin and four dogs implanted with 9.4 mg deslorelin remained in the non-pubertal reproductive status at 30-34 months. The delay to puberty was longer in dogs implanted with higher dose of GnRH agonist. Implantation of pre-pubertal dogs with high doses of GnRH agonist will delay the onset of puberty and may be an effective strategy to reduce the number of unwanted breedings.

Topics: Animals; Contraception; Contraceptive Agents, Male; Dogs; Gonadotropin-Releasing Hormone; Male; Reproduction; Sexual Maturation; Testis; Triptorelin Pamoate

The aim of the present study was to test for the efficacy of a slow release GnRH-agonist implant (4.7 mg deslorelin, Suprelorin) in the male cat. Ten toms were implanted sc in the neck. Changes in testosterone (T) secretion, testicular size, body weight and behaviour (mounting, mating, urine marking) were monitored. T concentrations were significantly decreased (P < 0.0001) to basal levels (< 0.1 ng/mL) in 5 of 10 cats after 4 weeks and in all but one tom after 11 weeks (T < 0.1 ng/mL). In this respective tom only partial downregulation with T-values from 0.2 to 0.1 ng/mL was achieved until week 27. In weeks 28 and 32, T concentrations were below 0.1 ng/mL. Compared to pretreatment values, testicular volume was significantly decreased by about 60% in week 12 and about 73% after 36 weeks (P < 0.001). Penile spines disappeared 9.4 ± 1.0 weeks after treatment. Food intake was significantly increased during treatment period (P < 0.001). In all tomcats libido, mating behaviour and urine marking were significantly reduced (P < 0.0001) after an initial stimulation. In one tom, mating an oestrous queen on day 20 after implant administration resulted in pregnancy. Mating of another tom that had T-values between 0.1 and < 0.1 ng/mL since day 24 in week 8 revealed the presence of spermatozoa; however, this mating did not result in pregnancy. Subcutaneous implant administration was well tolerated by all tomcats without sedation or anaesthesia and no treatment related negative effects were observed. These results demonstrate the clinical efficacy of the 4.7 mg deslorelin implants (Suprelorin) in the tom inducing all castration related effects.

Topics: Animals; Body Weight; Cats; Contraception; Drug Implants; Eating; Gonadotropin-Releasing Hormone; Male; Orchiectomy; Reproduction; Sexual Behavior, Animal; Testis; Testosterone; Triptorelin Pamoate

Estrogens, gonadotrophins, dopamine agonists, gonadotrophin releasing hormone (GnRH) and its agonists have been used for estrus induction in bitches. A long acting GnRH agonist implant (4.7 mg Deslorelin; Suprelorin®, Virbac) with a continuous hormone release has been developed for suppression of sexual function in male dogs. In this study we administered the Deslorelin implant placed subcutaneously on the medial side of the leg to induce estrus in 11 anestrous Beagle bitches (group A). 6 Beagle bitches (group B) with a spontaneous estrous cycle were used as controls. The progress of pre-estrus and estrus was documented by behaviour, vaginoscopy, vaginal cytology and progesterone concentration. In group A a bloody vaginal discharge was detected on average 4.8 (range 3-10) d after application of the implant. At this moment implants were removed under local anaesthesia. Pre-estrus lasted for an average of 4.5 d (range 1-12). All bitches showed estrous signs and ovulated. The ovulation took place on day 8.2 (range 4-15) after start of pre-estrus. In group B pre-estrus lasted for 7.5 d (range 6-9), and the mean day of ovulation was day 11 (range 9-13). As a consequence of ovulation, progesterone serum concentrations exceeded 10 ng/ml during or after the time of ovulation in all bitches. All bitches were bred to fertile Beagle stud dogs or inseminated with fresh semen intravaginally. Between days nine and 19 after ovulation all bitches underwent ovariohysterectomy. The uterine horns were flushed and flushes were examined for ova or embryos. The pregnancy rate in group A was 63.6% and in group B 66.7%. Despite the significantly shorter period of pre-estrus a fertile estrus could be induced in 7 out of 11 treated bitches. Induction of a fertile estrus can be achieved with a GnRH-implant-already registered for the use in male dogs-placed subcutaneously on the medial side of the leg.

Topics: Animals; Behavior, Animal; Breeding; Dogs; Estrus; Female; Gonadotropin-Releasing Hormone; Male; Ovulation Induction; Pregnancy; Pregnancy Rate; Progesterone; Triptorelin Pamoate

A 7-year-old female Bernese Mountain dog was presented for treatment to prevent oestrus. One 4.7-mg deslorelin implant was injected S/C between the shoulder blades. Three months later, the dog was re-examined because of prolonged oestrus.. Ultrasound showed multiple thin-walled cysts on both ovaries. Blood samples were taken at various intervals during the following weeks. Concentrations of oestradiol and vaginal smears indicated pro-oestrus. Follicle stimulating hormone (FSH) and luteinising hormone (LH) remained at basal concentrations.. Follicular cysts and prolonged oestrus.. Two treatments of 360 IU human chorionic gonadotrophin (hCG) were administered 42 days apart, that induced a partial or complete degeneration of the cysts. However, concentrations of oestradiol rose again within a few weeks. After the second treatment with hCG the bitch developed pyometra. After successful conservative treatment with antibiotics and aglepristone the dog underwent ovariohysterectomy.. Slow-release biocompatible implants containing deslorelin provide an opportunity for effective contraception for male dogs. Some authors describe deslorelin also as safe and efficacious for the use in female dogs but those recommendations are derived from few studies, with a small number of animals. Based on the outcome of this case and the experience of other authors we suggest a complete gynaecological examination be performed before implanting deslorelin, and weighing the risks against the advantages in controlling fertility. It is well known that the risk of induction of oestrus can be reduced when implants are administered at concentrations of progesterone in plasma of ≥16.0 pmol/L. The implant should be administered S/C, cranial and close to the umbilicus, to have the option of relocation and excision if necessary.

Topics: Animals; Chorionic Gonadotropin; Dogs; Drug Implants; Enzyme Inhibitors; Estradiol; Estrus; Female; Hysterectomy; Luteinizing Hormone; Ovarian Cysts; Ovariectomy; Progesterone; Pyometra; Reproductive Control Agents; Triptorelin Pamoate

Topics: Aggression; Animals; Bites and Stings; Enzyme Inhibitors; Humans; Lizards; Male; Testosterone; Triptorelin Pamoate

Lactation is the most energetically expensive component of reproduction in mammals. Theory predicts that reproducing females will adjust their behaviour to compensate for increased nutritional demands. However, experimental tests are required, since comparisons of the behaviour of naturally reproducing and non-reproducing females cannot distinguish between true costs of reproduction, individual differences or seasonal variation. We experimentally manipulated reproduction in free-ranging, eastern grey kangaroos (Macropus giganteus), using a fertility control agent. Our novel field experiment revealed that females altered their behaviour in direct response to the energetic demands of reproduction: reproducing females increased bite rates, and thus food intake, when the energetic demands of lactation were highest. Reproducing females did not reduce the time spent on vigilance for predators, but increased their forage intake on faecal-contaminated pasture, thereby increasing the risk of infection by gastrointestinal parasites-a largely unrecognized potential cost of reproduction.

Topics: Animals; Drug Implants; Energy Metabolism; Feeding Behavior; Female; Gastrointestinal Tract; Lactation; Luteolytic Agents; Macropodidae; Reproduction; Triptorelin Pamoate; Victoria

Topics: Animals; Drug Implants; Enzyme Inhibitors; Female; Guinea Pigs; Ovarian Cysts; Rodent Diseases; Triptorelin Pamoate

Oestrus induction in various canine breeds was attempted in 32 bitches. A group of 8 bitches were treated 80-160 d following their previous oestrus (G1) whereas a second group of 24 bitches (G2) were implanted 200-590 d following their previous oestrus. The treatment for each bitch consisted in one Deslorelin implant (Suprelorin® 4,7 mg, Virbac, France), inserted subcutaneously in the post-umbilical region. Ovulation, pregnancy rate and litter size were recorded. All bitches came in heat 4.3 ± 1.4 d after implantation (2-7 d). Ovulation was reported in 62.5% in G1 and 87.5% in G2. One bitch refused mating and since no AI was performed, she was not considered for further analysis. Pregnancy was obtained in 25% in G1 versus 78.3% in G2. Mean litter size was 6.7 ± 3.5 puppies (1-14). Luteal failure was suspected in 3 bitches, two that remained non-pregnant and one which aborted 58 d post-ovulation since the owner refused progesterone supplementation. Deslorelin implants can therefore be considered as a valuable alternative to induce fertile oestrus in bitches in anoestrus. Follow-up of the luteal phase is recommended, since some bitches might encounter luteal failure.

Topics: Animals; Dogs; Enzyme Inhibitors; Estrus; Female; Gonadotropin-Releasing Hormone; Ovulation; Pregnancy; Prostheses and Implants; Triptorelin Pamoate

Twenty-five ferret jills were randomly allocated to five groups of five animals; they were treated either before the breeding season with 15 mg medroxyprogesterone acetate (MPA), with 40 mg proligestone or with a slow-releasing device containing 4.7 mg of the gonadotropin-releasing hormone (GnRH) agonist deslorelin acetate (srGnRH), or at spring oestrus with 100 iu human chorionic gonadotropin (hCG), or were left untreated and mated. All the ferrets were assessed for signs of oestrus and their ovarian response was monitored by individual faecal progesterone metabolite (P4-met) profiles. The mean (sd) durations of treatment-induced ovarian quiescence were 94 (18), 99 (40), 53 (9) and 698 (122) days in the group treated with MPA, proligestone, hCG and srGnRH, respectively (P<0.001). Treatment with hCG and srGnRH proved to be the safest, while MPA treatment was associated with most side effects. Both MPA and proligestone treatments caused alopecia in one ferret per group, and after the first return to oestrus and mating an MPA-treated jill had a premature delivery and developed a purulent vaginal discharge. At the first post-treatment mating, the fertility (expressed as the percentage of ferrets mated in the group that produced a litter) was 75 per cent in the MPA-treated group, 60 per cent in the proligestone-treated group, 75 per cent in the hCG-treated group and 0 per cent in the srGnRH-treated group; in the control group, fertility was 100 per cent at mating in spring and 60 per cent at mating in summer. Three srGnRH-treated jills conceived at the second post-treatment oestrus.

Topics: Animals; Chorionic Gonadotropin; Contraceptive Agents, Female; Drug Implants; Estrus; Female; Ferrets; Gonadotropin-Releasing Hormone; Humans; Medroxyprogesterone Acetate; Ovulation; Pregnancy; Pregnancy Rate; Progesterone; Random Allocation; Triptorelin Pamoate

To compare the results of IVF cycles following coasting in patients treated with long versus short GnRH agonist protocols.. A retrospective comparative study in which all women aged 35 years or less attending the IVF unit from 2000 to 2006 in whom coasting was used in GnRH agonist protocols were included. Data on coasting-related variables and outcome were collected from the files and compared between the short GnRH agonist (n = 78) and long GnRH agonist (n = 181) cycles.. The short GnRH agonist cycles were characterized by higher E2 levels during coasting and longer duration of coasting than the long GnRH agonist cycles. Although the number of retrieved oocytes was lower following coasting in the short protocol, there was no difference between the groups in fertilization rate, number of high-quality embryos available for transfer, and pregnancy rate. Pregnancy rate in both protocols was negatively correlated to E2 level at initiation of coasting. The overall moderate and severe OHSS rate after coasting was 5.1% in the short-protocol group and 6.0% in the long-protocol group (p = 0.76).. The ovarian response curve to coasting is longer in the short than in the long GnRH-agonist protocol, but there is no significant difference in pregnancy or OHSS rates.

Topics: Adult; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Ovulation Induction; Pregnancy; Retrospective Studies; Statistics, Nonparametric; Treatment Outcome; Triptorelin Pamoate

Topics: Animals; Diagnosis, Differential; Dog Diseases; Dogs; Enzyme Inhibitors; Finasteride; Hemorrhage; Histocytochemistry; Male; Prostatic Hyperplasia; Triptorelin Pamoate; Ultrasonography

Immunization against GnRH has been proven effective for boar taint removal, and long-term treatment with GnRH analogues has been shown to suppress GnRH dependent reproductive processes in several species. This study was conducted to treat boars (n = 5) with Suprelorin, i.e., an implant that contains 4.7 mg of the long-acting GnRH analogue deslorelin, and to test the effects on sexual function. Insertion of the implant occurred at the age of 5 weeks and animals were observed until market age at 26-27 weeks. Surgically castrated (n = 4) and intact boars (n = 3) served as controls. Testes growth was markedly reduced and steroidogenesis (testosterone, estrone, estrone sulphate, estradiol 17beta) as well as spermatogenesis suppressed in 4 of 5 GnRH treated boars, respectively. The remaining fifth boar resumed testes growth after week 17 of age and had high hormone concentrations when tested at weeks 26 and 27. Restoration of spermatogenesis was observed at 34 weeks of age. There were no effects of treatment on general health, nor were there local inflammatory reactions. Results indicate that suppression of sexual functions in boars due to long-term treatment with the GnRH agonist deslorelin through an implant such as Suprelorin is possible and can last for several months up to market age; thus it has potential as an alternative to other methods used for boar taint removal. Because the maximum duration of suppression seems to vary between boars, further studies are necessary to refine the treatment.

Topics: Animals; Castration; Enzyme Inhibitors; Gonadal Steroid Hormones; Male; Spermatogenesis; Swine; Testis; Time; Triptorelin Pamoate

We showed previously that GnRH receptors are expressed in melanoma cells; their activation reduces cell growth and metastatic behavior. Here, we investigated whether GnRH agonists might affect the expression of genes involved in melanoma progression. By genome-wide transcriptomic and real-time PCR analysis, we first observed that GnRH agonists decrease the expression of the pro-angiogenic factor vascular endothelial growth factor (VEGF) (all isoforms) in BLM melanoma cells. Then, we demonstrated that GnRH agonists specifically decrease the expression of the VEGF165 isoform as well as its secretion from BLM cells. These data suggested that activation of GnRH receptors might reduce the pro-angiogenic behavior of melanoma cells. To verify this hypothesis, we treated BLM cells with a GnRH agonist; the conditioned medium from these cells was tested to assess its capability to stimulate human umbilical vein endothelial cell (HUVEC) motility. The migration of HUVECs towards the conditioned medium of GnRH agonist-treated BLM cells was significantly lower than the migration of HUVECs toward the conditioned medium of untreated cells. Thus, GnRH agonists reduce the pro-angiogenic behavior of melanoma cells through a decreased production of bioactive VEGF. We then found that GnRH receptors are also expressed on HUVECs and that GnRH agonists reduce their ability to proliferate and to form capillary-like tubes when stimulated by VEGF. These findings suggest that GnRH agonists exert an anti-angiogenic activity indirectly by decreasing VEGF secretion from tumor cells and directly by counteracting the pro-angiogenic activity of the growth factor. These data might lead to the development of novel targeted approaches for melanoma.

Topics: Antineoplastic Agents; Cell Proliferation; Cells, Cultured; Cluster Analysis; Drug Delivery Systems; Drug Evaluation, Preclinical; Endothelial Cells; Endothelium, Vascular; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gonadotropin-Releasing Hormone; Humans; Melanoma; Neovascularization, Pathologic; Oligonucleotide Array Sequence Analysis; Triptorelin Pamoate; Vascular Endothelial Growth Factor A

Epididymides from nine crossbred male pigs [Polish Landrace x (Duroc x Pietrain)] (n = 3 per each group) were used in this study to show whether there are any differences between androgen receptor (AR) distribution along epididymal duct of a GnRH agonist deslorelin-treated boars when compared to the control tissues. The active agent was administered by way of a subcutaneous controlled-release implant containing 4.7 mg deslorelin at 91 or 147 days of age respectively. Boars from two experimental groups and the control group were slaughtered at 175 day of age. Immunolocalization was performed using a polyclonal rabbit antiserum against the AR. In control boars, strong staining for AR was detected in nuclei of the epithelial (principal and basal) and stromal cells, whereas in boars treated with deslorelin the staining was confined to the principal cell nuclei. In those treated for 84 days, AR-immunostaining was weak or the principal cells were negative for the AR. Irrespective of the time from deslorelin insertion all stromal cells were immunonegative. The results demonstrate for the first time the effect of deslorelin on the distribution of the AR in the three regions of the boar epididymis. It is likely that stromal cells are more sensitive than epithelial cells to the regulation of AR expression by androgen. The morphological and functional alterations along the epididymal duct and lack of spermatozoa within the lumen after deslorelin treatment indicate that a potent GnRH agonist is likely responsible for an impairment of the microenvironment created by epididymal cells for sperm maturation and their storage.

Topics: Animals; Cell Nucleus; Epididymis; Epithelial Cells; Gonadotropin-Releasing Hormone; Immunohistochemistry; Male; Receptors, Androgen; Stromal Cells; Swine; Triptorelin Pamoate

Deslorelin, a luteinizing hormone releasing hormone (LHRH) agonist, is transported via the LHRH-receptor (LHRH-R) and exhibits regional variation as follows: inferior turbinate posterior (ITP)>medium turbinate posterior (MTP)>medium turbinate anterior (MTA) of the bovine nasal mucosa. Differential LHRH-R expression in various regions of the nose is a potential explanation for regional variation in deslorelin transport. Thus, the objective was to determine whether LHRH-R expression exhibits regional variation in bovine nasal mucosa. LHRH-R density (B(max)) and affinity constant (K(d)) were determined by saturation experiments using 0.5mg tissue in the presence of increasing amounts of I(125)-deslorelin (100-100,000 cpm) at 4 degrees C for 4h. The 50% inhibitory concentration (IC(50)) was determined by competition experiments using various amounts of unlabelled deslorelin (0.01-3000 ng) at 4 degrees C for 4h. LHRH-R mRNA and protein expressions were determined using real-time PCR and Western blot analysis, respectively. LHRH-R B(max) and K(d) varied between the regions of excised bovine nasal mucosa: ITP>MTP>MTA. The inhibition experiments yielded two IC(50) concentrations which exhibited trends similar to B(max) and K(d). Real-time PCR and Western blot analysis indicated that LHRH-R expression exhibits similar trends: ITP>MTP>MTA. We identified two deslorelin binding sites in the nasal tissues, with high affinity sites representing approximately 60-70% of the total sites available. In summary, regional differences in nasal deslorelin transport correlate with regional differences in LHRH-R expression, with LHRH-R expression, peptide binding, and transport being the highest in the inferior turbinate posterior region of the nose.

Topics: Animals; Biological Transport; Cattle; Gene Expression; Nasal Mucosa; Receptors, LHRH; RNA, Messenger; Triptorelin Pamoate; Turbinates

The objective was to compare the effects of eFSH and deslorelin treatment regimes on ovarian stimulation and embryo production of donor mares in early spring transition. Starting January 30th, mares kept under ambient light were examined by transrectal ultrasonography. When a follicle > or =25 mm was detected, mares were assigned to one of two treatment groups, using a sequential alternating treatment design. In the eFSH group, mares (n=18) were treated twice daily with eFSH (12.5mg im) until they achieved a follicle > or =35 mm; hCG was given 36 h later. In the deslorelin group, mares (n=18) were treated twice daily with deslorelin (63 microg im) until a follicle > or =35 mm was detected, and then they were given hCG. Estrous mares were inseminated with fresh semen. Eight days after ovulation, embryo recovery attempts were performed. In each group, 14/18 (78%) mares ovulated following the eFSH or deslorelin treatment regimes. The mean (95% CI) interval from treatment initiation to ovulation was 8.2d (7.3, 8.9) and 7.2d (6.2, 8.1) in the eFSH and deslorelin groups, respectively. In the eFSH group, the number of ovulations was significantly higher (mean+/-S.E.M.; 3.4+/-0.4 vs. 1.1+/-0.1 ovulations), and more embryos were recovered (2.6+/-0.5 vs. 0.4+/-0.2 embryos/recovery attempt). We concluded that eFSH and deslorelin treatment regimes were equally effective in inducing ovulation in early transitional mares, within a predictable time of treatment; however, the eFSH regime increased the number of ovulations and embryos recovered per mare.

Topics: Animals; Estradiol; Female; Follicle Stimulating Hormone; Horses; Insemination, Artificial; Ovarian Follicle; Ovulation Induction; Pregnancy; Progesterone; Tissue and Organ Harvesting; Triptorelin Pamoate

Docetaxel, a chemotherapeutic agent currently used for improving survival of prostate cancer patients, suffers from low therapeutic index. The objective of this study was to prepare a new docetaxel derivative conjugated to deslorelin, a luteinizing hormone-releasing hormone (LHRH) superagonist, and to determine whether it enhances docetaxel potency in vitro and in vivo. Because docetaxel is not amenable for conjugation with peptides, we introduced a -COOH group in docetaxel, forming docetaxel-hemiglutarate, and subsequently conjugated this to serine in deslorelin, forming deslorelin-docetaxel. Fourier-transform IR, (1)H-nuclear magnetic resonance, and liquid chromatography-mass spectrometry analyses confirmed deslorelin-docetaxel formation. Antiproliferative efficacy in LNCaP and PC-3 cell lines over 24, 48, and 72 hours exhibited the order deslorelin-docetaxel > docetaxel, whereas deslorelin alone had no effect, with deslorelin-docetaxel potency being 15-fold greater than docetaxel at 72 h. Further, cells pretreated with antisense oligonucleotide against LHRH receptor exhibited decreased deslorelin-docetaxel efficacy, without any change in docetaxel efficacy. Thus, deslorelin-docetaxel efficacy is likely mediated via LHRH receptor. Cell cycle analysis showed that docetaxel treatment led to arrest in G(2)-M phase, whereas deslorelin-docetaxel treatment allowed greater progression to apoptosis in both cell lines, with deslorelin-docetaxel exerting 5-fold greater apoptosis compared with docetaxel in prostate cancer cell lines. Antitumor efficacy studies in PC-3 prostate xenograft-bearing mice indicated the efficacy order deslorelin-docetaxel > docetaxel >> deslorelin > PBS, with deslorelin-docetaxel exerting approximately 5.5-fold greater tumor growth inhibition than docetaxel alone. Thus, deslorelin-docetaxel prepared in this study retains pharmacologic effects of both docetaxel and deslorelin while enhancing the antiproliferative, apoptotic, and antitumor efficacy of docetaxel by several folds in prostate cancer therapy.

Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chromatography, Liquid; Docetaxel; Dose-Response Relationship, Drug; Flow Cytometry; Humans; Magnetic Resonance Spectroscopy; Male; Mass Spectrometry; Mice; Mice, Inbred BALB C; Mice, Nude; Molecular Structure; Prostatic Neoplasms; Receptors, LHRH; Spectroscopy, Fourier Transform Infrared; Taxoids; Triptorelin Pamoate; Tumor Burden; Xenograft Model Antitumor Assays

Various combinations of gonadotropin-releasing hormone (GnRH) antagonists and long-acting GnRH agonists have been assessed in several species to prevent the "flare-up" effect that agonists cause on the pituitary-gonadal axis. To determine the effect of a single administration of the GnRH antagonist acyline in anestrous GnRH agonist-implanted domestic bitches, 19 dogs (canis familiaris) were randomly assigned to receive either 10mg sc deslorelin acetate (DA; n=6) or DA combined with 330 microg/kg sc acyline within the first 48 h (DA & ACY; n=13). These bitches were examined daily for detection of posttreatment flare-up, manifested as an estrous response during the month after treatment. In the DA and DA&ACY groups, an estrous response was detected in 6 of 6 and 9 of 12 (P<0.5) of the bitches, starting 5.3+/-1.3 and 10.1+/-1.8 d (mean+/-SEM, P=0.5), respectively, after treatment. Based on serum progesterone concentrations, ovulation occurred in 6 of 6 and 5 of 9 of these bitches (P=0.1). None of the dogs had any local or systemic side effects related to the treatments. In five DA and six DA&ACY bitches that could be followed up after the trial, interestrus intervals were 385+/-22.5 and 330+/-69.1 d, respectively (P>0.1). It was concluded that the current antagonist protocol prevented initial ovarian stimulation in one quarter of the treated dogs, whereas the stimulation period was postponed and ovulation was inhibited in approximately half of the remainder.

Topics: Anestrus; Animals; Dogs; Drug Implants; Estrus; Female; Gonadotropin-Releasing Hormone; Oligopeptides; Ovulation; Triptorelin Pamoate

The objective of this study was to determine whether surface-modified nanoparticles enhance permeability across nasal mucosa, while retaining the effectiveness of the payload. The uptake and permeability of polystyrene nanoparticles (PS-NPs; FluoSpheres) was evaluated across the various regions of the bovine nasal epithelia following conjugation with deslorelin and transferrin. Uptake and transport of PS-NPs, deslorelin-PS-NPs, and transferrin-PS-NPs exhibited regional differences in the order: inferior turbinate posterior (ITP) > medium turbinate posterior (MTP) > medium turbinate anterior (MTA). Uptake and transport also exhibited directionality and temperature dependence in these tissues. Further, uptake as well as transport of functionalized nanoparticles could be inhibited by excess free functionalizing ligand. Confocal microscopy indicated the presence of functionalized nanoparticles in respiratory epithelial cells, as well as other cell types of the nasal tissue. We chose the ITP region for further studies with deslorelin or transferrin-conjugated poly-l-lactide-co-glycolide nanoparticles (PLGA-NPs) encapsulating an anti-VEGF intraceptor (Flt23k) plasmid. Transport of the nanoparticles, as well as the plasmid from the nanoparticles, exhibited the following order: transferrin-PLGA-NPs > deslorelin-PLGA-NPs > PLGA-NPs >> plasmid. The ability of the nanoparticles transported across the nasal tissue to retain the effectiveness of the Flt23k plasmid was evaluated by measuring transfection efficiency (percentage of cells expressing GFP) and VEGF inhibition in LNCaP and PC-3 prostate cancer cells. Transfection efficiencies and VEGF inhibition in LNCaP and PC-3 cells exhibited the following trend: transferrin-PLGA-NPs >or= deslorelin-PLGA-NPs > PLGA-NPs >> plasmid. Further, functionalized nanoparticles exhibited transfection efficiencies and VEGF inhibition significantly superior compared with the routinely used transfecting agent, lipofectamine. Formulating plasmids into nanoparticulate delivery systems enhances the transnasal delivery and gene therapy at remote target cancer cells, which can be further enhanced by nanoparticle functionalization with deslorelin or transferrin.

Topics: Administration, Intranasal; Animals; Cattle; Drug Carriers; Drug Delivery Systems; Lactic Acid; Nanoparticles; Nasal Mucosa; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Transferrin; Triptorelin Pamoate

Wild Canis species such as the coyote (C. latrans) express a suite of reproductive traits unusual among mammals, including perennial pair-bonds and paternal care of the young. Coyotes also are monestrous, and both sexes are fertile only in winter; thus, they depend upon social and physiologic synchrony for successful reproduction. To investigate the mutability of seasonal reproduction in coyotes, we attempted to evoke an out-of-season estrus in October using one of two short-acting gonadotropin-releasing hormone (GnRH) agents: (1) a GnRH analogue, deslorelin (6-D-tryptophan-9-(N-ethyl-L-prolinamide)-10-deglycinamide), 2.1mg pellet sc; or (2) gonadorelin, a GnRH (5-oxoPro-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-GlyNH(2)) porcine hypothalamic extract, 2.0 microg/kg im once daily for 3 consecutive days. A transient increase in serum concentrations of estradiol and progesterone (1 and 2 wk, respectively) was detected after treatment with deslorelin but not gonadorelin. Also, socio-sexual behaviors reminiscent of winter mating (including courtship, mate-guarding, precoital mounts, and copulatory ties) were observed among the deslorelin group. During the subsequent breeding season (January and February), however, preovulatory courtship behavior and olfactory sampling appeared suppressed; emergence of mounts and copulations were delayed in both deslorelin and gonadorelin treatment groups. Furthermore, whereas 8 of 12 females treated in October ovulated and produced healthy litters in the spring, 4 naïve coyotes failed to copulate or become pregnant. Thus, perturbation of hormones prior to ovulation in species with complex mating behaviors may disrupt critical intrapair relationships, even if fertility is not impaired physiologically.

Topics: Animals; Coyotes; Estradiol; Estrous Cycle; Female; Gonadotropin-Releasing Hormone; Luteolytic Agents; Male; Progesterone; Seasons; Sexual Behavior, Animal; Triptorelin Pamoate

We tested the effect of dose of GnRH superagonist on pituitary and testicular function in a study with four groups of four male dogs. The Controls received blank implants and the other three groups received implants containing 3, 6 or 12 mg deslorelin (D-Trp6-Pro9-des-Gly10-GnRH ethylamide). In all deslorelin-treated groups, there was initially an acute increase in plasma concentrations of LH and testosterone, followed by declines such that both hormones became undetectable after approximately 12 days. There was a dose-response in some of these early aspects of the hormone profiles. With respect to long-term effects of treatment, the 12-mg dose had significantly greater effects than the smaller doses for the duration of minimum testicular volume [366 +/- 77, mean +/- SEM (3 mg), 472 +/- 74 (6 mg), and 634 +/- 59 (12 mg) days], absence of ejaculate [416 +/- 88 (3 mg), 476 +/- 83 (6 mg), and 644 +/- 67 (12 mg) days], undetectable plasma concentrations of LH and testosterone [367 +/- 64 (3 mg), 419 +/- 72 (6 mg), and 607 +/- 69 (12 mg) days], the delay until complete recovery of LH and testosterone secretion [394 +/- 65 (3 mg), 484 +/- 72 (6 mg) and 668 +/- 47 (12 mg) days], and the delay until testes had regrown to normal volume [408 +/- 77 (3 mg), 514 +/- 74 (6 mg), 676 +/- 59 (12 mg) days]. The time taken to restore full ejaculates was also longest for the 12-mg dose: 716 +/- 67 (12 mg) days vs 440 +/- 66 (3 mg) and 538 +/- 83 (6 mg) days after implantation. There was no correlation between delay to recovery of normal ejaculate quality and body mass. We conclude that the dose-response relationship with deslorelin implants is not expressed with respect to the degree of suppression of reproduction, but on the maximum duration of suppression and thus to delay until recovery.

Topics: Animals; Contraceptive Agents, Male; Dogs; Dose-Response Relationship, Drug; Drug Implants; Gonadotropin-Releasing Hormone; Kinetics; Luteinizing Hormone; Male; Pituitary Gland; Semen; Sperm Count; Sperm Motility; Testis; Testosterone; Triptorelin Pamoate

To evaluate the efficacy of a novel docetaxel derivative of deslorelin, a luteinizing hormone-releasing hormone (LHRH) agonist, and its combination in vivo with RGD peptide conjugated nanoparticles encapsulating an antiangiogenic, anti-vascular endothelial growth factor (VEGF) intraceptor (Flt23k; RGD-Flt23k-NP) in H1299 lung cancer cells and/or xenografts in athymic nude BALB/c mice.. The in vitro and in vivo efficacy of the deslorelin-docetaxel conjugate was evaluated in H1299 cells and xenografts in athymic nude mice. Coadministration of deslorelin-docetaxel conjugate and RGD-Flt23k-NP was tested in vivo in mice. Tumor inhibition, apoptosis, and VEGF inhibition were estimated in each of the treatment groups.. The conjugate enhanced in vitro docetaxel efficacy by 13-fold in H1299 cells compared with docetaxel at 24 hours, and this effect was inhibited following reduction of LHRH receptor expression by an antisense oligonucleotide. Combination of the conjugate with the RGD-Flt23k-NP in vivo resulted in an 82- and 15-fold tumor growth inhibition on day 39 following repeated weekly i.v. injections and a single intratumoral (i.t.) injection, respectively. These effects were significantly greater than individual targeted therapies or docetaxel alone. Similarly, apoptotic indices for the combination therapy were 14% and 10% in the i.v. and i.t. groups, respectively, and higher than the individual therapies. Combination therapy groups exhibited greater VEGF inhibition in both the i.v. and i.t. groups.. Docetaxel efficacy was enhanced by LHRH receptor-targeted deslorelin conjugate and further improved by combination with targeted antiangiogenic nanoparticle gene therapy. Combination of novel targeted therapeutic approaches described here provides an attractive alternative to the current treatment options for lung cancer therapy.

Topics: Animals; Cell Line, Tumor; Drug Delivery Systems; Gene Transfer Techniques; Humans; Lung Neoplasms; Medical Oncology; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Oligonucleotides, Antisense; Oligopeptides; Triptorelin Pamoate; Vascular Endothelial Growth Factor A

Holstein cows received, subcutaneously a non-degradable implant containing 5mg of the GnRH agonist Deslorelin (DESL) or no implant (CON) at 2+/-1 days postpartum (dpp). All cows were injected with PGF(2alpha) at 9 dpp. Previous pregnant (PPH) and non-pregnant uterine horns (PNPH) were determined by palpation per rectum. In Experiment 1, cows [DESL implant (n=10) and CON (n=9)] were examined by ultrasonography to record ovarian structures (23, 30 and 37 dpp) and uterine horn and cervical diameters (16, 23, 30 and 37 dpp). Uterine tone was scored before ultrasonography. Vaginoscopy was conducted just after ultrasonography examination to assess cervical discharge and color of the external cervical os. Blood samples were collected on a weekly basis for hormonal analyses. In Experiment 2, cows [DESL implant (n=77) and CON (n=70)] were palpated per rectum and vaginoscopy at 30 dpp for scoring of uterine tone, uterine horns, cervical diameter, and discharge. Blood samples were collected only at 9 dpp. In Experiment 1, DESL-implant-treated cows had more Class 1 follicles (P<0.01), less Class 2 (P<0.01) and Class 3 follicles (P<0.01) and no corpus luteum (CL) formation (P<0.01). In CON cows, six of nine animals had visible CL at 25+/-7 dpp. At 9 dpp plasma concentration of E(2), P(4) (P<0.01) and PGFM (P<0.05) were less in the DESL-implant treatment group. Diameter of PPH (P<0.01), PNPH (P<0.01) and cervix (P=0.08) were less in the DESL-implant treatment associated with greater uterine tone (P=0.07). The DESL-implant cows had a greater frequency of clear cervical discharge (P=0.09) and pink cervical os (P=0.06). In Experiment 2, plasma concentrations of PGFM were less at 9 dpp in DESL-implant treatment (P<0.01). Diameters of the PPH (P<0.01) and PNPH (P<0.01) were less and more uterine tone (P<0.01) in the DESL-implant treatment. Diameter of cervix and frequency of a cervical discharge score did not differ between treatments. Treatment with non-degradable Deslorelin (5mg) implant during postpartum: (1) suppressed ovarian follicular development, (2) enhanced physical involution of the uterus and cervix, (3) increased tone of the uterine wall, (4) decreased frequency of purulent cervical discharges, and (5) reduced inflammatory processes of the reproductive tract.

Topics: Animals; Cattle; Dinoprost; Drug Implants; Estradiol; Female; Gonadotropin-Releasing Hormone; Multivariate Analysis; Ovarian Follicle; Postpartum Period; Progesterone; Random Allocation; Statistics, Nonparametric; Triptorelin Pamoate; Uterus

The objective was to evaluate pregnancy rate to a timed artificial insemination (TAI) protocol in the autumn for cows treated with a non-degradable GnRH agonist implant (Deslorelin [DESL], 5mg) during the summer heat stress period compared with non-treated controls (CON). Cows were randomly assigned to receive or not a DESL implant within 1-4 days postpartum (dpp) twice weekly, from 25 June through 8 August 2001. All cows in DESL implant and CON treatments were injected with PGF(2alpha) 7 days after enrollment. Ultrasonography (US) monitored numbers of ovarian follicles and corpus luteum (CL) at approximately 10, 30, 35/36, 45/44, 56/55 and 66/63dpp, while DESL implants were in situ and concurrently CON, respectively. DESL implants were removed at two specific days, 28 August and 4 September. Cows had DESL implant in situ for a range of 28-67 days, depending on date of enrollment and implant removal. Within 61-100dpp, 31 days after implant removal, DESL implant and CON cows were initiated in a Presynch-Ovsynch and TAI protocol. Pregnancy was evaluated by US and palpation per rectum at 28 and 46 days after TAI, respectively. Plasma concentrations of progesterone were analyzed for sets of blood samples collected during the Presynch-Ovsynch and at TAI day followed 8 days later. Cows in the DESL-implant treatment had more (P<0.01) Class 1 (3-5mm) follicles, less (P<0.01) Class 2 (6-9mm), Class 3 (> or =10mm) follicles and CL compared with CON cows. Proportion of cows having initiated estrous cycles after calving was less (P<0.01) in the DESL-implant treatment (52.2%, 58/111) compared with CON (93.7%, 104/111) at the beginning of Ovsynch. Pregnancy rate to TAI was less (P<0.01) in the DESL implant (27.5%, 33/120) compared with CON (53.9%, 69/128). Pregnancy rate to TAI was less (P<0.01) in DESL-implanted cows that had initiated estrous cycles after calving (30.6%, 19/62) compared with CON (53.7%, 65/121) cows having initiated estrous cycles after calving. Furthermore, pregnancy rate was less (P<0.01) for cows having ovulations that had initiated estrous cycles after TAI in the DESL implant (39.1%, 18/46) compared with CON (62.1%, 54/87) treatments. Pregnancy losses from day 28 to day 46 of pregnancy did not differ between DESL implant (15.1%, 5/33) and CON (13.0%, 9/69) treatments. The DESL implant induced a delay in initiation of a new wave of follicular development during the postpartum-heat stressed period. The lesser pregnancy rate in the DESL-implant trea

Topics: Animals; Cattle; Drug Implants; Estrus Synchronization; Female; Insemination, Artificial; Lactation; Logistic Models; Ovarian Follicle; Postpartum Period; Pregnancy; Progesterone; Random Allocation; Reproduction; Triptorelin Pamoate; Ultrasonography

The aims of the present study were to examine the variability of testosterone secretion in the Virginia Opossum over a 24 h period and to develop a testosterone stimulation test that would provide an index of the prevailing testosterone biosynthetic capacity of the testes; the latter was used to clinically evaluate the efficacy of a gonadotrophin-releasing hormone agonist contraceptive. Sexually-mature captive opossums (n = 12) located in Africam Safari (Mexico) sampled every 12 h over 24 h consistently showed basal (<0.21 ng mL(-1)) blood testosterone concentrations. Intra-muscular injection of buserelin (2 microg mL(-1)) and human chorionic gonadotrophin (hCG; 1000 IU) resulted in an increase (P < 0.05) of plasma testosterone concentrations with maximal concentrations (3.9 ng mL(-1) and 5.8 ng mL(-1) respectively) occurring 120 min after injection. Plasma testosterone declined relatively rapidly to basal concentrations after 240 min with hCG but remained elevated after the same period of time with buserelin. Male opossums treated with (n = 6) and without (n = 6) a controlled-release deslorelin implant (Suprelorin; 4.7 mg deslorelin) were evaluated over a 10-week period for changes in testosterone secretion (hCG stimulation test) and sperm production (spermatorrhea). At the end of this period, the animals were hemi-castrated and their relative testicular quantitative histology compared. Testosterone concentration decreased over the course of the study in both treated and control animals (P < 0.0001) but there was no apparent effect of deslorelin on testosterone secretion, testicular histology (relative proportions of testicular cell types and seminiferous tubule diameter), or sperm production (presence of sperm in the cauda epididymis or urine).

Topics: Animals; Buserelin; Chorionic Gonadotropin; Contraception; Contraceptive Agents, Male; Diagnostic Techniques, Endocrine; Drug Evaluation, Preclinical; Drug Implants; Male; Opossums; Organ Size; Testis; Testosterone; Triptorelin Pamoate

This study was conducted to study the effects of a gonadotropin-releasing hormone (GnRH) agonist, deslorelin, on luteinizing hormone (LH), testosterone (males), semen characteristics and pregnancy in the variable flying fox Pteropus hypomelanus.. Male (n = 3) and female (n = 5) bats received a 4.7-mg implant and were housed with untreated bats (eight females and three males, respectively). Plasma was collected twice monthly and analyzed for hormone concentrations, and semen was collected from untreated and treated males 1 month preimplantation, 3 months postimplantation and 4 months postimplantation.. Administration of a GnRH challenge 1 month postimplantation showed an attenuated response in treated (n = 4), but not in untreated (n = 4), male and female bats. Plasma LH was lower in treated versus untreated males (p = .04), but not in females. Testosterone was lower in treated versus untreated males (p < .001). Spermic ejaculates were obtained from treated males, although no untreated females became pregnant during the 8-month study. One treated female became pregnant 6 months after implantation.. Deslorelin is a useful and reversible contraceptive for P. hypomelanus.

Topics: Animals; Chiroptera; Contraception; Contraceptive Agents, Female; Contraceptive Agents, Male; Female; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Male; Prostheses and Implants; Semen; Social Dominance; Testosterone; Triptorelin Pamoate

Hyperadrenocorticism in ferrets is associated with increased circulating concentrations of adrenal androgens, whereas plasma concentrations of cortisol and ACTH are usually not affected. Here, we report on a 5-year-old castrated male pet ferret (Mustela putorius furo) in which the major presenting signs were polyuria and polyphagia. Routine biochemistry values were within their reference ranges. The urinary corticoid:creatinine ratio (UCCR) was increased and the plasma ACTH concentration was suppressed. Abdominal ultrasonography revealed an enlarged right adrenal gland and atrophy of the left adrenal gland. Administration of hCG resulted in an increase of plasma cortisol and androstenedione concentrations. Based on these findings LH/hCG-dependent hypercortisolism and hyperandrogenism were suspected and treatment was started with a depot GnRH-agonist implant containing 9.4mg deslorelin. Within 3 weeks after placement of the implant all clinical signs had disappeared. Three months later the endocrine parameters had normalized, while abdominal ultrasonography revealed that the right adrenal gland had diminished in size and the left adrenal gland was considered of normal size. No recurrences of clinical signs were seen within 2 years after placement of the deslorelin implant. At that time urinary corticoid and plasma hormone concentrations were within their reference ranges, and no further change in the size of the adrenal glands was seen. In conclusion, this is the first confirmed case of LH-dependent hypercortisolism in a ferret that was treated successfully with a depot GnRH-agonist.

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Animals; Creatinine; Cushing Syndrome; Drug Implants; Ferrets; Gonadotropin-Releasing Hormone; Hydrocortisone; Luteinizing Hormone; Male; Polyuria; Triptorelin Pamoate

In this study we thoroughly scrutinized testes morphology and investigated whether treatment of recipient boars with gonadotropin-releasing hormone (GnRH)-agonist deslorelin could alter the expression of 3beta-hydroxysteroid dehydrogenase (3beta-HSD), luteinizing hormone receptors (LHRs), and androgen receptors (ARs) in testicular cells. An implant containing 4.7 mg of the GnRH-agonist deslorelin was subcutaneously inserted into crossbred male pigs at 91 and 147 days of age. Testicular traits, morphology of the testes, the proteins' expression, and testosterone concentration in blood plasma were analyzed in all boars after slaughter at 175 days of age. Histological analysis revealed significant alterations in both the interstitial tissue and seminiferous tubules of experimental animals after 28 and 84 days of deslorelin treatment. The intensity of the AR immunostaining within the testis appeared as a function of the severity of testicular dysgenesis. Time-dependent action of deslorelin on the expression of LHR and 3beta-HSD in Leydig cells was also detected. Staining for LHR and 3beta-HSD was very weak or the Leydig cells were immunonegative. Concomitantly, a significant decrease in plasma testosterone level was found in both groups of deslorelin-treated boars when compared with the control group. This is the first report showing the cellular distribution of AR, LHR, and 3beta-HSD in testicular cells of deslorelin-treated boars. It is concluded that morphological and immunohistochemical studies are important for the evaluation of testicular histoarchitecture and steroidogenic function. Subsequently, the endocrine control of reproduction in the GnRH-agonist deslorelin-treated males will be better understood.

Topics: 17-Hydroxysteroid Dehydrogenases; Animals; Gonadotropin-Releasing Hormone; Immunohistochemistry; Luteinizing Hormone; Male; Organ Size; Receptors, Androgen; Swine; Testis; Testosterone; Triptorelin Pamoate

Follicular diameter is used as a guiding tool to predict ovulation in the mare. However, the great range in preovulatory follicular diameter makes prediction of optimal breeding time based on follicular diameter unreliable. Uterine edema pattern is also useful to determine the best time to breed, since intensity of edema tends to dissipate as ovulation approaches, however, not every mare follows this pattern. The aims of this study were to assess the repeatability of preovulatory follicular diameter and uterine edema pattern in two consecutive spontaneous cycles and to determine how induction treatments (hCG, PGF(2)alpha and GnRH analogues) influence them. Fifty-three mares were followed during two consecutive cycles and scanned three times a day from 2 to 3 days before ovulation. During the first cycle, mares had a spontaneous ovulation and in the consecutive cycle mares received either: (a) no hormonal treatment; (b) 1500 IU hCG; (c) 125-250 microg Cloprostenol or (d) 2.1 mg Deslorelin implant. Mares ovulated consistently from similar follicular diameters in two consecutive spontaneous cycles (r=0.89; P<0.000). All three induction treatments had a significant effect on reducing the preovulatory follicular diameter (P<0.005). Mares showed fair correlation in uterine edema patterns in both consecutive non-induced cycles (r=0.71; P<0.005). In conclusion mares in consecutive cycles ovulated from consistent follicular diameters. Follicular diameters recorded from previous ovulations can be relied on to predict the optimal breeding time in successive cycles especially in mares that ovulate from unusually small follicles.

Topics: Animals; Chorionic Gonadotropin; Cloprostenol; Estrous Cycle; Female; Horses; Ovarian Follicle; Ovulation Induction; Triptorelin Pamoate; Ultrasonography; Uterus

Historically, artificial insemination (AI) using frozen semen has been perceived to have poorer success rates and be more labour intensive than using chilled semen. A retrospective study was therefore conducted to compare the conception rate achieved by AI between chilled and frozen semen, using fixed time insemination protocols over 2 breeding seasons.. Artificial insemination using chilled semen produces a higher conception rate than that achieved with frozen semen.. Mares (n = 251) were inseminated with either chilled (n = 112) or frozen (n = 139) semen in the 2006 and 2007 northern hemisphere breeding season. Per rectum ultrasonography of the mare's reproductive tract determined the timing of insemination, and deslorelin acetate was used to induce ovulation. Chilled semen insemination was performed using a single preovulatory dose delivered into the uterine body. Frozen semen was administered as 2 doses (pre- and post ovulation) using a deep uterine insemination technique. Pregnancy was detected ultrasonographically at 15 days post insemination. Conception rates were compared using a Chi-squared test.. Insemination with frozen semen produced a significantly (P = 0.022) higher seasonal conception rate (82.0%) than that achieved with chilled semen (69.6%).. Insemination with frozen semen can achieve conception rates equal to those with chilled semen, enabling the mare owner a greater selection of stallions.

Topics: Animals; Chi-Square Distribution; Cryopreservation; Female; Horses; Insemination, Artificial; Male; Ovulation Induction; Pregnancy; Pregnancy Rate; Retrospective Studies; Semen Preservation; Triptorelin Pamoate

The present study evaluated the effects of chronic GnRH agonist (deslorelin) treatment on sexual maturation in the male tammar wallaby. Slow-release deslorelin or placebo implants were administered to male pouch young (n = 10/group) when they were between 180 and 200 days old, to determine if disruption of the pituitary-testicular axis during development altered the timing of sexual maturation or had long-term effects on adult reproductive function. Deslorelin treatment caused retardation of testicular growth and reduced the serum FSH and testosterone concentrations between 12 and 24 mo of age. Maturation of the hypothalamic-pituitary-testicular axis was also delayed in treated animals at 13 and 19 mo of age. Despite these alterations in the pattern and timing of neuroendocrine development, sexual maturation was not permanently blocked in these animals and deslorelin-treated animals reached sexual maturity at the same age as treated animals, as evidenced by a fully functional pituitary-testicular axis and proven fertility at 25 mo of age. The ability of the treated animals to reach puberty at the same time as control animals, despite delayed maturation of the hypothalamic-pituitary-testicular axis, suggests that puberty in the male tammar wallaby is additionally regulated by other, gonadotropin-independent factors.

Topics: Animals; Body Weight; Drug Implants; Female; Fertility; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Growth and Development; Macropodidae; Male; Placebos; Reproduction; Sexual Maturation; Testis; Testosterone; Time; Triptorelin Pamoate

The present study tested whether exogenous gonadotrophin-releasing hormone (GnRH) and luteinising hormone (LH) can stimulate LH and testosterone secretion in dogs chronically treated with a GnRH superagonist. Twenty male adult dogs were assigned to a completely randomised design comprising five groups of four animals. Each dog in the control group received a blank implant (placebo) and each dog in the other four groups received a 6-mg implant containing a slow-release formulation of deslorelin (d-Trp6-Pro9-des-Gly10-LH-releasing hormone ethylamide). The same four control dogs were used for all hormonal challenges, whereas a different deslorelin-implanted group was used for each challenge. Native GnRH (5 microg kg(-1) bodyweight, i.v.) was injected on Days 15, 25, 40 and 100 after implantation, whereas bovine LH (0.5 microg kg(-1) bodyweight, i.v.) was injected on Days 16, 26, 41 and 101. On all occasions after Day 25-26 postimplantation, exogenous GnRH and LH elicited higher plasma concentrations of LH and testosterone in control than deslorelin-treated animals (P < 0.05). It was concluded that, in male dogs, implantation of a GnRH superagonist desensitised the pituitary gonadotrophs to GnRH and also led to a desensitisation of the Leydig cells to LH. This explains, at least in part, the profound reduction in the production of androgen and spermatozoa in deslorelin-treated male dogs.

Topics: Animals; Cattle; Dogs; Drug Implants; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Male; Pituitary Gland; Random Allocation; Testis; Testosterone; Triptorelin Pamoate

The present study investigated the effects of slow-release implants containing the gonadotrophin-releasing hormone (GnRH) agonist deslorelin on reproduction in the common brushtail possum (Trichosurus vulpecula). Captive female brushtail possums were assigned to control (placebo implant), low dose (4.7 mg deslorelin) or high dose (9.4 mg deslorelin) groups; males were assigned to control or high dose (9.4 mg deslorelin) groups. The acute effects of deslorelin treatment at the level of the pituitary gland were similar between the two sexes, where a transient rise in luteinising hormone concentration was induced over the first 24 h. In females, this was associated with the disruption of the normal oestrous cycle and mating within 2-10 days in some treated individuals, but no young were subsequently detected. By 3 weeks after treatment, treated females became anoestrus and remained infertile for at least one breeding season. The effects of treatment were reversible in a subset of females that had their implants removed, although the time taken to produce offspring was variable. Paradoxically, male brushtail possums remained fertile during chronic deslorelin exposure. Despite significant declines in basal follicle-stimulating hormone and testosterone concentrations, as well as an inability to respond to a GnRH challenge, treated males sired as many offspring as control males and there was no evidence of testicular regression. In conclusion, there is potential to control reproduction in female brushtail possums by using chronic GnRH agonist treatment.

Topics: Animals; Animals, Newborn; Body Weight; Contraceptive Agents; Drug Implants; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Male; Opossums; Pregnancy; Progesterone; Random Allocation; Reproduction; Testosterone; Triptorelin Pamoate

The objective of this study was to test the efficacy and safety of a short-term progestin treatment administered at two different times to prevent estrous induction in response to the administration of an implant releasing the GnRH agonist, deslorelin acetate (DA), in anestrous bitches. Interestrous intervals (IEI) observed prior to and post DA were compared. Forty-two anestrous bitches, with previous IEI history, were randomly allocated to one of the following treatments: PL: placebo sc (n = 12); MA: megestrol acetate 2mg/kg po for 8 days (n = 4); DA: 10mg sc (n = 8); MA&DA-1: MA beginning the day before DA (n = 8); and MA&DA-4: MA beginning 4 days before DA (n = 10). The dose of MA was identical for each treatment. All bitches were examined daily for 1 month and then every 3 months until the next spontaneous post-treatment estrous cycle. Post-GnRH estrous response occurred in 0, 0, 100, 50, and 10% of the PL, MA, DA, MA&DA-1, MA&DA-4, groups, respectively (<0.01). There was an interaction between the treatment and period for the duration of the IEI (< 0.01). Changes in IEI were different among treatments (p<0.01); the three DA-treated groups (147.5% +/- 10.3, 161.3% +/- 14.1, 148.6% +/- 19.2) differed from both the MA (12.9% +/- 17.6) and PL (8.1% +/- 7.8), but not among themselves. It is concluded that an 8 days megestrol protocol and DA on Day 4 was better than DA on Day 1 to prevent estrous response in anestrous bitches and that both protocols significantly increased the IEI.

Topics: Anestrus; Animals; Dogs; Estrous Cycle; Female; Gonadotropin-Releasing Hormone; Megestrol Acetate; Progestins; Random Allocation; Time Factors; Triptorelin Pamoate

Embryonic and fetal mortality reduce reproductive performance of lactating dairy cows. The objectives of this study were to reduce pregnancy loss by administering a deslorelin implant (GnRH agonist) during the late embryonic period, to reduce follicular growth, induce accessory corpora lutea, and increase plasma progesterone concentrations. Lactating dairy cows received an implant containing 2.1 mg of deslorelin (Deslorelin group; n = 89) or no treatment (Control group; n = 92) on Day 27 of pregnancy. Pregnancy, ovarian structures and plasma progesterone concentrations were determined on Days 27 and 45, and pregnancy was re-confirmed on Day 90. On Day 45, mean +/- S.E.M. numbers of class 2 (6-9 mm; 0.72+/-0.19) and class 3 (> or = 10 mm; 0.86 +/- 0.12) follicles for cows in the Deslorelin group were lower (P < 0.01) than the numbers of class 2 (1.90 +/- 0.18) and class 3 (1.92 +/- 0.12) follicles for cows in the Control group. On Day 45, the number of accessory corpora lutea for cows in the Deslorelin group (1.80 +/- 0.07) were greater (P < 0.01) than for cows in the Control group (1.31 +/- 0.07). On Day 45, plasma progesterone concentration was increased (P < 0.01) for cows in the Deslorelin group (8.03 +/- 0.33 ng/mL) compared to cows in the Control group (6.40 +/- 0.31 ng/mL). Pregnancy losses did not differ between Days 27 and 45 and Days 45 and 90 for cows in the Control (15.2 and 11.0%, respectively) and Deslorelin groups (20.2 and 10.5%, respectively). However, in the Deslorelin group, pregnancy loss between Days 45 and 90 was lower (P < 0.05) for cows that formed an accessory CL (0%) compared to cows that did not form an accessory CL (16.1%).

Topics: Abortion, Veterinary; Animals; Cattle; Corpus Luteum; Drug Implants; Female; Fertility Agents, Female; Ovarian Follicle; Pregnancy; Pregnancy, Animal; Progesterone; Random Allocation; Reproduction; Triptorelin Pamoate

Zoological institutions provide an environment conducive to studying proximate mechanisms influencing reproduction that can provide guidance to both field and captive settings seeking to manage their stock. Both national parks and zoos have space limitations that sometimes require the use of reversible contraception in order to reduce reproductive rate or limit specific individuals from reproducing. We designed a study to test the efficacy of a long-lasting contraceptive in female giraffe by monitoring reproductive endocrinology and behavior. We implanted two animals with the GnRH agonist deslorelin and monitored their endocrine status using fecal steroid analysis. We have previously validated an assay for fecal pregnanes and here we report our validation for fecal estrogens. Both sex steroid concentrations were suppressed in two females, although one female exhibited an immediate post-implantation positive feedback response. Sexual activity nearly disappeared in one animal, whereas the other showed regular sexual behavior. The contraceptive effect lasted for at least 472 d, and successfully suppressed estrous cyclicity in one female for >2 y. We conclude that deslorelin implants provide a minimally invasive means for long-term suppression of reproduction in female giraffe.

Topics: Animals; Artiodactyla; Contraceptive Agents; Drug Implants; Estrogens; Feces; Female; Fertility; Steroids; Triptorelin Pamoate

The decline in milk yield observed after peak production in dairy animals results from apoptotic death of mammary epithelial cells. In cows, this decrease in milk yield can be accelerated by injection of 17beta-estradiol, thus evoking a possible role of estrogens in the regulation of bovine mammary gland involution. In nonpregnant cows, mammary involution could be induced or enhanced by the return of estrous cycles and the accompanying cyclic peaks of estrogen concentration in the serum of lactating animals. To test this hypothesis, we inserted implants of a GnRH agonist, deslorelin, in an ear of each cow (n = 10) on d 10 and 100 of lactation, to temporarily suppress the return of ovarian cycles. Cows were studied from calving to d 210 of lactation. Deslorelin had no impact on feed intake or animal health. Deslorelin significantly reduced serum concentrations of 17beta-estradiol and progesterone as compared with untreated cows (n = 10). Deslorelin had no effect on milk fat and protein, whereas milk lactose content was lower in treated cows than in control cows on d 100 of lactation. Finally, there was no difference in milk production between the 2 groups of cows. These results are consistent with previous observations that showed that delaying estrous cycles after calving had no effect on milk yield and they extend those observations to late lactation. Based on milk production data, the estrogen profiles associated with recurring estrous cycles apparently do not cause bovine mammary tissue to undergo gradual involution.

Topics: Animals; Cattle; Drug Implants; Estradiol; Estrous Cycle; Fats; Female; Gonadotropin-Releasing Hormone; Lactation; Lactose; Milk; Milk Proteins; Progesterone; Triptorelin Pamoate

Although captive populations of endangered species such as the Mexican gray wolf (Canis lupus baileyi) can benefit from artificial insemination to accomplish genetic exchange, reliable techniques for timing insemination are lacking. We used the generic gray wolf (C. lupus) to test the efficacy of a short-acting GnRH-agonist implant, deslorelin, for inducing estrus. Of five females receiving implants on 17 or 18 January 2003, two mated naturally 10-17 days later, and the others were artificially inseminated using fresh semen, one on day 7 and all three on day 11. Relaxin tests revealed that one artificially inseminated female and both naturally mated females were pregnant on 1 March, and all three gave birth to healthy puppies on 4-6 April. Of the artificially inseminated females, only the one who subsequently conceived and gave birth was judged to be in cytologic estrus at the time of insemination. Two females were treated again with deslorelin on 12 January 2004, followed by collection of fecal samples for hormone analysis. One female, who was housed with a male, copulated on day 17 but did not conceive; the other was not with an adult male. Fecal progestin and estrogen profiles suggested that estrus, but not ovulation, was induced. These results indicated that deslorelin could induce fertile estrus in the gray wolf, although individual response varied. Further investigation is needed to better define and control the interval between implant insertion and ovulation for optimal timing of insemination.

Topics: Animals; Animals, Newborn; Drug Implants; Estrogens; Estrus; Feces; Female; Fertility Agents, Female; Fertilization in Vitro; Male; Pregnancy; Progesterone; Triptorelin Pamoate; Wolves

A novel approach to estrous induction in diestrous bitches is described. Twelve spontaneously cycling anestrous bitches served as controls. Thirteen anestrous and 15 diestrous bitches were induced to come into synchronous estrous using prostaglandin (diestrous bitches only) and deslorelin implants (Ovuplant). Implants contained either 2.1 or 1.05 mg deslorelin and were administered beneath the vestibular submucosa. All treated bitches came into estrous, regardless of implant size. Whereas all anestrous bitches ovulated, one of six diestrous bitches treated with the larger implant and three of nine treated with the smaller implant failed to ovulate. Induced bitches generally produced fewer corpora lutea than controls. Sixty-seven percent of control bitches became pregnant, with 0.63 fetuses per corpus luteum, whereas the pregnancy rate and fetuses per corpus luteum were 67 and 70% and 0.42 and 0.55 in the anestrous bitches induced with 1.05 and 2.1 mg deslorelin implants, respectively (not different from controls). Only 2 of 15 induced diestrous bitches conceived a detectable pregnancy, one of which was resorbed. In conclusion, although ovulatory estrous can be induced in bitches that had their most recent ovulation 40-100 days ago, these bitches are very unlikely to become pregnant during the induced estrous. The reason for the poor fertility in these diestrous bitches requires further study.

Topics: Animals; Corpus Luteum; Diestrus; Dinoprost; Dogs; Drug Implants; Estrus Synchronization; Female; Litter Size; Male; Ovulation Induction; Pregnancy; Progesterone; Triptorelin Pamoate

Induction of estrus with deslorelin implants was followed by abortions in bitches that conceived during the induced estrus. Lowering the deslorelin dose and choosing a better implantation site prevented the abortions. This study investigated the hypothesis that induction of estrus with deslorelin is followed by reduced serum progesterone concentrations (SPC) during the ensuing diestrus. Assuming that reduced luteal function resulted from reduced LH secretion due to hypophyseal down-regulation of GnRH receptors, the effect of human chorionic gonadotropin (hCG) treatment on the SPC of diestrous bitches was also investigated. In Experiment 1, 10 spontaneously cycling bitches served as controls, whereas estrus was induced with deslorelin implants in 24 others. In Experiment 2, six diestrous bitches were treated with a single dose of hCG between Days 39 and 45 of diestrus. The SPC was lower in deslorelin-induced bitches from Days 35 to 56 of diestrus and hCG increased SPC during the first 24 h after treatment, followed by a dramatic decline thereafter. Although SPC recovered in pregnant bitches, it remained much lower (< or = 1 ng/mL) than in untreated, non-pregnant bitches. The suppression of progesterone secretion after hCG treatment suggested that decreased luteal activity in deslorelin-induced bitches may not be a simple consequence of down-regulation of hypophyseal GnRH receptors.

Topics: Animals; Chorionic Gonadotropin; Corpus Luteum; Dogs; Drug Implants; Estrus; Female; Luteinizing Hormone; Male; Ovulation Induction; Pregnancy; Progesterone; Triptorelin Pamoate

The GnRH analogue deslorelin, as a subcutaneous implant, was initially developed in Australia as an ovulation-inducing agent in mares. Its uses, for the suppression of reproduction in the domestic dog and cat and in other species, including humans, have been developed subsequently. Such implants have been used as a contraceptive modality in a variety of wild carnivores, both males and females. This paper describes the use of deslorelin implants as a contraceptive agent for cheetah males maintained in a semi-captive environment and housed in various camps together with females. Annually, male cheetahs were treated for 1 (n = 2), 2 (n = 7), 3 (n = 9), 4 (n = 3) or 5 (n = 1) consecutive years with an implant containing 4.7, 5.0 or 6.0 mg of deslorelin. On the first day of treatment and then on an annual basis, blood testosterone concentrations were analysed, testicular measurements were taken, appearance of penile spikes was determined, and semen was collected and evaluated. Pregnancy rates of mated or inseminated females were determined. A dose of 6 mg of deslorelin suppressed reproduction for at least 1 year, whereas with 4.7 and 5 mg of deslorelin, 3 of 17 males had a few non-motile spermatozoa in their ejaculates. All testosterone concentrations were basal at 1 year post-implant and no side effects were observed. We concluded that deslorelin implantation, at a dose of 6 mg, was a safe and reliable method of annual contraception in male cheetahs.

Topics: Acinonyx; Animals; Conservation of Natural Resources; Contraception; Contraceptive Agents, Male; Drug Implants; Female; Histocytochemistry; Longitudinal Studies; Male; Statistics, Nonparametric; Testis; Testosterone; Triptorelin Pamoate

The prevention of breeding in animals using GnRH analogues has been the object of research over many years. Recently, a new drug delivery formulation was developed which enabled the development of products that could be commercialised for veterinary use. The formulation has now been approved in certain countries for use in male dogs, and applications are being expanded to cover repeat usage, extended duration, use in females, other indications and other animal species. With respect to repeat usage, dogs have been re-implanted for four consecutive doses and monitored until they returned to normal steroidogenesis. All dogs returned to normal steroidogenesis following cessation of treatment. In females, it was previously shown that implanted bitches with progesterone < 5 ng/mL at the time of implantation had an induced estrus. In a new study at Chulalongkorn University, implanting female pups at around 4 mo prevented this occurrence, whereas implantation at 7 mo did not.

Topics: Animals; Contraceptive Agents; Dogs; Drug Implants; Estrus; Female; Male; Reproduction; Testosterone; Triptorelin Pamoate

To determine whether topical ocular delivery of <100 nm nanoparticles can be enhanced by coating their exterior with peptide or protein ligands for cell surface receptors.. A novel ex vivo bovine eye model was validated for its integrity up to 60 min. Using this model, the uptake of 20 nm polystyrene nanoparticles (administered as a single 50 mul drop) before and after surface conjugation with deslorelin, a luteinizing hormone-releasing hormone (LHRH) agonist, or transferrin was determined at 5 and 60 min in individual layers of cornea and aqueous humor. Selected studies were done in the absence of corneal epithelium in the ex vivo model or using excised cornea and conjunctiva. LHRH and transferrin receptor mRNA and protein expression in corneal epithelium and conjunctiva were determined by real-time PCR and western blot, respectively.. Corneal histology, ZO-1 immunostain pattern, and mannitol permeability were similar in controls and at the end of the ex vivo study. Corneal epithelial nanoparticle uptake in the absence of surface modification was 1.1-1.6% at 5 min and remained at about this level even at 60 min. Removal of the corneal epithelium resulted in about 22% particle uptake in the corneal stroma at 5 and 60 min compared to about 0.5% in the presence of epithelium, indicating the barrier nature of corneal epithelium. Deslorelin and transferrin conjugation enhanced corneal epithelial uptake of nanoparticles by 3- and 4.5 fold at 5 min and by 4.5- and 3.8 fold at 60 min, respectively. The total corneal uptake in 5 min is approximately 2.4, 9, and 16% with plain, deslorelin-functionalized, and transferrin-functionalized nanoparticles. In all groups, the nanoparticle uptake per unit tissue weight was in the order: corneal epithelium>stroma>endothelium with levels in the aqueous humor being undetectable. In excised cornea and conjunctiva studies, nanoparticle transport and uptake was elevated for both deslorelin and transferrin conjugated nanoparticles. Expression of LHRH and transferrin receptors was observed in corneal epithelium as well as conjunctiva.. The ex vivo bovine eye model is a useful tool in understanding disposition of nanoparticles after topical delivery. The corneal epithelium is a significant barrier for topical nanoparticle delivery to the anterior segment. Surface modification of nanoparticles by conjugating an LHRH agonist or transferrin is a useful approach to provide rapid, efficient delivery of intact nanoparticles into and/or across cornea and conjunctiva.

Topics: Animals; Biological Transport; Cattle; Chemical Phenomena; Chemistry, Physical; Conjunctiva; Cornea; Epithelium, Corneal; Eye; Gonadotropin-Releasing Hormone; Microscopy, Confocal; Nanoparticles; Ophthalmic Solutions; Receptors, LHRH; Receptors, Transferrin; RNA, Messenger; Transferrin; Triptorelin Pamoate

To minimize the number of matings/inseminations, controlled ovulation has been practised since a long time ago. A potent short-term implant, releasing the GnRH analogue deslorelin (Ovuplant((R))) has been used in Australia and North America for several years for hastening the ovulation time in mares, but the product is not registered on the European market. This study was aimed to investigate: (1) ovulation time in mares implanted with Ovuplant when the largest follicle was 42 mm or more in size, (2) repeatability of ovulation time in successive oestruses when treated with Ovuplant, (3) pregnancy rate after single insemination with frozen-thawed semen near ovulation. This study included 11 mares, and altogether 17 timed ovulations. Follicular growth and ovulation were determined by palpation per rectum and by ultrasonography in the morning (at 7:00 hours) every second day until observation of a follicle of at least 42 mm in diameter. Then the mares were re-examined in the afternoon (at 19:00 hours), and an Ovuplant was inserted in the mucosa of the vulva. For detection of ovulation, the mares were palpated and ultrasounded repeatedly from 36-42 h after the insert. The mares were inseminated with frozen-thawed semen once at ovulation. All mares ovulated at 36-48 h after treatment and 94% at 38-42 h after treatment. The six mares that were treated at two oestruses ovulated at 39.9 and 39.7 h, respectively. Five of 11 mares (45.4%), inseminated with frozen-thawed semen at the first oestrous cycle were pregnant day 14-16 after ovulation. Using this protocol, there is no need of palpation/ultrasonography during night hours, and examination at 36 and 41 h after implantation might be enough for estimation of ovulation time.

Topics: Animals; Cryopreservation; Digital Rectal Examination; Enzyme Inhibitors; Female; Gonadotropin-Releasing Hormone; Horses; Insemination, Artificial; Ovulation; Ovulation Detection; Ovulation Induction; Pregnancy; Pregnancy Outcome; Pregnancy Rate; Reproducibility of Results; Semen Preservation; Time Factors; Triptorelin Pamoate

The contraceptive and endocrine effects of long-term treatment with implants containing the GnRH agonist deslorelin were investigated in female tammar wallabies (Macropus eugenii). Fertility was successfully inhibited for 515 +/- 87 days after treatment with a 5 mg deslorelin implant (n = 7), while control animals gave birth to their first young 159 +/- 47 days after placebo implant administration (n = 8). The duration of contraception was highly variable, ranging from 344 to 761 days. The strict reproductive seasonality in the tammar wallaby was maintained once the implant had expired. This inhibition of reproduction was associated with a significant reduction in basal LH concentrations and a cessation of oestrous cycles, as evidenced by low progesterone concentrations. There was evidence to suggest that some aspect of either blastocyst survival, luteal reactivation, pregnancy or birth may be affected by deslorelin treatment in some animals. These results show that long-term inhibition of fertility in the female tammar wallaby is possible using slow-release deslorelin implants. The effects of deslorelin treatment were fully reversible and there was no evidence of negative side effects. Slow-release GnRH agonist implants may represent a practicable method for reproductive management of captive and semi-wild populations of marsupials.

Topics: Animals; Contraceptive Agents; Delayed-Action Preparations; Drug Implants; Female; Fertility; Luteinizing Hormone; Macropodidae; Progesterone; Seasons; Time Factors; Triptorelin Pamoate

The objectives of this study were: to compare the recovery of follicular development in early postpartum cows that had been treated for 7, 14 or 21 d with implants containing the GnRH agonist deslorelin; to evaluate the effectiveness of human chorionic gonadotrophin (hCG) for the induction of ovulation when a follicle was at least 10 mm in diameter following implant removal; and to compare final pregnancy rates for treated cows and untreated contemporaries.. Within 3 d of calving Holstein cows were allocated to receive a single subcutaneous deslorelin implant to be left in place for either 7, 14 or 21 d, or to remain untreated as controls. Every deslorelin treated cow was monitored twice weekly for 35 d to determine the interval from implant removal to resumption of ovulation using serial transrectal ultrasonography and plasma progesterone assay. An injection of 1000 IU hCG was given to induce ovulation when a follicle of at least 10 mm diameter was first observed. Oestrous cycles of every cow were synchronised to facilitate artificial insemination (Al) at the start of the seasonally concentrated Al program and resynchronised for three rounds. Pregnancy testing was performed by ultrasonography 13 weeks after the first round of Al.. Deslorelin implants inhibited ovulation for at least 10 d after they were removed. Ovarian follicles were smaller for the group that had implants for 21 d at the time of implant removal. Eighteen cows selected for treatment with hCG ovulated and formed multiple corpora lutea within 7 d. There was no effect of treatment duration on final pregnancy rates. After three rounds of AI the pooled final pregnancy rate for every cow that had received a deslorelin implant was similar to the rest of the herd (67% versus 63%; Deslorelin versus Herd, P > 0.1). The interval from start date of the AI program to conception was also unaffected by treatment (9.6 +/- 3.0 versus 14.8 +/- 1.7 d; Deslorelin versus Herd; P > 0.1).. No significant effect was detected on the interval from implant removal to first ovulation by altering the duration of deslorelin treatment. Treatment with hCG when a follicle at least 10 mm in diameter was present induced ovulation in most cases. Although no significant improvement in fertility was found, a larger field trial using this model for induced anoestrous is necessary before any effect on fertility could confidently be stated.

Topics: Animals; Cattle; Chorionic Gonadotropin; Drug Implants; Estrus; Estrus Synchronization; Female; Gonadotropin-Releasing Hormone; Ovarian Follicle; Ovulation; Postpartum Period; Pregnancy; Pregnancy Rate; Progesterone; Random Allocation; Reproduction; Time Factors; Triptorelin Pamoate

Continuous GnRH agonist treatment of cows results in downregulation of GnRH responsiveness and a state of induced anoestrus. Inducing anoestrus in a precisely controlled manner could have several potential applications in dairy herd management. However, relatively little is known regarding the processes involved in restoring reproductive normality following an induced anoestrus. This study describes an experiment that was conducted to examine patterns of recovery of LH release and follicle growth in non-lactating Holstein cows immediately following cessation of treatment for 7, 14 or 21 days with a deslorelin implant. Oestrus cycles were synchronized at 7 days intervals and a deslorelin implant inserted in every cow 13 days after detected oestrus so that a group had implants for either 21 days (n = 9), 14 days (n = 10) or 7 days (n = 9). On the day of implant removal every ovarian follicle greater than 4 mm in diameter was ablated using ultrasound guided vacuum needle aspiration in an attempt to standardize follicle sizes. Daily ovarian ultrasound examinations were performed on each cow until 35 days after implant removal and again at 45, 59 and 74 days. A subgroup of four cows randomly selected from each treatment group had frequent serial blood samples collected over 8 h at 4 and 10 days after implant removal for LH profiling. There was no significant effect of treatment duration on any LH parameter and results were pooled. Mean LH pulse amplitude increased by 67% between 4 and 10 days after implant removal (0.34 ng/ml versus 0.57 ng/ml; 4 days versus 10 days post-implant, P < 0.001). Mean pulse frequency remained unchanged between the two samplings (5.9 pulses versus 6.9 pulses per 8 h; 4 days versus 10 days post-implant, P > 0.1). Smoothed mean LH concentrations were unaffected by treatment duration or time (0.36 ng/ml versus 0.41 ng/ml; 4 days versus 10 days post-implant, P > 0.1). The pattern of follicle growth and ovulation did not differ significantly between treatment durations and pooled means were used for comparative descriptions. The emergence of a new follicle wave could be detected beginning at 4 days after implant removal (mean 7.9 +/- 0.8 days). After emergence, a period of rapid follicle growth generally ensued with signs of oestrus occurring when the follicle reached 12.3 +/- 0.5 mm and ovulation when mean follicle diameter was 13.1 +/- 0.7 mm at 13.6 +/- 1.5 days after implant removal. Oestrus preceded ovulation in all cases where ovul

Topics: Animals; Cattle; Drug Implants; Estrous Cycle; Estrus Synchronization; Female; Luteinizing Hormone; Ovarian Follicle; Ovary; Ovulation; Triptorelin Pamoate; Ultrasonography

The objective was to compare testis characteristics of Zebu bulls treated with the GnRH agonist, deslorelin, at different times and for different durations during their development. An additional objective was to determine the usefulness of a stain for the transcription factor GATA-binding protein 4 (GATA-4) as a specific marker for Sertoli cell nuclei in cattle. Bulls (54) were allocated to nine groups (n = 6) and received s.c. deslorelin implants as follows: G1 = from birth to 3 mo of age; G2 = from 3 to 6 mo; G3 = from 6 to 9 mo; G4 = from 9 to 12 mo; G5 = from birth to 15 mo; G6 = from 3 to 15 mo; G7 = from 6 to 15 mo; G8 = from 12 to 15 mo; and G9 (control) = no implant. Bulls were castrated at 19 mo of age. Paraffin sections (10 microm) were subjected to quantitative morphometry and GATA-4 immunohistochemistry. At castration, all bulls in the control group (6/6) had attained puberty (scrotal circumference > or = 28 cm), whereas a smaller proportion (P < 0.05) had reached puberty in G2 (2/5) and G6 (1/6). Bulls in G2 and G6 also had a lesser (P < 0.05) testis weight compared with the control group. Total volume of seminiferous epithelium and total daily sperm production in G2 and G6 were only half that observed in the control group. Spermatids were observed in less than 50% of seminiferous tubules in G2, G6, and G7 compared with 82% in the control group (P < 0.05). Staining for GATA-4 was specific for and abundant in the Sertoli cell nucleus in both pre- and postpubertal bulls, and no other cell nucleus inside the seminiferous tubule was positive for GATA-4. Total number of Sertoli cells was not affected by treatment (P = 0.45), but nuclear volume was smaller in G2 and G6 (P < 0.05) compared with the control group. In conclusion, treatment of Zebu bulls with deslorelin had no apparent beneficial effect on testis development and delayed puberty when treatment was initiated at 3 mo of age. Staining for GATA-4 was a useful method for identifying and quantifying Sertoli cell nuclei in both pre- and postpubertal bulls.

Topics: Animals; Antibodies; Body Weight; Cattle; Enzyme Inhibitors; GATA4 Transcription Factor; Gonadotropin-Releasing Hormone; Male; Orchiectomy; Radioimmunoassay; Scrotum; Seminiferous Epithelium; Sertoli Cells; Testis; Time Factors; Triptorelin Pamoate

The objective of this study was to evaluate ovarian function after inducing ovulation with a deslorelin implant in nonlactating dairy cows and heifers. Cattle received GnRH on Day -9, and PGF2alpha on Day -2. On Day 0, in Experiment 1, cows received either 100 microg GnRH (Control), a 750 microg (DESLORELIN 750) or 1000 microg (DESLORELIN 1000) deslorelin implant. On Day 0, in Experiment 2, cows received 100 microg of GnRH or a 450 microg (DESLORELIN 450) deslorelin implant. In Experiments 1 and 2, cows received PGF2alpha on Day 16. Ultrasonography and blood sampling for plasma progesterone (P4) were used to monitor ovarian activity. On Day 0, in Experiment 3, heifers received either 100 microg of GnRH or 750 microg (DESLORELIN 750) deslorelin implant. On Day 16, all heifers received PGF2alpha. Blood samples were collected on Days 7, 13 and 16. In Experiments 1-3, deslorelin implants did not elevate plasma concentrations of P4 in a systematic manner during the late luteal phase. In Experiments 1 and 2, deslorelin implants decreased the size of the largest follicle and the number of Class II and III follicles. In Experiments 1 and 2, deslorelin-treated cows failed to ovulate by Day 28. In conclusion, deslorelin implants induced ovulation, stimulated development of a normal CL, and delayed follicular growth during the subsequent diestrus period. For future applications, the dose of the deslorelin implant will have to be adjusted, and if used for timed-inseminations, nonpregnant cows will have to be resynchronized to minimize delayed returns to estrus and ovulation.

Topics: Animals; Cattle; Corpus Luteum; Dinoprost; Drug Implants; Female; Gonadotropin-Releasing Hormone; Ovarian Follicle; Ovary; Ovulation Induction; Progesterone; Triptorelin Pamoate; Ultrasonography

This study examined the influence of a GnRH agonist containing either 450 or 750 microg of deslorelin in an implant form or a gonadorelin injection (control) to induce ovulation in the Ovsynch protocol on pregnancy rates (PR), embryonic loss, and ovarian function in 593 lactating Holstein cows. Cows were given two injections of PGF2alpha 14 days apart, followed 14 days later by the Ovsynch protocol, and were timed artificially inseminated (TAI) at 68 +/- 3 days postpartum. Blood samples for determination of plasma progesterone concentrations were collected at 24 and 10 days prior to and 11 days after TAI. Pregnancy was diagnosed on Day 27 and reconfirmed on Day 41 after TAI. Non-pregnant, not re-inseminated cows at Day 27 had their ovaries examined by ultrasonography, and the number and size of follicles and presence of luteal tissue were determined. Simultaneously, these cows were re-synchronized with the Ovsynch protocol. Pregnancy during the re-synchronization period was determined between 35 and 41 days after insemination. On Day 27, PR were higher for control (39.0%) and deslorelin 450 microg (DESLORELIN 450) implant (41.3%) than for those receiving the deslorelin 750 microg (DESLORELIN 750) implant (27.5%; P<0.05). Pregnancy losses tended to decrease for DESLORELIN 450 compared with control (5.0% versus 12.7%; P<0.13). Plasma progesterone concentrations did not differ significantly among treatments. Deslorelin suppressed ovarian activity and decreased PR during the re-synchronization period compared with control. The percentage of non-pregnant animals that were re-inseminated by Day 27 was less for deslorelin compared with control. In conclusion, incorporation of an implant of the GnRH agonist deslorelin to induce ovulation in the Ovsynch protocol has the potential to reduce pregnancy losses, but the response was dependent upon implant concentration. Evaluation of lower doses to minimize the negative effects on subsequent fertility is warranted.

Topics: Abortion, Veterinary; Animals; Cattle; Corpus Luteum; Dinoprost; Drug Implants; Estrus Synchronization; Female; Insemination, Artificial; Lactation; Ovarian Follicle; Ovary; Pregnancy; Progesterone; Reproduction; Time Factors; Triptorelin Pamoate; Ultrasonography

In children with precocious puberty (PP), treatment with GnRH analogs (GnRHa) often decreases height velocity below normal. Based on previous animal studies, we hypothesized that this impaired growth is due to excessive advancement in growth plate senescence induced by the prior estrogen exposure. This hypothesis predicts that the height velocity during treatment will be inversely related to the severity of prior estrogen exposure. We analyzed data from 100 girls (age, 5.8 +/- 2.1 yr; mean +/- SD) with central PP who were treated with GnRHa. During GnRHa therapy, height velocity was low for age (-1.6 +/- 1.7 SD score; mean +/- SD). The absolute height velocity correlated most strongly with the bone age (BA), which we used as a surrogate marker for growth plate senescence (r = -0.727, P < 0.001). The severity of the growth abnormality (height velocity SD score for age) correlated inversely with markers of the severity of prior estrogen exposure, including duration of PP (r = -0.375, P < 0.001), Tanner breast stage (r = -0.220, P < 0.05), and BA advancement (r = -0.283, P < 0.01). Stepwise regression confirmed that BA was the best independent predictor of growth during GnRHa therapy. The findings are consistent with our hypothesis that impaired growth during GnRHa therapy is due, at least in part, to premature growth plate senescence induced by the prior estrogen exposure.

Topics: Age Determination by Skeleton; Body Height; Child; Child, Preschool; Estrogens; Female; Gonadotropin-Releasing Hormone; Growth Disorders; Growth Plate; Humans; Puberty; Puberty, Precocious; Regression Analysis; Time Factors; Triptorelin Pamoate

This study evaluated the potential of slow-release GnRH agonist (deslorelin) implants to inhibit reproductive function in the male tammar wallaby. The specific aim was to measure the effects of graded dosages of deslorelin on testes size and plasma LH and testosterone concentrations. Adult male tammar wallabies were assigned to four groups (n = 6 per group) and received the following treatment: control, placebo implant; low dose, 5 mg deslorelin; medium dose, 10 mg; high dose, 20 mg. All dosages of deslorelin induced acute increases (P < 0.001) in plasma LH and testosterone concentrations within 2 h, with concentrations remaining elevated during the first 24 h but returning to pretreatment levels by Day 7. Thereafter, there was no evidence of a treatment-induced decline in plasma testosterone concentrations. There was no detectable difference in basal LH concentrations between treated and control animals, nor was there a significant change in testes width or length (P > 0.05). These results suggest that the male tammar wallaby is resistant to the contraceptive effects of chronic GnRH agonist treatment. Despite the maintenance of testosterone secretion, the majority of male tammars (10 of 17) failed to respond to a GnRH challenge with a release of LH between Days 186 and 197 of treatment. The failure of animals to respond to exogenous GnRH suggests a direct effect of deslorelin on the pituitary, resulting in a level of desensitization that was sufficient to inhibit a LH surge but insufficient to inhibit basal LH secretion. The variation between animals is believed to result from earlier recovery of some individuals, in particular those that received a lower dose, or individual resistance to the desensitization process.

Topics: Animals; Drug Implants; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Macropodidae; Male; Pituitary Gland; Reproduction; Species Specificity; Testis; Testosterone; Time Factors; Triptorelin Pamoate

The effect of treatment with slow release implants containing the GnRH agonist, deslorelin, was investigated in female tammar wallabies. Pouch young were removed from 16 wallabies presumed to be carrying quiescent blastocysts. Eight received a 5 mg deslorelin implant and eight received a placebo implant. Animals were caught daily from day 25 to day 30 and their pouches inspected for newborn young and their urogenital sinus checked for a copulatory plug. Treatment with deslorelin did not affect reactivation of a dormant blastocyst and subsequent birth in 4/8 animals, but post-partum mating was inhibited in these animals. Five control and five treated animals were killed within 0-48 h post partum and their reproductive tracts analysed. At autopsy, all five control animals had large preovulatory follicles but only one deslorelin-treated animal showed signs of follicular development. These differences were also reflected in the weights of the lateral vaginae, with treated animals showing no evidence of oestrogenic stimulation. The remaining three control and three treated animals were monitored for approximately 2 years. The long-term contraceptive effects of a single 5 mg deslorelin implant lasted for just under one year. These results indicate that slow release deslorelin implants inhibit follicular development in the female tammar wallaby for extended periods of time and may have potential application in reproductive management of captive marsupials in the kangaroo family.

Topics: Animals; Contraception; Contraceptive Agents; Delayed-Action Preparations; Drug Implants; Embryo Implantation, Delayed; Estrus; Female; Genitalia, Female; Labor, Obstetric; Macropodidae; Ovarian Follicle; Pregnancy; Time Factors; Triptorelin Pamoate

Practical estrus synchronization schemes are needed for mares. The Ovsynch synchronization protocol for cattle involves the administration of gonadotropin-releasing hormone (GnRH) to induce ovulation or luteinization of dominant follicles during the luteal phase and prostaglandin 7 days later to cause regression of any luteal tissue and development of a preovulatory follicle. An Ovsynch-type synchronization program potentially could be developed for horses if luteinization or ovulation of diestrous follicles occurred in response to GnRH treatment. The objective of this study was to determine if administration of the GnRH agonist, deslorelin acetate, on Day 8 or 12 postovulation would induce luteinization or ovulation of diestrous follicles in the mare. The model used was cycling mares maintained in an artificial luteal phase by administration of a synthetic progestin following prostaglandin-induced luteal regression. On the day of ovulation, 21 light horse mares were randomly assigned to one of three groups: (1) no GnRH, altrenogest from Days 5 to 15 postovulation with prostaglandin on Day 15; (2) GnRH on Day 8, altrenogest from Days 5 to 15 with prostaglandin given on Day 6 to induce luteolysis of the primary corpus luteum, an implant containing 2.1mg of deslorelin acetate inserted on Day 8 and removed on Day 10, with a second prostaglandin treatment on Day 15; (3) GnRH on Day 12, altrenogest from Days 9 to 19, prostaglandin on Day 10, a deslorelin acetate implant injected on Day 12 (subsequently removed on Day 14), and a second dose of prostaglandin administered on Day 19. Follicular development was monitored every other day from Day 5 until a 30-mm sized follicle was observed, and then daily to detection of ovulation. Serum progesterone concentrations were determined daily for 12 consecutive days. Progesterone concentrations in Group 1 remained elevated until approximately Day 12 postovulation. Prostaglandin administration on Day 15 resulted in complete luteolysis in all seven mares. In Group 2, progesterone concentrations in six of seven mares declined to baseline after prostaglandin treatment. No increase in serum progesterone was noted in any of the six mares that were given GnRH on Day 8, including three mares that had diestrous follicles > or =30mm in diameter at the time of treatment. Similarly, progesterone concentrations in six of seven mares in Group 3 declined to baseline after prostaglandin and there was no increase in progesterone after adm

Topics: Animals; Cloprostenol; Diestrus; Drug Implants; Estrus Synchronization; Female; Gonadotropin-Releasing Hormone; Horses; Luteinization; Luteolysis; Ovarian Follicle; Ovulation; Progesterone; Trenbolone Acetate; Triptorelin Pamoate

To determine whether LHRH-receptor is expressed in Calu-3, a human bronchial epithelial cell line, and to further determine whether this receptor plays a role in the transport of deslorelin, an LHRH agonist.. Using cultured monolayers of Calu-3 grown at air-interface, the presence and localization of LHRH-receptors in Calu-3 cells was determined using immunochemical methods. To determine the mechanisms of deslorelin transport, the directionality [apical-basolateral (A-B) and basolateral-apical (B-A)] of deslorelin transport across Calu-3 monolayers and the effects of temperature (37 degrees C and 4 degrees C) and an energy depletor (2,4-dinitrophenol) were investigated. To determine the role of LHRH-receptor in deslorelin transport across Calu-3 monolayers, the influence of an LHRH-receptor antisense oligonucleotide on the LHRH-receptor expression and deslorelin transport was studied. Also, the effect of a competing LHRH agonist, buserelin, on deslorelin transport was determined.. Immunofluorescence studies indicated the predominance of LHRH-receptor in Calu-3 cells at the apical and lateral surfaces. Western blot and RT-PCR studies further confirmed the expression of LHRH-receptor in Calu-3 cells. Deslorelin transport across Calu-3 monolayers was vectorial, with the cumulative A-B transport (1.79 +/- 0.29%) at the end of 240 min being higher than the B-A transport (0.34 +/- 0.11%). Low temperature as well as 2,4-dinitrophenol abolished this directionality. LHRH-receptor antisense oligonucleotide decreased the receptor expression at the mRNA and protein level and reduced the A-B deslorelin transport by 55 +/- 4%, without affecting the B-A transport, suggesting a role for LHRH-receptor in the vectorial transport of deslorelin. In addition, buserelin reduced the A-B deslorelin transport by 56 +/- 5% without affecting the B-A transport.. Taken together, our results provide evidence that deslorelin is transported across the respiratory epithelium via the LHRH-receptor.

Topics: 2,4-Dinitrophenol; Animals; Biological Transport; Blotting, Western; Buserelin; Cattle; Cell Line; Electric Impedance; Epithelial Cells; Fluorescent Antibody Technique; Gene Expression; Humans; Oligoribonucleotides, Antisense; Rats; Receptors, LHRH; Respiratory System; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Temperature; Time Factors; Triptorelin Pamoate

The nasal route is a non-invasive alternative route for the delivery of a number of macromolecules, including peptides, proteins and vaccines. The purpose of this study was to determine the regional variation in excised bovine nasal tissue permeability to deslorelin, a nonapeptide luteinizing hormone releasing hormone (LHRH) agonist, and to further elucidate its mechanisms of transport. To this end, this study determined the permeability of deslorelin across different regions of freshly excised bovine nasal mucosa, including the medium turbinate anterior (MTA), medium turbinate posterior (MTP) and the inferior turbinate posterior (ITP) regions. At 37 degrees C, mucoal-to-serosal (m-s) transport of deslorelin across excised bovine nasal mucosa exhibited regional variation, with the % cumulative transport in 6 h being in the order: MTA (0.2 +/- 0.06%) < MTP (1.6 +/- 0.1%) < ITP (2.85 +/- 0.3%). In addition, at 37 degrees C, deslorelin transport across all these nasal regions was vectorial and the mucosal-to-serosal:serosal-to-mucosal (m-s:s-m) transport ratios across MTA, MTP and ITP regions were 1.5, 5.4 and 3.7, respectively. At low temperature (4 degrees C) and at 37 degrees C in the presence of 2,4-dinitrophenol, an energy depletor, the m-s deslorelin transport across the MTP region decreased to 0.32 +/- 0.12 and 0.13 +/- 0.05%, respectively, and the directionality was abolished. Sodium fluorescein transport also exhibited regional variation but no directionality. Histology and scanning electron microscopy studies indicated non-ciliated columnar epithelium in the MTA region and ciliated respiratory epithelium in the MTP and ITP regions. The thickness of the various regions, as visualized using histology, was in the order: MTA > MTP > ITP. Thus, deslorelin transport across excised bovine nasal mucosa is vectorial, temperature- and energy-dependent and exhibits regional variation. The regional differences in s-m transport are likely due to differences in the passive transport. Differences in m-s:s-m flux ratios may be due to differential expression of carriers.

Topics: Animals; Biological Transport; Cattle; Cell Membrane Permeability; Enzyme Inhibitors; In Vitro Techniques; Microscopy, Electron, Scanning; Nasal Mucosa; Temperature; Triptorelin Pamoate; Turbinates

Mares treated with subcutaneous deslorelin implants on the first postpartum estrus early in the breeding season had significant reductions in the number of large follicles at early pregnancy examinations and delayed return to estrus (in mares that failed to become pregnant); these adverse effects were attributed to a prolonged release of the drug from the implant. In 2003, an injectable short-term release (<24 h) deslorelin product became available. The objective of this study was to determine if this product would hasten ovulation in early foaling first postpartum estrus mares without reducing the number of large follicles at early pregnancy examination (14-15 days postovulation). Beginning 5-6 days postpartum, first postpartum estrus (foal-heat) mares were teased daily and examined thrice weekly (Tuesday, Thursday and Saturday) by transrectal ultrasonography. Mares in estrus with a follicle > or = 34 mm diameter on Tuesdays or Thursdays were alternately assigned to: Treatment 1, n = 17; 1.5 mg injectable short-term release deslorelin, or Treatment 2, n = 16; Control (no treatment). The schedule allowed accurate determination of the number of mares ovulating within 2 days of treatment (i.e., ovulations detected on Thursday or Saturday). Mares were mated on the day of treatment and at 2-day intervals until either ovulation was confirmed or until behavioral estrus ceased. Transrectal ultrasonography was done 14-15 days after ovulation to assess ovarian follicles and pregnancy status. Fewer covers were required and more mares ovulated within 2 days of treatment in deslorelin-treated versus Control mares (P < 0.01). Pregnancy rates were normal (69%) in deslorelin-treated mares. The number of large follicles 14-15 days after ovulation did not differ between deslorelin-treated and Control mares (P > 0.10), suggesting follicular suppression did not occur with this formulation of deslorelin.

Topics: Animals; Breeding; Drug Implants; Estrus; Female; Horses; Injections; Ovarian Follicle; Ovulation Induction; Postpartum Period; Pregnancy; Triptorelin Pamoate; Ultrasonography

To compare the systemic delivery of deslorelin following intratracheal administration of different deslorelin formulations. The formulations included dry powders of deslorelin, large-porous deslorelin-poly(lactide-co-glycolide) (PLGA) particles, and small conventional deslorelin-PLGA particles. Also, solution formulations of deslorelin and deslorelin-hydroxy-propyl-beta-cyclodextrin (HPbetaCD) complexes were tested.. Dry powders of deslorelin, large-porous (mean diameter, 13.8 microm; density, 0.082 g/cc), and small conventional (mean diameter, 2.2 microm; density, 0.7 g/cc) deslorelin-PLGA particles and solutions of deslorelin with or without HPbetaCD were administered intratracheally to Sprague-Dawley rats. Blood samples were collected at 3 h, 1, 3, and 7 days postdosing, and plasma deslorelin concentrations were determined using enzyme immunoassay. At the end of 7 days, lungs were isolated, and bronchoalveolar lavage fluid was collected and analyzed for deslorelin.. At the end of 7 days, deslorelin plasma concentrations in the large-porous deslorelin-PLGA particle group were 120-fold and 2.5-fold higher compared to deslorelin powder and small conventional deslorelin-PLGA particles, respectively. Co-administration of HPbetaCD resulted in 2-, 3-, and 3-fold higher plasma deslorelin concentrations at 3 h, 1 and 3 days, respectively, compared to deslorelin solution. On day 7, deslorelin concentrations in bronchoalveolar lavage fluid as well as plasma were in the order: large porous particles > small conventional particles > deslorelin-HPbetaCD solution > deslorelin powder > deslorelin solution.. Large-porous deslorelin PLGA particles can sustain deslorelin delivery via the deep lungs. Co-administration of HPbetaCD enhances the systemic delivery of deslorelin. The pulmonary route is useful as a noninvasive alternative for the systemic delivery of deslorelin.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Administration, Inhalation; Animals; beta-Cyclodextrins; Bronchoalveolar Lavage Fluid; Drug Carriers; Lactic Acid; Lung; Male; Particle Size; Pharmaceutical Solutions; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Porosity; Powders; Rats; Rats, Sprague-Dawley; Trachea; Triptorelin Pamoate

Topics: Adolescent; Body Height; Bone Density; Child; Enzyme Inhibitors; Gonadotropin-Releasing Hormone; Growth Disorders; Humans; Puberty; Triptorelin Pamoate

The objective of this study is to investigate the pathways and kinetics of degradation of deslorelin, pGlu1-His2-Trp3-Ser4-Tyr5-D-Trp6-Leu7-Arg8-ProNHEt9 (Des1-9), in a human airway epithelial cell line (Calu-1).. The degradation of deslorelin in membrane and cytosolic fractions of Calu-1 cells was studied at 37 degrees C up to 24 h. The degradation products were separated using HPLC and identified by amino acid analysis, sequencing, and mass spectrometry. The rate constants for deslorelin degradation and the formation of degradation products were determined by fitting the concentration vs. time data to pharmacokinetic models using WinNonlin. The effect of enzyme inhibitors, captopril, phosphoramidon, and disodium EDTA on deslorelin degradation was also assessed.. Des1-3, Des4-9, and Des5-9 were the deslorelin fragments detected in the membrane fraction. Apart from these degradation products. Des5-7 was also detected in the cytosolic fraction. The deslorelin degradation was 8.5 times faster in the cytosolic fraction compared to the membrane fraction. The disappearance of deslorelin and the kinetics of degradation products could be explained by simple 2 compartment iv bolus model and 1 compartment absorption model, respectively. EDTA and captopril decreased deslorelin degradation in the membrane and cytosolic fractions.. Deslorelin is initially cleaved at the 3-4 bond in the membrane and cytosolic fractions, possibly by a metalloendopeptidase and/or angiotensin converting enzyme, with the degradation being more rapid in the cytosol.

Topics: Cell Line, Tumor; Cytosol; Enzyme Inhibitors; Humans; Respiratory Mucosa; Signal Transduction; Triptorelin Pamoate

Three experiments were performed to test the following hypotheses: 1) stallions and/or progesterone-estradiol-treated geldings could serve as models for the effects of a single implant of the GnRH analog, deslorelin acetate, on LH and FSH secretion by mares; and 2) multiple implants of deslorelin acetate could be used as a means of inducing ovarian atrophy in mares for future study of the mechanisms involved in the atrophy observed in some mares after a single implant. In Exp. 1, nine light horse stallions received either a single deslorelin implant (n = 5) or a sham injection (n = 4) on d 0. In Exp. 2, 12 geldings received daily injections of progesterone on d -20 through -4, followed by twice-daily injections of estradiol on d -2 to 0. On the morning of d 0, geldings received either a single deslorelin implant (n = 6) or a sham injection (n = 6). Daily injections of progesterone were resumed on d 2 through 15. In Exp. 1, plasma LH and FSH were elevated (P < 0.05) in the treatment group relative to controls at 4, 8, and 12 h after implant insertion. In the treated stallions, FSH was decreased (P < 0.05) on d 3 to 13, and LH was decreased on d 6 to 13. In Exp. 2, plasma LH and FSH were elevated (P < 0.05) at 4,8, and 12 h after deslorelin implant insertion. Plasma LH was suppressed (P < 0.05) below controls on d 2 to 7, 9, and 11 to 15; plasma FSH was suppressed (P < 0.05) on d 4 to 15. In Exp. 3, 21 mares were used to determine whether multiple doses of deslorelin would cause ovarian atrophy. Mares received one of three treatments: 1) sham injections; 2) three implants on the first day; or 3) one implant per day for 3 d (n = 7 per group). Treatment with multiple implants increased (P < 0.05) the interovulatory interval by 14.8 d and suppressed (P < 0.01) LH and FSH concentrations for approximately 25 d; no mare exhibited ovarian atrophy. In conclusion, after an initial short-term increase in LH and FSH secretion, deslorelin implants caused long-term suppression of both gonadotropins in stallions as well as in geldings treated with progesterone and estradiol to mimic the estrous cycle. It is likely that either of these models may be useful for further study of this suppression in horses. Although multiple implants in mares suppressed gonadotropin secretion longer than a single implant, the lack of ovarian atrophy indicates that the atrophy observed after a single implant in previous experiments was likely due to the susceptibility of individual mares.

Topics: Animals; Dose-Response Relationship, Drug; Drug Implants; Enzyme Inhibitors; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Horses; Luteinizing Hormone; Male; Models, Animal; Ovary; Time Factors; Triptorelin Pamoate

We administered the aromatase inhibitor fadrozole to 16 girls with gonadotropin-independent precocious puberty due to the McCune-Albright syndrome. The girls' ages ranged from 3.2-9.7 yr, and their bone ages ranged from 5.75-14.25 yr. After baseline evaluations, fadrozole was started at a dose of 240 microg/kg.d (equivalent to the dose recommended for therapy of estrogen-dependent breast cancer) for 12-21 months and increased to 480 microg/kg.d for an additional 12 months in 10 girls. During treatment, seven girls had evidence of central precocious puberty; hence, the GnRH agonist deslorelin (4 microg/kg.d sc) was added to their regimen. One girl was on a long-acting GnRH agonist from the start of treatment. Patients were evaluated at 2-6-month intervals throughout treatment. After the first 6-12 months of treatment, fadrozole showed some benefits in 10 girls, including decrease in frequency of menses and/or rates of linear growth and bone maturation; however, fadrozole had no significant benefit in the group as a whole. The seven girls with evidence of central precocious puberty had no slowing in the progression of their puberty during the combined fadrozole and GnRH analog treatment. Adverse effects of fadrozole included inhibition of cortisol and aldosterone biosynthesis at the dose of 480 microg/kg.d, without clinical evidence of adrenal insufficiency. In addition, three patients complained of nonspecific abdominal pain during fadrozole treatment. In one patient, this resolved with a reduction in dose from 480 to 240 microg/kg.d; in two patients, it resolved spontaneously. One girl had muscle weakness and constipation on the 480 microg/kg.d. This resolved after discontinuation of the drug. We conclude that fadrozole is not sufficiently potent to block estrogen synthesis in most girls with gonadotropin-independent precocious puberty due to the McCune-Albright syndrome and may impair the adrenocortical stress response.

Topics: Age Determination by Skeleton; Aging; Aromatase Inhibitors; Child; Child, Preschool; Drug Therapy, Combination; Enzyme Inhibitors; Estradiol; Estrone; Fadrozole; Female; Fibrous Dysplasia, Polyostotic; Gonadotropin-Releasing Hormone; Growth; Humans; Menstruation; Ovary; Puberty, Precocious; Treatment Failure; Triptorelin Pamoate; Ultrasonography

In the present study, we tested the effect of treatment with a slow-release implant containing the gonadotrophin-releasing hormone agonist Deslorelin(TM) (Peptech Animal Health Australia, North Ryde, NSW, Australia) on pituitary and testicular function in mature male dogs. Four dogs were treated with Deslorelin (6-mg implant) and four were used as controls (blank implant). In control dogs, there were no significant changes over the 12 months of the study in plasma concentrations of luteinising hormone (LH) or testosterone, or in testicular volume, semen output or semen quality. In Deslorelin-treated dogs, plasma concentrations of LH and testosterone were undetectable after 21 and 27 days, testicular volume fell to 35% of pretreatment values after 14 weeks and no ejaculates could be obtained after 6 weeks. Concentrations returned to the detectable range for testosterone after 44 weeks and for LH after 51 weeks and both were within the normal range after 52 weeks. Semen characteristics had recovered completely by 60 weeks after implantation. At this time, the testes and prostate glands were similar histologically to those of control dogs. We conclude that a single slow-release implant containing 6 mg Deslorelin has potential as a long-term, reversible antifertility agent for male dogs.

Topics: Animals; Contraception; Contraceptive Agents, Male; Delayed-Action Preparations; Dogs; Drug Implants; Luteinizing Hormone; Male; Organ Size; Prostate; Semen; Testis; Testosterone; Triptorelin Pamoate

Following induction of ovulation with deslorelin acetate (Ovuplant), gonadotrophin concentrations are reduced in the subsequent cycle, leading to increased interovulatory intervals in some mares. This study determined whether implant removal after 2 days prevented the decrease in gonadotrophin concentrations and follicular growth during the ensuing cycle. Twenty-four mares were randomised equally into 3 groups. Group 1 ovulated spontaneously, Groups 2 and 3 received the deslorelin implant to induce ovulation. Two days after treatment, the implant was removed from Group 3. On Day 10 postovulation, FSH was lower (P = 0.009) in Group 2, but not different between Groups 1 and 3. Follicular diameter on Day 14 was less (P<0.05) in Group 2 (19.0 +/- 2.1 mm) than in Groups 1 and 3 (36.6 +/- 2.5 and 30.5 +/- 2.0 mm, respectively). Interovulatory interval was longer (P<0.05) for Group 2 (25.8 +/- 2.9 days) compared to Groups 1 and 3 (18.5 +/- 0.7 and 19.4 +/- 0.3 days, respectively). Removal of the deslorelin implant eliminated the decreased FSH secretion and the increased interovulatory interval associated with implant administration. Therefore, it is recommended that the implant be removed after ovulation is detected to prevent the occurrence of a prolonged interovulatory interval.

Topics: Animals; Drug Implants; Enzyme Inhibitors; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Gonadotropins; Horses; Ovarian Follicle; Ovulation; Ovulation Induction; Random Allocation; Time Factors; Triptorelin Pamoate

A tendency for deslorelin implants to suppress subsequent follicular growth and delay return to estrus following induced ovulation has been documented in nonlactating mares. To investigate this phenomenon in lactating mares, 22 broodmares in southeast Texas were administered either deslorelin or hCG to induce ovulation in the first postpartum estrus during February and March 2001. Mares were teased daily and examined twice weekly (Tuesdays and Thursdays) by transrectal ultrasonography. When a follicle >35 mm diameter was detected on Tuesday, mares were treated with either 2,500 U hCG administered intravenously or with one implant (2.1 mg) deslorelin administered subcutaneously. Mares were bred every other day until ovulation was detected or until they ceased behavioral estrus, and were examined 16 days after treatment to detect pregnancy. Follicular measurements were recorded for all mares during each examination, and interestrous intervals were recorded for mares not becoming pregnant. Treatment of mares with either hCG or deslorelin resulted in similar ovulatory responses and pregnancy rates. Deslorelin-treated mares had fewer ovarian follicles >20 mm in diameter 16 days after treatment than hCG-treated mares (P < 0.01). Interestrous intervals for mares failing to become pregnant on foal heat breeding were prolonged in deslorelin-treated compared to hCG-treated mares (P < 0.01). Date of treatment was negatively correlated with length of the interestrous interval in deslorelin-treated mares (P < 0.01), but was not correlated with length of interestrous interval in hCG-treated mares (P > 0.10). All mares failing to become pregnant from foal heat breedings became pregnant from later breedings, but the parturition to conception interval was prolonged in deslorelin-treated compared to hCG-treated mares that did not become pregnant on foal heat (P < 0.01).

Topics: Animals; Breeding; Chorionic Gonadotropin; Drug Implants; Estrus; Female; Gonadotropin-Releasing Hormone; Horses; Lactation; Ovarian Follicle; Ovulation Induction; Postpartum Period; Pregnancy; Reproduction; Seasons; Triptorelin Pamoate; Ultrasonography

Deslorelin implants, approved for use in inducing ovulation in mares, have been associated with prolonged interovulatory intervals in some mares. Administration of prostaglandins in the diestrous period, following a deslorelin-induced ovulation, has been reported to increase the incidence of delayed ovulations. The goals of the present study were: (1) to determine the percentage of mares given deslorelin that experience delayed ovulations with or without subsequent prostaglandin treatment, and (2) to determine if removal of the implant 48 h after administration would effect the interval to subsequent ovulation. We considered interovulatory intervals to be prolonged if they were greater than the mean +/- 2 standard deviation (S.D.) of the control group in study 1 and the hCG group in study 2. In study 1, we retrospectively reviewed reproduction records for 278 mares. We either allowed the mare to ovulate spontaneously or induced ovulation using deslorelin acetate implants or hCG. We administered prostaglandin intramuscularly, 5-9 days after ovulation in selected mares in each group. A higher percentage of mares which were induced to ovulate with deslorelin and given prostaglandins had a prolonged interovulatory interval (23.5%; n = 16), as compared to deslorelin-treated mares that did not receive prostaglandins (11.1%; n = 5). In study 2, we induced ovulation in mares with hCG (n = 47), a subcutaneous deslorelin implant via an implanting device provided by the manufacturer (n = 28), or a deslorelin implant via an incision in the neck (n = 43) and we removed the implant 48 h after administration. We administered prostaglandin to all mares 5-9 days after ovulation. In study 2, mares from which the implant was removed had a normal ovulation rate and none had a prolonged interval to ovulation. Administration of prostaglandin after deslorelin treatment was associated with a longer interval from luteolysis to ovulation than that found in mares not treated with deslorelin. Prostaglandin administration during diestrus may have exacerbated the increased interval to ovulation in deslorelin-treated mares. We hypothesize that prolonged secretion of deslorelin from the implant was responsible for the extended interovulatory intervals.

Topics: Animals; Chorionic Gonadotropin; Cloprostenol; Drug Implants; Female; Gonadotropin-Releasing Hormone; Horses; Humans; Ovulation; Ovulation Induction; Retrospective Studies; Time Factors; Triptorelin Pamoate

The GnRH analogue deslorelin, in long-acting biocompatible implants, was used as a contraceptive in 31 cheetahs (13 females and 18 males), 21 African wild dogs (15 females and 6 males), 10 lionesses and four leopards (three females and one male). A dose of 12 or 15 mg deslorelin was administered to lions, whereas 6 mg deslorelin was administered to the other species. Monitoring consisted of observations, measurement of plasma progesterone and testosterone concentrations, vaginal cytology and evaluation of semen and sex organs. Deslorelin induced contraception in lionesses for 12-18 months, and in female cheetahs and leopards for a minimum of 12 months after treatment. Two male cheetahs had no viable spermatozoa or detectable plasma testosterone 21 months after treatment with deslorelin. Female wild dogs responded less consistently and one bitch conceived 4 weeks after implantation. However, in nine bitches, mating could be postponed until the next breeding season. Male dogs responded consistently and the contraception was effective for approximately 12 months. Although lionesses and cheetahs may become attractive to males for a few days after treatment, mating was not observed. No side-effects or behavioural changes were noted, indicating that deslorelin is a safe drug to use for the contraception of the species described. Males remain fertile for the first 6 weeks after the insertion of implants and should be separated from cyclic females during this period.

Topics: Acinonyx; Africa, Southern; Animals; Animals, Zoo; Behavior, Animal; Carnivora; Contraception; Dogs; Drug Implants; Enzyme Inhibitors; Female; Follicle Stimulating Hormone; Lions; Luteinizing Hormone; Male; Progesterone; Sperm Count; Testosterone; Time Factors; Triptorelin Pamoate

The present experiment characterized the pituitary responsiveness to exogenous GnRH in the first 10 d after ovulation following commercially available deslorelin acetate implantation at the normal dosage for hastening ovulation in mares. Twelve mature, cyclic mares were assessed daily for estrus and three times weekly for ovarian activity starting May 1. Mares achieving a follicle at least 25 mm in diameter or showing signs of estrus were checked daily thereafter for ovarian characteristics. When a follicle >30 mm was detected, mares were administered either a single deslorelin acetate implant or a sham injection and then assessed daily for ovulation. On d 1, 4, 7, and 10 following ovulation, each mare was challenged i.v. with 50 microg GnRH, and blood samples were collected to characterize the LH and FSH responses. The size of the largest follicle on the day of treatment did not differ (P = 0.89) between groups. The number of days from treatment to ovulation was shorter (P < 0.001) by 2.0 d for the treated mares indicating a hastening of ovulation. The size of the largest follicle present on the days of GnRH challenge was larger in the treated mares on d 1 (P = 0.007) but smaller on d 10 (P = 0.02). In addition, the interovulatory interval was longer (P = 0.036) in the treated mares relative to controls by 4.4 d. Concentrations of FSH in plasma of the treated mares were lower (P < 0.05) than control concentrations from d 3 to 12; LH concentrations in the treated mares were lower (P < 0.05) relative to controls on d 0 to 5, d 7, and again on d 20 to 23. Progesterone values were the same (P = 0.99) for both groups from 2 d before ovulation though d 23. There was an interaction of treatment, day, and time of sampling (P < 0.001) for LH and FSH concentrations after injection of GnRH. Both the LH and FSH responses were suppressed (P < 0.009) in the treated mares relative to controls on d 1, 4, and 7; by d 10, the responses of the two groups were equivalent. In conclusion, deslorelin administration in this manner increased the interovulatory interval, consistently suppressed plasma LH and FSH concentrations, and resulted in a complete lack of responsiveness of LH and FSH to GnRH stimulation at the dose used during the first 7 d after the induced ovulation. Together, these results are consistent with a temporary down-regulation of the pituitary gland in response to deslorelin administered in this manner.

Topics: Animals; Drug Implants; Enzyme Inhibitors; Estrus; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Horses; Injections, Intravenous; Luteinizing Hormone; Ovulation Induction; Pituitary Gland; Time Factors; Triptorelin Pamoate

The ability of gonadotrophin releasing hormone (GnRH) agonist implants to suppress ovarian activity and prevent pregnancies, long-term, was examined in heifers and cows maintained under extensive management. At three cattle stations, heifers (2-year-old) and older cows (3- to 16-year-old) were assigned to a control group that received no treatment, or were treated with high-dose (12 mg, Station A) or low-dose (8 mg, Station B and Station C) GnRH agonist implants. The respective numbers of control and GnRH agonist-treated animals (heifers + cows) at each station were: Station A, 20 and 99; Station B, 19 and 89; Station C, 20 and 76. Animals were maintained with 4% bulls and monitored for pregnancy at 2-monthly intervals for approximately 12 months. Pregnancy rates for control heifers and control cows ranged from 60-90% and 80-100%, respectively, depending on the study site. The respective number of animals (heifers + cows) treated with GnRH agonist that conceived, and days to first conception, were: Station A, 9 (9%) and 336 +/- 3 days; Station B, 8 (10%) and 244 +/- 13 days; Station C, 20 (26%) and 231 +/- 3 days. Treatment with high-dose GnRH agonist prevented pregnancies for longer (approximately 300 days) than treatment with low-dose GnRH agonist (approximately 200 days). In the majority of heifers and cows treated with GnRH agonist, ovarian follicular growth was restricted to early antral follicles (2-4mm). The findings indicate that GnRH agonist implants have considerable potential as a practical technology to suppress ovarian activity and control reproduction in female cattle maintained in extensive rangelands environments. The technology also has broader applications in diverse cattle production systems.

Topics: Animal Husbandry; Animals; Australia; Body Weight; Cattle; Contraceptive Agents, Female; Drug Implants; Female; Fertility; Male; Ovarian Follicle; Pregnancy; Random Allocation; Seasons; Triptorelin Pamoate

The potential to use a GnRH agonist bioimplant and injection of exogenous LH to control the time of ovulation in a multiple ovulation and embryo transfer (MOET) protocol was examined in buffalo. Mixed-parity buffalo (Bubalus bubalis; 4-15-year-old; 529 +/- 13 kg LW) were randomly assigned to one of five groups (n = 6): Group 1, conventional MOET protocol; Group 2, conventional MOET with 12 h delay in injection of PGF2alpha; Group 3, implanted with GnRH agonist to block the preovulatory surge release of LH; Group 4, implanted with GnRH agonist and injected with exogenous LH (Lutropin, 25 mg) 24 h after 4 days of superstimulation with FSH; Group 5, implanted with GnRH agonist and injected with LH 36 h after superstimulation with FSH. Ovarian follicular growth in all buffaloes was stimulated by treatment with FSH (Folltropin-V, 200 mg) administered over 4 days, and was monitored by ovarian ultrasonography. At the time of estrus, the number of follicles >8 mm was greater (P < 0.05) for buffaloes in Group 2 (12.8) than for buffaloes in Groups 1(8.5), 3 (7.3), 4 (6.1) and 5 (6.8), which did not differ. All buffaloes were mated by Al after spontaneous (Groups 1-3) or induced (Groups 4 and 5) ovulation. The respective number of buffalo that ovulated, number of corpora lutea, ovulation rate (%), and embryos + oocytes recovered were: Group 1 (2, 1.8 +/- 1.6, 18.0 +/- 13.6, 0.2 +/- 0.2); Group 2 (4,6.1 +/- 2.9, 40.5 +/- 17.5, 3.7 +/- 2.1); Group 3 (0, 0, 0, 0); Group4 (6, 4.3 +/- 1.2, 69.3 +/- 14.2, 2.0 +/- 0.9); and Group 5 (1, 2.5 +/- 2.5, 15.5 +/- 15.5, 2.1 +/- 2.1). All buffaloes in Group 4 ovulated after injection of LH and had a relatively high ovulation rate (69%) and embryo recovery (46%). It has been shown that the GnRH agonist-LH protocol can be used to improve the efficiency of MOET in buffalo.

Topics: Animals; Buffaloes; Drug Implants; Female; Follicle Stimulating Hormone; Insemination, Artificial; Luteinizing Hormone; Ovarian Follicle; Ovary; Ovulation; Ovulation Induction; Triptorelin Pamoate; Ultrasonography

The requirement for pulsatile LH and the LH surge for the acquisition of oocyte fertilizing potential and embryo developmental competency was examined in Zebu heifers. Follicular growth was superstimulated using the GnRH agonist-LH protocol in which pulsatile LH and the preovulatory LH surge are blocked. In experiment 1, heifers were assigned on Day 7 of the estrous cycle to receive: group 1A (n = 5), 1.5 mg norgestomet (NOR) implant; group 1B (n = 5), GnRH agonist implant. Follicular growth was superstimulated with 2x daily injections of FSH from Day 10 (a.m.) to Day 13 (p.m.), with PGF2alpha injection on Day 12 (a.m.). Heifers were ovariectomized on Day 15 (a.m.) and oocytes were placed immediately into fertilization, without 24 h maturation. Respective cleavage and blastocyst development rates were: group 1A, 0/64 oocytes (0%) and 0/64 (0%); group 1B, 34/70 oocytes (48.6%) and 2/70 (2.9%). In experiment 2, heifers were assigned on Day 7 of the estrous cycle to receive: group 2A (n = 10), 1.5 mg NOR implant; group 2B (n = 10), GnRH agonist implant; group 2C (n = 10), GnRH agonist implant. Follicular growth was superstimulated as in experiment 1 above. Heifers in groups 2A and 2B received an injection of 25 mg LH on Day 14 (p.m.) and all heifers were ovariectomized on Day 15 (a.m.); oocytes were placed immediately into fertilization without 24 h maturation. Cleavage rates were similar for heifers in group 2A (84/175 oocytes, 48.0%), group 2B (61/112 oocytes, 54.5%) and group 2C (69/163, 42.3%). Blastocyst development rates were similar for heifers in group 2A (22/175 oocytes, 12.6%) and group 2B (25/112 oocytes, 22.3%) and lower (P < 0.05) for heifers in group 2C (9/163 oocytes, 5.5%). Oocytes obtained from heifers treated with GnRH agonist, without injection of exogenous LH, underwent cleavage indicating that neither pulsatile LH nor the preovulatory LH surge are obligatory for nuclear maturation in cattle oocytes. Exposure to a surge-like increase in plasma LH increased embryo developmental competency indicating that the preovulatory LH surge promotes cytoplasmic maturation. The findings have important implications for controlling the in vivo maturation of oocytes before in vitro procedures including nuclear transfer.

Topics: Animals; Blastocyst; Cattle; Cleavage Stage, Ovum; Drug Implants; Embryo, Mammalian; Female; Fertilization in Vitro; Follicular Phase; Luteinizing Hormone; Ovarian Follicle; Ovariectomy; Periodicity; Pregnenediones; Triptorelin Pamoate

The objective of this study was to compare the effectiveness of intramuscular sustained release Pluronic F127 (PF127) gel formulations of deslorelin, a potent GnRH agonist, and GnRH to their solution formulations in inducing the release of luteinizing hormone and formation of luteal tissue in cattle. Injectable gel formulations of deslorelin and GnRH were prepared using Pluronic F127 (25%, w/w), a block copolymer. PF127 gels sustained the in vitro release of deslorelin as well as GnRH at similar rates and reduced drug degradation in muscle tissue when compared to the solution formulations. Deslorelin, as well as GnRH, elicited desirable elevations in plasma LH and progesterone concentrations in vivo. When compared to the solution formulations, the gel formulations of both drugs induced a broader peak of LH. Also, the peak LH levels were lower and the peak times were delayed with the gel formulations compared to the solution formulations. While the solution dosage form of deslorelin and GnRH elicited similar responses, the PF127 gel formulation of deslorelin induced peak LH levels at an earlier time (3 h for deslorelin versus 5.25 h for GnRH). The results indicate that, deslorelin exerts a pharmacological effect in cattle. The LH response to deslorelin as well as GnRH can be altered by controlling the input or the release rate of the drug. PF127 gel formulations can sustain peptide release and reduce peptide degradation.

Topics: Animals; Cattle; Chemistry, Pharmaceutical; Delayed-Action Preparations; Gels; Gonadotropin-Releasing Hormone; Poloxamer; Triptorelin Pamoate

An experiment was conducted to investigate the potential of chronic delivery of a potent GnRH agonist (deslorelin) via subcutaneous implants to delay the resumption of ovulatory cycles in postpartum dairy cattle. Cows received either a single deslorelin implant (n=40; DES) within 7 days of calving or were untreated (n=24; CON). Blood samples were collected thrice weekly during the period the implants were in place. Plasma concentrations of progesterone (P4) and 17beta-oestradiol (E2) were measured along with selected serum metabolites. Implants were removed after 28 days and cattle monitored daily for behavioral oestrus. Serial weekly blood samples were collected to detect the occurrence of ovulation. Cows were artificially inseminated as they were detected in oestrus from 30 days after implant removal. Pregnancy status was subsequently determined by manual palpation of uterine contents at strategic intervals. Insertion of implants induced ovulation in 3/40 cows as determined by a rise in progesterone 7 days later. Deslorelin implants delayed the onset of ovulatory cycles compared with untreated herdmates (mean 43.4+/-4.2 versus 57.3+/-1.6 days postpartum; P<0.001). A noticeable delay of at least 12 days was observed between implant removal and the first animals ovulating. Mean plasma E2 concentrations during the period the implants were in place were similar for DES and CON cows that experienced a prolonged spontaneous postpartum anoestrus (low P4 >60 days), although both groups had concentrations only 20% of CON cows that had ovulated prior to 30 days postpartum. The patterns of recovery following implant removal were highly variable. A number of DES cows showed a low and transient rise in plasma progesterone around 21 days after implant removal. Some cows displayed oestrus but did not appear to form a fully functional corpus luteum with this phenomenon being more prevalent among DES cows (7 of 37 versus 1 of 21; P<0.05). Overall, significantly more DES cows were detected in oestrus without ovulating compared to CON cows. Final pregnancy rates did not differ between DES and CON groups. The mean time to conception for DES cows was longer (21.2+/-5.6 versus 41.1+/-7.4 days, CON versus DES; P<0.01). This difference was not present if the time from first ovulation to conception was compared (50.5+/-5.3 versus 43.5+/-9.3 days, CON versus DES; P>0.05). Deslorelin implants provided a reliable method of inducing anoestrus when treatment was initiated prior to 3

Topics: Animals; Cattle; Drug Implants; Estradiol; Female; Gonadotropin-Releasing Hormone; Ovulation Induction; Postpartum Period; Progesterone; Reproduction; Triptorelin Pamoate

The objective of the experiment was to investigate the potential for using a single injection of the GnRH agonist [D-Trp(6), Pro(9)-des-Gly(10)-NH(2)] GnRH-ethylamide (deslorelin) to suppress LH secretion in ovariectomised Holstein cows. Each dose of 10, 100 and 1000 microg deslorelin was injected intravenously into each of four ovariectomised cows on day 0. Blood samples were collected hourly on day 0 to profile the induced LH release. Frequent serial blood samples were collected at 10min intervals over 4h on days -3, -1, +2, +4 and +6. The injection of deslorelin induced a surge-like release of LH that begun within 1h in all cows. There was no difference between deslorelin doses in terms of maximum LH concentration, area under the LH curve (AUC) or log(10)(AUC). The average interval from injection to maximum LH concentration was longer for cows receiving 1000 microg than in those receiving 10 microg (3.5 versus 1.5h; P<0.01), though no different to 100 microg (2.8h; P>0.1). This relationship was described by a logarithmic function of deslorelin dose in micrograms (R(2)=73.3%, P<0.01). Pre-treatment smoothed mean LH concentration was significantly correlated with peak LH concentration of the induced surge: max_LH=5.37+9.57 x pre-amplitude (R(2)=33.2%, P=0.05). Similarly, LH pulse amplitude pre-deslorelin was also correlated with peak LH of the induced surge max_LH=0.07+12.9 x pre-amplitude (R(2)=53.7%, P=0.07). Pulsatile release of LH was suppressed only with the 1000 microg dose on day +2. Suppression was characterised by a reduction in mean LH, smoothed mean LH and LH pulse amplitude. By day +4, LH parameters were no different to pre-treatment ones. Pulse frequency was not affected by the treatment, although a small non-significant reduction at day +2 for 1000 microg dose was observed (3.9 versus 2.8, P=0.14). In conclusion, temporary suppression of LH output for at least 48h occurred following a single intravenous injection of 1000 microg of deslorelin, even though there were similar peak LH concentrations were for the three doses.

Topics: Animals; Cattle; Female; Gonadotropin-Releasing Hormone; Injections, Intravenous; Kinetics; Luteinizing Hormone; Ovariectomy; Periodicity; Triptorelin Pamoate

The objectives of the study were firstly to identify the role of the ovary in maintaining plasma luteinising hormone (LH) concentrations in cows treated with an implant of a potent GnRH agonist (deslorelin), and secondly to characterise the changes in LH following ovariectomy (OVX) in the same animals. Oestrus was synchronised in mature Holstein dairy cows and deslorelin implants were inserted 17 days later into two-third of the cows. A further 10 days later (day 0) all cows had bilateral OVX performed. A control group (CON; n=4) received no treatment and had blood samples collected at 15-min intervals for 8h on the day prior to OVX (day -1) and similarly on days 4 and 10. One group (DES_IN; n=4) had implants in place for the duration of the study while another group had implants removed (DES_OUT; n=4) at the time of OVX. DES_IN cows were sampled hourly at each sampling session (days -1, +4 and +10), whereas DES_OUT cows were sampled similarly to CON except on day -1 when hourly samples were collected. Predictable post-operative increases in mean LH (0.61 ng/ml versus 1.79 ng/ml; P<0.01) and LH pulse amplitude (0.66 ng/ml versus 1.56 ng/ml; day -1 versus day +10; P<0.01) occurred after CON cows were ovariectomised. Smoothed LH means showed a delayed effect of time compared to arithmetic means. Pulse frequency was unchanged following OVX in CON cows. A comparison of all cows that had been treated with deslorelin from day -1 showed a significant elevation of smoothed mean LH compared to untreated cows (0.80 ng/ml versus 0.34 ng/ml; DES_IN and DES_OUT versus CON; P<0.05). DES_IN cows had a 54% reduction in mean LH from day -1 to +4 following OVX (1.05 ng/ml versus 0.48 ng/ml; P<0.01) indicating the probable involvement of the ovary in the maintenance of elevated basal LH. No further reduction was detected by day +10. The LH response to an intramuscular (IM) injection of 500 microg 17beta-oestradiol (E2) on day +11 varied significantly between treatment groups (P<0.01). CON cows showed a typical LH surge, reaching maximum concentrations (10.3 ng/ml) at 17.3h post-injection. Even though low amplitude LH pulsatility had been restored in DES_OUT cows by day +4, there was an inconsistent response to E2 on day +12; one cow had an apparently normal surge yet, others showed only attenuated responses. Pulse amplitude in DES_OUT cows was lower at days +4 and +10 compared to CON (P<0.05). DES_IN cows did not produce any surge after E2. Mean LH prior to OVX (day -1) rem

Topics: Animals; Cattle; Drug Implants; Estradiol; Estrus Synchronization; Female; Gonadotropin-Releasing Hormone; Kinetics; Luteinizing Hormone; Ovariectomy; Periodicity; Software; Triptorelin Pamoate

The aim of this study was to evaluate the effect of delaying ovulation subsequent to superstimulation of follicular growth in beef cows (Bos indicus) on embryo recovery rates and the capacity of embryos to establish pregnancies. Ovulation was delayed by three treatments using either progesterone (CIDR-B) or a GnRH agonist (deslorelin). Multiparous Nelore cows (n = 24) received three of four superstimulation treatments in an incomplete block design (n = 18 per group). Cows in Groups CTRL, P48 and P60 were treated with a CIDR-B device plus estradiol benzoate (EB, 4 mg, i.m.) on Day-5, while cows in Group D60 were implanted with deslorelin on Day-7. Cows were superstimulated with FSH (Folltropin-V, 200 mg), from Day 0 to 3, using twice daily injections in decreasing amounts. All cows were treated with a luteolytic dose of prostaglandin on Day 2 (08:00 h). CIDR-B devices were removed as follows: Group CTRL, Day 2 (20:00 h); Group P48, Day 4 (08:00 h); Group P60, Day 4 (20:00 h). Cows in Group CTRL were inseminated at 10, 20 and 30 h after first detected estrus. Ovulation was induced for cows in Group P48 (Day 4, 08:00 h) and Groups P60 and D60 (Day 4, 20:00 h) by injection of LH (Lutropin, 25 mg, i.m.), and these cows were inseminated 10 and 20 h after treatment with LH. Embryos were recovered on Days 11 or 12, graded and transferred to synchronized recipients. Pregnancies were determined by ultrasonography around Day 100. Data were analyzed by mixed procedure, Kruskal-Wallis and Chi-square tests. The number of ova/embryos, transferable embryos (mean +/- SEM) and pregnancy rates (%) were as follows, respectively: Group CTRL (10.8+/-1.8, 6.1+/-1.3, 51.5), P48 (12.6+/-1.9, 7.1+/-1.0, 52.3), P60 (10.5+/-1.6, 5.7+/-1.3, 40.0) and D60 (10.3+/-1.7, 5.0+/-1.2, 50.0). There were no significant differences among the groups (P > 0.05). It was concluded that fixed time AI in association with induced ovulation did not influence embryo recovery. Furthermore, pregnancy rates in embryos recovered from cows with delayed ovulation were similar to those in embryos obtained from cows treated with a conventional superstimulation protocol.

Topics: Animals; Cattle; Embryo Transfer; Embryo, Mammalian; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Insemination, Artificial; Luteinizing Hormone; Ovarian Follicle; Ovary; Ovulation; Ovulation Induction; Pregnancy; Pregnancy Tests; Progesterone; Superovulation; Tissue and Organ Harvesting; Triptorelin Pamoate; Ultrasonography

The aim of these studies was to determine the effect of levels of dry matter (DM) and metabolisable energy (ME) intakes on clearance rate of progesterone (P4) in dairy cows. Thirty-two lactating Holstein-Friesian cows were selected for the study and were fed indoors in individual stalls for a period of 5 weeks. They were individually offered a diet of combinations of pasture, hay and pelleted cereal grain to achieve two different levels of DM and ME. In the first trial, 16 cows were allocated to two groups: (i) high DM (HDM), and (ii) low DM (LDM) intakes, while the amount of ME intake was constant. In the second trial, 16 cows were allocated to two groups: (i) high ME, and (ii) low ME intakes with similar amount of DM intake. A GnRH-agonist (deslorelin) was initially implanted in the ear of each cow to block endogenous P4 secretion. Then 3 weeks later, a CIDR device was inserted into the vagina of each cow and left in place for 11 days. Chromic oxide (Cr(2)O(3)) capsules were administered to allow daily faecal output (FO) to be estimated. Daily blood, faecal and milk samples were taken during the period of the experiment for P4 and faecal P4 metabolites analyses. Trial 1: The average milk yield was similar among cows in high and LDM intake groups (26.7 versus 25.0 l per day, P = 0.2). The average daily FO was 7.8 kg DM in the HDM and 5.7 in the LDM cows (P < 0.0001). Average daily DM intakes were 17.3 kg and 15.4 kg in the HDM and LDM groups, respectively (P < 0.0001). The average plasma P4 concentrations were similar between the two groups (1.56 versus 1.60 ng/ml, P = 0.7) but milk P4 concentrations were higher in LDM cows (4.6 versus 3.6 ng/ml, P = 0.02). The average daily excretion rate of P4 into the milk was higher in LDM cows (122.3 versus 88.5 microg, P = 0.002). The concentrations of faecal P4 metabolites (FP4M) were not influenced by the level of daily DM intake (2.85 versus 2.90 microg/g, P = 0.6). The average daily yields of FP4M were higher among cows in the HDM group (23.2 versus 16.3mg, P = 0.01). Trial 2: The average milk yield was 31.2l per day in HME cows compared to 25.0l per day in LME cows (P < 0.0001). The average daily FO was 7.8 kg DM in LME and 5.8 kg DM in HME cows (P < 0.0001), and the average DM content of faeces was higher in LME cows (15.8 versus 12.7%, P = 0.01). The average daily ME intake was 213MJ per day in HME group compared to 183MJ per day in LME group (P<0.0001). The average plasma and milk P4 concentrations were sim

Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Cattle; Eating; Energy Intake; Enzyme Inhibitors; Feces; Female; Gonadotropin-Releasing Hormone; Lactation; Metabolic Clearance Rate; Milk; Progesterone; Random Allocation; Triptorelin Pamoate

In some mares with lesions of the reproductive tract, embryo collection and survival rates are low, or collection of embryos is not feasible. For these mares, oocyte transfer has been proposed as a method to induce pregnancies. In this report, a method for oocyte transfer in mares and results of oocyte transfer performed over 2 breeding seasons, using mares with long histories of subfertility and various reproductive lesions, are described. Human chorionic gonadotropin or an implant containing a gonadotropin-releasing hormone analog was used to initiate follicular and oocyte maturation. Oocytes were collected by means of transvaginal ultrasound-guided follicular aspiration. Following follicular aspiration, cumulus oocyte complexes were evaluated for cumulus expansion and signs of atresia; immature oocytes were cultured in vitro to allow maturation. The recipient's ovary and uterine tube (oviduct) were exposed through a flank laparotomy with the horse standing, and the oocyte was slowly deposited within the oviduct. Oocyte transfer was attempted in 38 mares between 9 and 30 years old during 2 successive breeding seasons. All mares had a history of reproductive failure while in breeding and embryo transfer programs. Twenty pregnancies were induced. Fourteen of the pregnant mares delivered live foals. Results suggest that oocyte transfer can be a successful method for inducing pregnancy in subfertile mares in a commercial setting.

Topics: Animals; Chorionic Gonadotropin; Enzyme Inhibitors; Estrus; Female; Gonadotropin-Releasing Hormone; Horses; Insemination, Artificial; Laparoscopy; Male; Oocyte Donation; Pregnancy; Pregnancy Outcome; Reproduction; Triptorelin Pamoate

Prevention of high plasma progesterone concentrations in the early postpartum period may improve fertility. Our objective was to determine whether a Deslorelin implant (DESL; 2100 microg, s.c.) would reduce secretion of LH and alter follicle dynamics, plasma concentrations of progesterone, estradiol and PGF2alpha metabolite (PGFM) in postpartum dairy cows. Cows received DESL on Day 7 postpartum (Day 7, n=8) or were untreated (Control, n=9). All cows were injected with GnRH (100 microg, i.m.) on Day 14 to assess LH response. A protocol for synchronization of ovulation with timed AI was initiated on Day 60 (GnRH [Day 60], CIDR [Day 60 to Day 67], PGF2alpha [Day 67, 25 mg and Day 68, 15 mg], GnRH [Day 69] , AI [Day 70]). The LH response to injection of GnRH on Day 14 was blocked in animals treated with DESL. Numbers of Class 1 (<6 mm) follicles were unaffected (P > 0.05) whereas numbers of Class 2 (6 to 9 mm) (P < 0.01) and Class 3 (>9 mm) follicles were less (P < 0.01) in DESL cows between Day 7 and Day 21. From Day 22 to Day 60, DESL-treated cows had more of Class 1 follicles and less Class 2 (P < 0.01) and Class 3 (P < 0.01) follicles, and lower plasma concentrations of progesterone and estradiol (P < 0.01). Concentrations of PGFM between Day 7 and Day 42 were not affected by treatment (P > 0.05). All cows ovulated in response to GnRH on Day 69. Subsequent luteal phase increases in plasma progesterone concentrations (Day 70 to Day 84) did not differ. The use of the DESL implant associated with PGF2alpha given 14 days later suppressed ovarian activity and caused plasma progesterone concentrations to remain < 1 ng/mL between Day 22 and Day 51. The DESL implant did not affect milk production.

Topics: Animals; Cattle; Dinoprost; Drug Implants; Enzyme Inhibitors; Estradiol; Female; Gonadotropin-Releasing Hormone; Insemination, Artificial; Lactation; Linear Models; Luteinizing Hormone; Male; Milk; Ovary; Ovulation; Postpartum Period; Pregnancy; Progesterone; Random Allocation; Triptorelin Pamoate; Ultrasonography

We report 98 children who have reached final adult height in a long-term trial of LHRH agonist treatment. These children were 5.3 +/- 2.1 yr old at the start of treatment and were treated with either deslorelin (4 microg/kg.d sc) or histrelin (4-10 microg/kg.d) for an average of 6.1 +/- 2.5 yr. Final height averaged 159.8 +/- 7.6 cm in the 80 girls, which was significantly greater than pretreatment predicted height (149.3 +/- 9.6 cm) but still significantly less than midparental height (MPH) (163.7 +/- 5.6). Final height averaged 171.1 +/- 8.7 cm in the 18 boys, which was significantly greater than pretreatment predicted height (156.1 +/- 14.2 cm) but still significantly less than MPH (178.3 +/- 5.2 cm). However, the average adult height of the 54 children who had less than a 2-yr delay in the onset of treatment was not significantly different from their MPH, and 21 children exceeded MPH. Final height SD score correlated positively with duration of treatment (P < 0.01), midparental height (P < 0.001), predicted height at the start of treatment (P < 0.001), and growth velocity during the last year of treatment (P < 0.001) and correlated inversely with delay in the onset of treatment (P < 0.001), age at the start of treatment (P < 0.001), bone age at the start of treatment (P < 0.001), bone age at the end of treatment (P < 0.001), breast stage at the start of treatment (P = 0.02), and bone age minus chronological age at the start of treatment (P = 0.001). We conclude that LHRH agonist treatment improves the final height for children with rapidly progressing precocious puberty treated before the age of 8 yr for girls or 9 yr for boys. Less delay in the onset of treatment, longer duration of treatment, and lower chronological and bone age at the onset of treatment all lead to greater final height. All children with onset of pubertal symptoms before age 8 in girls and age 9 in boys should be evaluated for possible treatment. Treatment is appropriate in children with rapidly progressing puberty, accelerated bone maturation, and compromise of adult height prediction, regardless of bone age or chronological age at time of evaluation. However, once treatment is considered appropriate, it should be initiated quickly, because longer delays lead to shorter final height. In addition, the longer the treatment is continued, the greater is the final height outcome.

Topics: Age Factors; Body Height; Child; Child, Preschool; Female; Gonadotropin-Releasing Hormone; Humans; Infant; Male; Puberty, Precocious; Triptorelin Pamoate

To evaluate the potential of an implant of a GnRH-agonist (deslorelin) to create a progesterone free animal suitable for studying progesterone (P4) metabolism in intact cows by measuring blood P4 and faecal P4 metabolites.. Experiment 1: Eighteen non-lactating cycling Holstein-Friesian cows, 4 to 7 years old, were allocated to one of three groups to study plasma P4 concentrations preceding an intravaginal insert. These groups comprised: i) a deslorelin group (GnRH-agonist implanted); ii) a PGF group receiving two injections of prostaglandin (PGF2alpha) 12 days apart; and, iii) an ovariectomised (OVX) group. An intravaginal device (CIDR) was inserted into the vagina of each animal and left in place for 11 days. Plasma P4 concentrations were measured during the study period. Experiment 2: Twelve non-lactating cycling Holstein-Friesian cows, 4 to 7 years old, were allocated to two groups: i) a deslorelin group (GnRH-agonist implanted); and ii) an ovariectomised group. Plasma P4 and faecal P4 metabolites (20-oxo-pregnanes, 20alpha-OH and 20beta-OH) were monitored for a period of 5 weeks.. Experiment 1: Average plasma P4 concentration did not differ between the three groups (1.28, 1.43 and 1.55 ng/mL for deslorelin, OVX and PGF cows, respectively, P = 0.8) during the period of supplementation. Experiment 2: There was no difference in plasma P4 (mean plasma P4 < 0.02 ng/mL, P = 0.9) and faecal P4 metabolites between deslorelin and OVX cows 2 weeks after the implantation (P = 0.7).. These data showed that a GnRH-agonist (deslorelin) implant may be used as an alternative to ovariectomy to create a progesterone free animal suitable for studying the metabolism of administered P4.

Topics: Administration, Intravaginal; Animals; Body Weight; Cattle; Drug Implants; Enzyme Inhibitors; Feces; Female; Gonadotropin-Releasing Hormone; Ovariectomy; Ovary; Pregnanes; Progesterone; Triptorelin Pamoate; Ultrasonography

The purpose of this study is to investigate the mechanisms and thermodynamics of the interaction between hydroxypropyl beta-cyclodextrin (HPdetaCD) and [D-Trp6, des-Gly10] LHRH ethylamide (deslorelin), a peptide drug.. We used UV and fluorescence spectroscopy to study the interaction of HPbetaCD and deslorelin. Circular dichroism was used to study the conformational changes induced in deslorelin upon interaction with HP beta CD. The thermodynamics of the interaction of deslorelin and HPbetaCD was studied using isothermal titration calorimetry (ITC). We also determined the effect of HPbetaCD on the degradation of deslorelin by alpha-chymotrypsin.. UV and fluorescence spectroscopy indicated that HPbetaD induced a change in polarity of the environment surrounding the chromophores of deslorelin. Wavelength selective fluorescence indicated an increase in the fluorescence polarization of deslorelin with an increase in excitation wavelength in the presence of HPbetaCD suggesting that tryptophan is present in a media of reduced mobility. Circular dichroism studies indicated that HPbetaCD stabilizes the conformation of deslorelin. In addition, ITC indicated an exothermic reaction between deslorelin and HPbetaCD with a low enthalpy of binding of approximately -600 cal/mol and a binding affinity of approximately -1.25 x 10(2) M-1. Finally, the rate of degradation of deslorelin by alpha-chymotrypsin was decreased by 33% in the presence of HPbetaCD.. These results indicate that there is an interaction between HPbetaCD and deslorelin, which involves the inclusion of aromatic amino acids of deslorelin into the hydrophobic cavity of the cyclodextrin. This inclusion, providing steric hindrance, may be one of the mechanisms by which HPbetaCD reduces enzymatic hydrolysis of deslorelin.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; alpha-Cyclodextrins; Amino Acids, Aromatic; beta-Cyclodextrins; Chymotrypsin; Cyclodextrins; Drug Interactions; Drug Stability; Excipients; Gonadotropin-Releasing Hormone; Protein Conformation; Spectrometry, Fluorescence; Thermodynamics; Triptorelin Pamoate

Studies were undertaken in Australia and Belgium to determine whether the initial pro-oestrous-oestrous responses of anoestrous bitches to treatment with deslorelin administered in a s.c. implant were inhibited by progestin treatment. Thirty-nine bitches of mixed breeding were treated daily with 2 mg megestrol acetate kg-1 body weight for 21 (group 1, n = 5) or 14 days (group 2, n = 10), or with 1 mg megestrol acetate kg-1 body weight for 14 days (group 3, n = 10). A deslorelin (6 mg) implant was placed s.c. on day 14 (group 1) or day 7 (groups 2 and 3) of treatment. Bitches not treated with progestin also received a deslorelin implant (group 4, n = 9) or were untreated controls (group 5, n = 9). Signs of pro-oestrus-oestrus were not observed in bitches in groups 1, 2 and 5, but were observed in bitches in groups 3 (4/10) and 4 (9/9). Four bitches in group 4 were mated, two of which became pregnant. The pregnancies failed at about day 40 of gestation and were associated with low plasma progesterone concentrations. Treatment with progestin inhibited the pro-oestrous-oestrous responses of bitches to deslorelin.

Topics: Animals; Contraceptive Agents; Depression, Chemical; Dogs; Drug Implants; Estradiol; Estrus; Female; Gonadotropin-Releasing Hormone; Megestrol Acetate; Pregnancy; Progesterone; Time Factors; Triptorelin Pamoate

The aim of this study was to develop a method for long-term but reversible inhibition of oestrous cycles in female cats by downregulation of GnRH receptors with deslorelin released from a long-acting implant. In a blind study with mature cats (n = 20), a 6 mg deslorelin implant was administered s.c. to ten cats and a placebo implant was administered to ten cats. Occurrence of oestrus and general health were observed daily, and individual faecal samples were collected at 3 day intervals for 14 months and analysed for oestradiol content. All the placebo-treated queens continued to undergo normal oestrous cycles during the study. Oestrus was accompanied by peaks in oestradiol concentrations of > or = 20 ng g-1 faeces. Treatment with deslorelin initially stimulated oestradiol release, which accompanied treatment-induced ovulations. Thereafter, oestradiol concentrations decreased to 1-10 ng g-1 faeces and remained low for extended periods. Observations of small increases in oestradiol concentrations in one cat led to a second treatment with 6 mg deslorelin in five cats on day 155 after first treatment. Faecal oestradiol concentrations remained < 20 ng g-1 faeces in the five single treatment cats for 8.0, 8.5, 11.0 and 14.0 (two cats) months. Cats receiving two implants had the first oestradiol peak > 20 ng g-1 faeces after treatment at 7.5, 11.0 (two cats), 11.5 and 14.0 months. After 14 months, two cats had returned to normal cyclic activity, two had irregular small oestrogen peaks and six showed no cyclic activity. For months 2-5, 6-10 and 11-14, oestrogen values in treated cats were significantly different from control values (P < 0.001, 0.05 and 0.02, respectively). Differences in oestrogen concentration between control cats and cats that were treated twice were significant (P < 0.001) during months 6-10 only. The general health of treated cats was unchanged throughout the study. These results confirm that deslorelin can effectively suppress ovarian activity in domestic cats, but that the duration of suppression varies among individuals.

Topics: Animals; Cats; Contraception; Contraceptive Agents; Depression, Chemical; Drug Implants; Estradiol; Estrus; Estrus Detection; Feces; Female; Gonadotropin-Releasing Hormone; Single-Blind Method; Time Factors; Triptorelin Pamoate

Continuous low-dose administration of a GnRH analogue postpones oestrus in bitches and suppresses reproductive function in dogs. A new drug delivery formulation that could enhance the practicality of this approach for the control of reproduction has been developed. The objective of the present study was to determine whether this method of delivery could, by sustained release of the GnRH analogue deslorelin, act as a reversible anti-fertility agent in domestic male and female dogs for periods exceeding 1 year. Several long-term studies were performed, which monitored reproductive function in 30 dogs and 52 bitches. Suppression of reproductive function in male dogs was dose-related. Spermatogenesis was suppressed for more than a year in 14 of 16 dogs that received doses of > 0.25 mg deslorelin kg-1. In females, postponement of oestrus for periods of up to 27 months was observed, but there was no relationship between the stage of the oestrous cycle at the start of treatment and the duration of efficacy. Treatment-induced effects on fertility were reversible in both sexes. In summary, sustained release deslorelin implants were shown to elicit reversible long-term reproductive control in male and female domestic dogs.

Topics: Animals; Contraception; Contraceptive Agents; Contraceptive Agents, Female; Contraceptive Agents, Male; Dogs; Dose-Response Relationship, Drug; Drug Implants; Estrus; Female; Gonadotropin-Releasing Hormone; Male; Spermatogenesis; Triptorelin Pamoate

The GnRH analogue deslorelin, in long-acting implants, was used in an attempt to temporarily control reproduction or aggression in wild carnivores in southern Africa and the USA. In the southern African study, 6 mg deslorelin was administered to cheetahs (eight females, four males), one female leopard and wild dogs (six females, one male) housed in groups, and 12 mg deslorelin was administered to two lionesses. None of the animals became pregnant after deslorelin administration apart from one wild dog that was mated at the initial treatment-induced oestrus. Two wild dogs and one lioness came into oestrus 12 and 18 months after deslorelin administration, respectively, thus demonstrating that the anti-fertility effects of deslorelin are reversible. Two lionesses and four cheetahs underwent oestrus without allowing mating 2-14 days after treatment. Simultaneous administration of progestins to three bitches and one lioness did not suppress oestrus. Male cheetahs had no spermatozoa on day 82 after treatment and did not impregnate two untreated females. Of three untreated female wild dogs housed with treated males, only the first female to enter oestrus (21 days after deslorelin administration) became pregnant. One month after treatment, plasma testosterone concentrations of male dogs were at basal values. In the USA study, three male sea otters that had been treated with 6 mg deslorelin ceased antagonistic behaviour and blood testosterone concentrations and size of the testes were still sharply reduced 24 months after treatment. Male red (n = 7) and grey (n = 5) wolves received 6 mg deslorelin in December 1998 but no effects on seasonal spermatogenesis and behaviour were observed. In a black-footed cat, sperm production, libido and aggressiveness decreased in response to treatment with 3 mg deslorelin and penile spines were not observed within 3 months after treatment, but were observed again 4-6 months later. Treatment of female red (n = 5) and grey (n = 5) wolves with deslorelin in December 1999 triggered preseason oestrus and mating, which were followed by one abortion and one successful pregnancy. Contraception was achieved in female Fennec foxes (n = 7) and two lionesses, which was observed in the foxes by an absence of increases in faecal progesterone concentrations. In two male bush dogs, administration of 3 mg deslorelin once or twice was insufficient to suppress reproductive function or behaviour.

Topics: Acinonyx; Animals; Animals, Wild; Carnivora; Contraception; Contraceptive Agents; Drug Implants; Estrus; Feces; Female; Foxes; Gonadotropin-Releasing Hormone; Lions; Male; Otters; Progesterone; Sexual Behavior, Animal; South Africa; Spermatogenesis; Testosterone; Triptorelin Pamoate; United States

Development of a controlled release formulation of gonadotropin releasing hormone that would stimulate a LH surge capable of reducing the time span of ovulations would greatly benefit reproductive management because a single timed insemination could be used. A dose-response study was conducted to determine if Deslorelin, a potent gonadotropin releasing hormone analogue, delivered via the SABER system, a biodegradable controlled release system, would stimulate an ovulatory-like LH surge in the pig. Twenty ovariectomized gilts, approximately 200 d old and 100 kg body weight (BW), received estradiol benzoate (15 microg/kg BW im) and 48 h later, the gilts were given deslorelin at 0, 12.5, 25.0, 50.0 or 100.0 microg im (n = 4 each treatment group). Compared to controls, mean blood deslorelin concentrations were still elevated at 30 h after deslorelin. Mean deslorelin magnitude, area under the curve and duration were sequentially greater (P<0.05) in a dose-dependent sequence. Compared to controls, serum LH concentrations were elevated (P<0.05) for 6 to 12 h after deslorelin. A dose-response relationship was absent for all parameters of LH secretion. Magnitude of the serum LH response was greatest (P<0.05) in the 12.5 microg and 50.0 microg groups, whereas area under the curve was lower (P<0.05) after 25.0 microg of deslorelin than after 12.5, 50.0 and 100.0 microg, which were not different from each other. Thus, no more than 12.5 microg of deslorelin is necessary to obtain maximum LH release in the model studied and doses less than 12.5 microg may also be effective.

Topics: Animals; Area Under Curve; Delayed-Action Preparations; Dose-Response Relationship, Drug; Enzyme Inhibitors; Estradiol; Estrus Synchronization; Female; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Ovariectomy; Radioimmunoassay; Swine; Triptorelin Pamoate

Although the GnRH agonist analogs have become an established treatment for precocious puberty, there have been few long term studies of reproductive function and general health after discontinuation of therapy. To this end, we compared peak LH and FSH after 100 microg sc GnRH, estradiol, mean ovarian volume (MOV), age of onset and frequency of menses, body mass (BMI), and incidence of neurological and psychiatric problems in 2 groups of girls: those with precocious puberty due to hypothalamic hamartoma (HH; n 18) and those with idiopathic precocious puberty (IPP; n = 32) who had been treated with deslorelin (4-8 microg/kg x day, s.c.) or histrelin (10 microg/kg x day, s.c.) for 3.1-10.3 yr and were observed at 1, 2, 3, and 4-5 yr after discontinuation of treatment. The endocrine findings were also compared to those in 14 normal perimenarcheal girls. There were no differences between the HH and IPP groups in age or bone age at the start of treatment, at the end of treatment, or during GnRH analog therapy. We found that whereas the peak LH level was higher in HH than in IPP girls before (165.5 +/- 129 vs. 97.5 +/- 55.7; P < 0.02) and at the end (6.8 +/- 6.0 vs. 3.9 +/- 1.8 mIU/mL; P < 0.05) of therapy, this difference did not persist at any of the posttherapy time points. LH, FSH, and estradiol rose into the pubertal range by 1 yr posttherapy in both HH and IPP. However, the mean posttherapy peak LH levels in both HH and IPP groups tended to be lower than normal, whereas the peak FSH levels were not different from normal, so that the overall posttherapy LH/FSH ratio was decreased compared to that in the normal girls (HH, 2.7 +/- 0.3; IPP, 2.6 +/- 0.1; normal, 5.2 +/- 4.8; P < 0.05). The MOV was larger in HH than IPP at the end of treatment (3.7 +/- 3.5 vs. 2.0 +/- 1.2 mL; P < 0.05) and tended to increase in both groups over time to become larger than that in normal girls by 4-5 yr posttherapy (HH, 14.9 +/- 12.9; IPP, 7.6 +/- 2.2; normal, 5.4 +/- 2.5 mL; P < 0.05). Whereas the onset of spontaneous menses varied widely in both groups, once menses had started, the HH group had a higher incidence of oligomenorrhea. Pelvic ultrasonography revealed more than 10-mm hypoechoic regions in 4 HH patients, 15 IPP patients, and 3 normal girls, all of whom were reporting regular menses. Live births of normal infants were reported by 2 HH and 2 IPP patients, and elective terminations of pregnancy were reported by 1 HH and 2 IPP patients. BMI was greater than normal in HH

Topics: Adolescent; Child; Child, Preschool; Estradiol; Female; Follicle Stimulating Hormone; Follow-Up Studies; Gonadotropin-Releasing Hormone; Hamartoma; Humans; Hypothalamic Diseases; Luteinizing Hormone; Pregnancy; Puberty, Precocious; Reproduction; Triptorelin Pamoate

Short term treatment with spironolactone, testolactone, and, after the onset of central puberty, deslorelin can normalize the rate of growth and bone maturation in boys with familial male-limited precocious puberty. To test the hypothesis that this treatment can achieve long term normalization of the growth and development of these children, we examined the growth rate, bone maturation rate (change in bone age/change in chronological age), and predicted adult height of 10 boys who were treated with spironolactone (5.7 mg/kg x day) and testolactone (40 mg/kg x day) for at least 6 yr. Deslorelin (4 microg/kg x day) treatment was initiated 2.6 +/- 1.3 yr after beginning spironolactone and testolactone treatment. The growth rate normalized within 1 yr of starting treatment and remained normal during the next 5 yr of treatment (P < 0.001). The rate of bone maturation normalized during the second year of treatment and remained normal thereafter (P < 0.001). Predicted height increased from 160.7 +/- 14.7 centimeters at baseline to 173.6 +/- 10.1 centimeters after 6 yr of treatment (P < 0.05 during the fourth through the sixth year of treatment compared to baseline). We conclude that long term treatment with spironolactone, testolactone, and, after central puberty, deslorelin normalizes the growth rate and bone maturation and improves the predicted height in boys with familial male-limited precocious puberty. The ultimate effect of this approach on adult height will require further study.

Topics: Adolescent; Bone Development; Child; Child, Preschool; Gonadotropin-Releasing Hormone; Growth; Humans; Male; Puberty, Precocious; Spironolactone; Testolactone; Testosterone; Triptorelin Pamoate

Investigations in different species including the horse have demonstrated that prostaglandin F2 alpha (PGF2 alpha) is involved in initiating uterine contractions occurring during mating and artificial insemination (A.I.). Uterine contractions play an important role with respect to the sperm transport within the female genital tract. The objective of the present investigation was to evaluate whether the administration of PGF2 alpha (Dinoprost) synchronously to A.I. could have a positive effect on the pregnancy rate in mares. A field study including 346 warmblood-mares (age two to 20 years) belonging to a private studfarm was conducted during the breeding season 1996. The mares were assigned to two groups, group A: mares with spontaneous ovulation, group B: mares in which the ovulation was induced by a GnRH-analog-implant (Deslorelin). PGF2 alpha (Dinoprost) was administered either intramusculary (i.m., 5.0 mg) or intrauterine (i.ut., 0.5 mg diluted in 1.9 ml isotonic NaCl-solution and added to the semen dosis). The study was carried out in a double-blind fashion using isotonic NaCl-solution as a placebo. The mares of each group were randomly assigned to one of the two treatments (i.m. vs. i.ut.). The following first cycle pregnancy rates (day 18) were obtained in mares treated and inseminated once per oestrus: group A1 (PGF2 alpha, i.m.): 54.5% (n = 33); group A2 (placebo, i.m.): 69.7% (n = 33); group A3 (PGF2 alpha, i.ut.): 65.4% (n = 26); group A4 (placebo, i.ut.): 69.8% (n = 32); group B1 (PGF2 alpha, i.m.): 56.5% (n = 46); group B2 (placebo, i.m.): 29.6% (n = 27); group B3 (PGF2 alpha, i.ut.): 66.7% (n = 45); group B4 (placebo, i.ut.): 60.0% (n = 30). The pregnancy rates did not differ between the different groups with the exception of group B2 (p < 0.05). In mares treated repeatedly during the oestrus period (group A, n = 88; group B, n = 23), the pregnancy rates did not differ significantly between treatment and control groups. From the results obtained it is concluded that the PGF2 alpha-application did not show an effect on the pregnancy rate. Further factors influencing the results to a small degree were the stallions, semen age and quality and frequency of insemination per oestrus.

Topics: Animals; Dinoprost; Drug Implants; Female; Fertilization; Gonadotropin-Releasing Hormone; Horses; Insemination, Artificial; Ovulation; Ovulation Induction; Pregnancy; Pregnancy, Animal; Triptorelin Pamoate

We have tested the hypothesis "that the ovulation rate in homozygous carriers (BB) and noncarriers (+2) of the Booroola FecB gene would not be different if the plasma concentrations of follicle-stimulating hormone (FSH) in the two genotypes were similar." For this purpose we used two experimental animal models: 1) the hypothalamic-pituitary disconnected (HPD) ovary-intact ewe; and 2) and GnRH agonist (i.e., Deslorelin)-treated ewe. Following HPD or Deslorelin treatment, the animals had low plasma concentrations of gonadotropins and were anovulatory. In both animal models, BB and +2 ewes were treated with exogenous pregnant mares serum gonadotropin (PMSG) and varying doses of FSH to induce preovulatory follicular growth, and human chorionic gonadotropin (hCG) to induce ovulation. HPD or Deslorelin-treated animals administered with pregnant mares serum gonadotropin without FSH followed by human chorionic gonadotropin failed to ovulate. However for both animal models, the proportion of BB and +2 ewes ovulating to various doses of FSH differed such that significantly greater proportions of +2 animals ovulated relative to the BB genotype (P < 0.05). When HPD or Deslorelin-treated BB and +2 ewes were administered identical doses of FSH, the mean ovulation rate and plasma concentrations of FSH in those animals which ovulated was the same in both genotypes. These findings confirm, at least in part, the aforementioned hypothesis. The results also demonstrated that higher ovulation rates were obtained in both genotypes as the FSH dose was increased. Collectively, these findings infer that the higher mean ovulation rate in normal intact BB ewes compared to the +2 genotype is attributable to effects of the FecB gene at the level of ovarian follicular development as well as at the level of pituitary FSH release.

Topics: Animals; Anovulation; Bacterial Proteins; Carrier Proteins; Chorionic Gonadotropin; Escherichia coli Proteins; Female; Follicle Stimulating Hormone; Genotype; Gonadotropin-Releasing Hormone; Homozygote; Hypothalamo-Hypophyseal System; Ion Pumps; Luteinizing Hormone; Ovulation; Pregnancy; Sheep; Triptorelin Pamoate

The stability of a luteinizing hormone-releasing hormone (LHRH) analog in rat serum was studied under reproduced experimental analysis conditions. Serum samples of deslorelin [D-Trp6, Des-Gly, NH2(10)] LHRH ethylamide were exposed to multiple freeze-thaw cycles to determine the maximum number of cycles the serum sample can be exposed to without producing any quantitative changes in radioimmunoassay (RIA) measurements of deslorelin. A significant cycle effect was observed after completion of the sixth cycle. Serum samples were also stored at standardized -50 degrees C conditions for variable periods of time to determine the effects of acute and chronic storage time on deslorelin stability. Matched-pair t-test analysis showed no significant changes in deslorelin values as measured by RIA for a 3-week, 4-month, or 2-year storage period. The conditions in which the rat serum samples were stored prior to analytical analysis were sufficient to prevent detectable degradation of the deslorelin peptide.

Topics: Animals; Blood Chemical Analysis; Drug Stability; Enzyme Inhibitors; Freezing; Gonadotropin-Releasing Hormone; Hot Temperature; Humans; Radioimmunoassay; Rats; Reproducibility of Results; Time Factors; Triptorelin Pamoate

Topics: Clinical Trials as Topic; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Male; Prostatic Neoplasms; Puberty, Precocious; Triptorelin Pamoate

It was the aim of this study to determine whether deslorelin is degraded by the rabbit corneal tissue and to further delineate the mechanisms. Deslorelin was incubated with intact cornea either alone or in the presence of 0.1 mM ouabain, 0.1% 2,4-dinitrophenol, 0.1 mM phosphoramidon, 0.1 mM N-tosyl-L-phenylalanine chloromethylketone (TPCK), 0.1-2% EDTA, 0.1-1% ZnCl2, 0.1% dithiothreitol (DTT), or 0.1% N-ethylmaleimide (NEM) at 37 degrees C. In addition, deslorelin alone was incubated with cornea at 4 degrees C. Following a 90-min incubation, the supernatants were analyzed using a reversed-phase HPLC. Metabolite peaks observed in controls at 37 degrees C were not detected in the low-temperature study, suggesting inhibition of metabolism at low temperature. Intact drug remaining in the supernatant was not altered by ouabain and dinitrophenol, suggesting that energy-dependent corneal uptake is not likely for deslorelin. Phosphoramidon and TPCK failed to alter deslorelin levels, indicating that phosphoramidon and TPCK-sensitive endopeptidases did not contribute to the observed metabolism. DTT and NEM also failed to affect deslorelin levels. However, 2% EDTA and 1% ZnCl2 significantly elevated the intact deslorelin levels by 44 and 60%, respectively, and the metabolite peaks almost completely disappeared. These observations are consistent with the corneal metabolism of deslorelin by either metallo-peptidases or metal-dependent peptidases.

Topics: 2,4-Dinitrophenol; Animals; Chlorides; Chromatography, High Pressure Liquid; Cornea; Dithiothreitol; Drug Stability; Edetic Acid; Ethylmaleimide; Female; Glycopeptides; In Vitro Techniques; Ouabain; Rabbits; Receptors, LHRH; Temperature; Tosylphenylalanyl Chloromethyl Ketone; Triptorelin Pamoate; Zinc Compounds

Testosterone secretion and the expression and relative contents of steroidogenic acute regulatory (StAR) protein and steroidogenic enzymes cholesterol side-chain cleavage cytochrome P450 (P450SCC), 3beta-hydroxysteroid dehydrogenase/delta(5)-->delta(4)-isomerase (3 beta-HSD), and (17)alpha-hydroxylase cytochrome P450/C17-20 lyase (P450(17)alpha) were determined in testicular tissues of bulls treated with a LHRH agonist. Testis morphology and spermatogenesis were also examined. In Experiment 1, bulls (30-mo-old) received no treatment (control, n = 7) or were implanted for 10 days with the LHRH agonist deslorelin (n = 7). Bulls were castrated on Day 10 and testis tissues prepared for Western and Northern blotting. At castration, bulls implanted with deslorelin had greater plasma testosterone (5-fold) and testis content of testosterone (10-fold) compared with control bulls. Relative content (per micrograms total testis protein or RNA) of StAR protein, 3beta-HSD, P450SCC, and mRNA for P450(17)alpha in bulls treated with deslorelin ranged from 3- to 6-fold that of control bulls. In Experiment 2, bulls (20-mo-old) were left untreated (control, n = 6) or implanted with deslorelin (n = 12) for 120 days. On Day 120, bulls were castrated and right testis tissues prepared for morphology. Testis volume and weight were increased (P < 0.01) in bulls treated with deslorelin compared with control bulls. Stereological analysis revealed that this increase occurred in all compartments (seminiferous epithelium, lumen and interstitium) studied, but was significant (P < 0.01) only for the seminiferous epithelium. Absolute numbers of round spermatids per testis were increased (P < 0.05) in bulls treated with deslorelin compared with control bulls. Increased testosterone secretion in bulls treated with deslorelin was associated with increased testicular StAR protein and steroidogenic enzymes. Bulls treated long-term with deslorelin had a faster rate of testis growth and increased daily sperm production at the end of the experiment.

Topics: 17-Hydroxysteroid Dehydrogenases; Alcohol Dehydrogenase; Animals; Blotting, Northern; Blotting, Western; Cattle; Cholesterol Side-Chain Cleavage Enzyme; Drug Implants; Enzyme Inhibitors; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Male; Peptidylprolyl Isomerase; Phosphoproteins; Random Allocation; RNA, Messenger; Seminiferous Epithelium; Seminiferous Tubules; Spermatids; Spermatogenesis; Steroid 17-alpha-Hydroxylase; Testis; Testosterone; Triptorelin Pamoate

Information on the number of motile spermatozoa needed to maximize pregnancy rates for frozen-thawed stallion semen is limited. Furthermore, concentration of spermatozoa per 0.5-mL straw has been shown to affect post-thaw motility (7). The objectives of this study were 1) to compare the effect of increasing the concentration of spermatozoa in 0.5-mL straws from 400 to 1,600 x 10(6) spermatozoa/mL on pregnancy rate of mares, and 2) to determine whether increasing the insemination dose from approximately 320 to 800 million progressively motile spermatozoa after thawing would increase pregnancy rates. Several ejaculates from each of 5 stallions were frozen in a skim milk-egg yolk based freezing medium at 2 spermatozoal concentrations in 0.5-mL polyvinyl-chloride straws. Half of each ejaculate was frozen at 400 x 10(6) cells/mL and half at 1,600 x 10(6) cells/mL. Insemination doses were based on post-thaw spermatozoal motility and contained approximately 320 x 10(6) (320 to 400) motile spermatozoa or approximately 800 x 10(6) (800 to 900) motile spermatozoa. Sixty-three mares were assigned to 1 of 4 spermatozoal treatments (1--low spermatozoal number, low concentration; 2--low spermatozoal number, high concentration; 3--high spermatozoal number, low concentration; 4--high spermatozoal number, high concentration) and were inseminated daily. Post-thaw spermatozoal motility was similar for cells frozen at both spermatozoal concentrations (P > 0.1). One-cycle pregnancy rates were 15, 40, 28 and 33%, respectively, for Treatments 1, 2, 3 and 4. Packaging spermatozoa at the high concentration tended to increase pregnancy rates vs packaging at the low concentration (37 vs 22%; P = 0.095). Furthermore, when the lower spermatozoal number was used, there tended (P < 0.1) to be a higher pregnancy rate if spermatozoa were packaged at the higher concentration. There was no increase in pregnancy rates when higher numbers of motile spermatozoa were inseminated (27 vs 31%; P > 0.1). Based on these results, a single 0.5-mL straw dose containing 800 x 10(6) spermatozoa should be used and each insemination dose should contain approximately 320 x 10(6) motile spermatozoa. Fertility trials utilizing other freezing extenders are necessary before recommending a single 0.5-mL insemination dose for all freezing extenders.

Topics: Animals; Cryopreservation; Enzyme Inhibitors; Female; Gonadotropin-Releasing Hormone; Horses; Insemination, Artificial; Male; Pregnancy Rate; Random Allocation; Semen; Semen Preservation; Sperm Count; Spermatozoa; Triptorelin Pamoate

The synchrony of ovulation was examined in superstimulated heifers that had a downregulated pituitary gland and which were induced to ovulate by injection of exogenous LH. The pituitary was downregulated and desensitized to GnRH by treatment with the GnRH agonist deslorelin. Nulliparous heifers (3.5 yr old) at random stages of the estrous cycle were assigned to 1 of 3 groups, and on Day -7 received the following treatments: Group 1 (control, n = 8), 1 norgestomet ear implant; Group 2 (GnRH agonist, n = 8); Group 3 (GnRH agonist-LH protocol, n = 8), 2 deslorelin ear implants. Ovarian follicle growth in all heifers was superstimulated with twice-daily intramuscular injections of FSH (Folltropin-V): Day O, 40 mg (80 mg total dose); Day 1, 30 mg; Day 2; 20 mg; Day 3, 10 mg. On Day 2, all heifers were given a luteolytic dose of PGF (7 A.M.), Norgestomet implants were removed from heifers in Group 1 (6 P.M.). Heifers in Group 3 were given an injection of 25 mg, i.m. porcine LH (Lutropin) on Day 4 (4 P.M.). Ovarian follicle status was monitored at 8-h intervals from Day 3 (8 A.M.) to Day 6 (4 P.M.) using an Aloka Echo Camera and 7.5 MHz transducer. Heifers in Groups 2 and 3 exhibited estrus earlier (P < 0.05) than heifers in Group 1. Heifers in Group 2 did not have a preovulatory LH surge and they did not ovulate. Individual control heifers in Group 1 ovulated between 12 A.M. on Day 5 and 8 A.M. on Day 6. Heifers with deslorelin implants and injected with LH in Group 3 ovulated between 4 P.M. on Day 5 and 8 A.M. on Day 6. It was confirmed that superstimulated heifers with GnRH agonist implants can be induced to ovulate with LH. It was also demonstrated that ovulation is closely synchronized after injection of LH. Thus, a single, fixed-time insemination schedule could be used in a GnRH agonist-LH superovulation protocol, with significant practical and economic advantages for superovulation and embryo transfer programs.

Topics: Animals; Cattle; Drug Implants; Enzyme Inhibitors; Estrus; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Ovulation; Ovulation Induction; Pituitary Gland, Anterior; Pregnenediones; Progesterone; Progesterone Congeners; Triptorelin Pamoate

The capacity of heifer calves of a late sexually maturing Zebu (Bos indicus) genotype to respond to superstimulation with FSH at a young age and in vitro oocyte development were examined. Some calves were treated with a GnRH agonist (deslorelin) or antagonist (cetrorelix) to determine whether altering plasma concentrations of LH would influence follicular responses to FSH and oocyte developmental competency. Brahman calves (3-mo-old; 140 +/- 3 kg) were randomly assigned to 3 groups: control (n = 10); deslorelin treatment from Day -8 to 3 (n = 10); and cetrorelix treatment from Day -3 to 2 (n = 10). All calves were stimulated with FSH from Day 0 to 2, and were ovariectomized on Day 3 to determine follicular responses to FSH and to recover oocytes for in vitro procedures. Before treatment with FSH, heifers receiving deslorelin had greater (P < 0.001) plasma LH (0.30 +/- 0.01 ng/ml) than control heifers (0.17 +/- 0.02 ng/ml), while plasma LH was reduced (P < 0.05) in heifers treated with cetrorelix (0.13 +/- 0.01 ng/ml). Control heifers had a surge release of LH during treatment with FSH, but this did not occur in heifers treated with deslorelin or cetrorelix. All heifers had large numbers of follicles > or = 2 mm (approximately 60 follicles) after superstimulation with FSH, and there were no differences (P > 0.10) between groups. Total numbers of oocytes recovered and cultured also did not differ (P > 0.05) for control heifers and heifers treated with deslorelin or cetrorelix. Fertilization and cleavage rates were similar for the 3 groups, and developmental rates to blastocysts were also similar. Zebu heifers respond well to superstimulation with FSH at a young age, and their oocytes are developmentally competent.

Topics: Animals; Cattle; Enzyme Inhibitors; Female; Fertilization in Vitro; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormone Antagonists; Linear Models; Luteinizing Hormone; Male; Oocytes; Ovarian Follicle; Ovariectomy; Progesterone; Radioimmunoassay; Random Allocation; Superovulation; Triptorelin Pamoate

The objectives of this study were to investigate the effect of a synthetic GnRH-agonist (Deslorelin) implant on CL function and follicle dynamics when administered 48 h after PGF2 alpha, in a timed-insemination protocol, and to determine if the incorporation of a Deslorelin implant into a timed-insemination protocol to synchronize ovulation would be beneficial to the establishment of pregnancy. In Experiment 1, 15 non lactating cyclic Holstein cows received Buserelin (8 micrograms, i.m.) on Day-9, Lutalyse (25 mg, i.m.) on Day-2, and then on Day 0 received either a Deslorelin implant (700 micrograms, s.c.; n = 5), Buserelin (8 micrograms, i.m.; n = 5), or no treatment (control; n = 5). Blood samples were collected on Days-9, -2, 0 and thereafter daily until the next ovulation. Ovaries were scanned by ultrasound on Days-9, -2, 0, 1 (day of ovulation) and 3 times a week thereafter until a subsequent ovulation. From Days 0 to 15, the rate of increase of plasma progesterone (P4) was greater (P < 0.01) for Deslorelin than for control and Buserelin. Establishment of the first-wave dominant follicle (FWDF) as a Class 3 (> 9 mm) follicle was delayed (P < 0.01) with Deslorelin (14.2 +/- 1.3 d) compared with the control (4.6 +/- 1.3 d) and Buserelin (5.0 +/- 1.5 d) treatments. The FWDF resumed growth after Day 13 in all 5 Deslorelin-treated cows, and 2 cows ovulated spontaneously. In 1 Deslorelin-treated cow, the FWDF regressed, and a second-wave dominant follicle ovulated, while 2 other Deslorelin cows failed to ovulate until after Day 36. The cumulative numbers of Class 2 and 3 follicles was lowest in the Deslorelin group (P < 0.01), while the cumulative number of Class 1 follicles was highest (Deslorelin > Buserelin > Control; P < 0.01). The number of days to CL-regression and days to subsequent estrus did not differ (P > 0.05) among treatments. In Experiment II, 16 lactating potentially subfertile (body condition score 2.25) cows received Cystorelin (100 micrograms, i.m.; Day-9), Lutalyse (25 mg, i.m.; Day-2), and either a Cystorelin injection (100 micrograms, i.m.; n = 8) or Deslorelin implant (700 micrograms, s.c.; n = 8) on Day 0 and inseminated 16 h later. Deslorelin-treated cows had a higher plasma P4 concentration between Days 0 and 16 (P < 0.05) than the 2 other groups, and 5 of the 8 cows in this group were pregnant (Day 45, palpation) compared with 1 of 8 cows in the Cystorelin group (P < 0.05). Incorporation of a Deslorelin implant into a timed-insemi

Topics: Animals; Buserelin; Cattle; Corpus Luteum; Drug Implants; Female; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Luteolysis; Ovarian Follicle; Ovary; Pregnancy; Progesterone; Triptorelin Pamoate; Ultrasonography

It was the objective of this study to determine whether [des-Gly10, D-Trp6]LHRH ethylamide, an LHRH agonist known as deslorelin, is degraded by the rabbit conjunctiva. Intact conjunctiva was incubated with deslorelin either alone or in the presence of 0.1 mM ouabain, 0.1% 2,4-dinitrophenol, 0.1 mM phosphoramidon, 0.1 mM N-tosyl-L-phenylalanine chloromethylketone (TPCK), 2% EDTA, 1% ZnCl2, 0.1% dithiothreitol (DTT), or 0.1% N-ethylmaleimide (NEM) at 37 degrees C. Furthermore, deslorelin alone was incubated with conjunctiva at 4 degrees C. All incubation solutions were made isotonic, and the pH was adjusted to 5.0. A reversed-phase HPLC was used to analyze supernatants collected at the end of 90 min. Deslorelin metabolism was inhibited at low temperature, as suggested by the disappearance of metabolite peaks at low temperature. Both ouabain and dinitrophenol failed to alter the intact drug remaining in the supernatant, indicating that energy-dependent cellular uptake of deslorelin is unlikely in the conjunctiva. Phosphoramidon- and TPCK- sensitive endopeptidases did not contribute to the observed metabolism, as suggested by the lack of effect of phosphoramidon and TPCK on deslorelin levels. DTT and NEM also failed to affect deslorelin levels. On the other hand, EDTA and ZnCl2 significantly elevated the intact deslorelin levels by 61 and 53%, respectively, and almost completely abolished the metabolite peaks, indicating a possible role for either metaldependent peptidases or metallo-peptidases in the conjunctival metabolism of deslorelin.

Topics: 2,4-Dinitrophenol; Animals; Chlorides; Chromatography, High Pressure Liquid; Conjunctiva; Edetic Acid; Enzyme Inhibitors; Ethylmaleimide; Female; Glycopeptides; Gonadotropin-Releasing Hormone; In Vitro Techniques; Ouabain; Protease Inhibitors; Rabbits; Tosylphenylalanyl Chloromethyl Ketone; Triptorelin Pamoate; Zinc Compounds

The objective of this study was to determine the effects of inducing pituitary desensitization by treatment with an LHRH agonist (deslorelin) on reproductive hormone secretion and ovarian follicular status in heifer calves, before and during stimulation with FSH. The recovery and in vitro development of oocytes was also investigated. Brahman (Bos indicus) calves, 6 mo old, received either no treatment from Day 0 to Day 8 and injections of FSH on Days 9, 10, and 11 (controls, n = 10), or bioimplants of deslorelin on Day 0 and injections of FSH on Days 9, 10, and 11 (deslorelin calves, n = 10). Ovarian follicular characteristics were determined on Days -2, 0, and 8 by ultrasonography; follicle sizes (2-4 mm, 5-7 mm, 8-9 mm, or > or = 10 mm) were recorded. Ovaries were removed surgically on Day 12, surface follicle numbers and sizes were recorded, and oocytes were aspirated, graded (A-grade, B-grade, denuded, atretic), and prepared for in vitro fertilization and culture. Blood samples were taken throughout the experiment to monitor plasma concentrations of LH, estradiol-17 beta (estradiol) and progesterone. Treatment with deslorelin desensitized the pituitary in heifer calves and altered patterns of LH and estradiol secretion. There were no apparent consistent effects of deslorelin treatment on follicle numbers and growth. A higher number of combined A-grade and B-grade oocytes were obtained from heifers treated with deslorelin, which, in turn, resulted in twice the number of blastocysts. Treatment with an LHRH agonist provides a model for studying the hormonal requirements for follicle growth and in vivo oocyte maturation in heifer calves.

Topics: Analysis of Variance; Animals; Cattle; Drug Administration Schedule; Drug Implants; Enzyme Inhibitors; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Oocytes; Ovarian Follicle; Ovariectomy; Progesterone; Reference Values; Triptorelin Pamoate

Topics: Animals; Breeding; Dose-Response Relationship, Drug; Drug Implants; Enzyme Inhibitors; Female; Gonadotropin-Releasing Hormone; Horses; Ovulation; Ovulation Induction; Random Allocation; Triptorelin Pamoate

The requirement for endogenous LHRH and LH action in the maintenance of elevated plasma concentrations of testosterone in bulls receiving the LHRH agonist deslorelin was examined. In Experiment 1, bulls were either (i) left untreated (control); (ii) implanted with deslorelin; (iii) actively immunized against LHRH; or (iv) implanted with deslorelin and immunized against LHRH. Experiment 2 was of similar design to Experiment 1, except that bulls were immunized against LH in place of LHRH. In Experiment 1, plasma LH declined in bulls immunized against LHRH, but not in the bulls immunized against LHRH and implanted with deslorelin. Also in Experiment 1, plasma testosterone declined in bulls immunized against LHRH but was elevated in bulls treated with deslorelin and bulls treated with deslorelin and immunized against LHRH. In Experiment 2, bulls immunized against LH and treated with deslorelin had plasma concentrations of testosterone similar to controls, whereas bulls treated only with deslorelin had elevated plasma testosterone. It was concluded from these experiments that endogenous LHRH action was not required for increased steroidogenic activity in bulls treated with a LHRH agonist. However, circulating LH was necessary for increased plasma testosterone in bulls implanted with deslorelin. LH is therefore involved in mediating the response of bulls to treatment with deslorelin, either by acting directly at the testes or through a permissive role that allows a direct action of deslorelin at the testes.

Topics: Animals; Antibodies; Cattle; Drug Implants; Gonadotropin-Releasing Hormone; Immunization; Kinetics; Luteinizing Hormone; Male; Testosterone; Triptorelin Pamoate

Anterior pituitary gland contents of LH and LH beta- and alpha-subunit mRNAs, and circulating concentrations of LH and testosterone, were determined in bulls treated with the LH-releasing hormone (LHRH) agonist deslorelin. Brahman (Bos indicus) bulls (14-month-old) were allocated to two groups and received the following: Control (n = 5), no treatment; Deslorelin (n = 4), four deslorelin implants (approximately 200 micrograms total deslorelin/day) for 36 d. Plasma concentrations of LH were higher in bulls treated with deslorelin on Day 1, had returned to typical levels by Day 8, and did not differ for control bulls and bulls treated with deslorelin from Day 8 to Day 29. Pituitary content of LH on Day 36 was reduced (P < 0.001) in bulls treated with deslorelin (33 +/- 4 ng/mg) compared with control bulls (553 +/- 142 ng/mg). Relative pituitary content of LH beta-subunit mRNA was also reduced on Day 36 in bulls treated with deslorelin (Control, 0.65 +/- 0.10; Deslorelin, 0.22 +/- 0.04; P = 0.003). However, alpha-subunit mRNA relative content did not differ (Control, 0.73 +/- 0.15; Deslorelin, 1.06 +/- 0.12; P > 0.05). Plasma concentrations of testosterone were increased over the period of the experiment in the bulls treated with deslorelin compared with control bulls. This is the first demonstration of reduced pituitary content of LH beta-subunit mRNA and LH, and unaltered content of alpha-subunit mRNA, in bulls treated with LHRH agonist. This was associated with apparently typical plasma concentrations of LH and elevated plasma testosterone. The anterior pituitary in bulls treated with LHRH agonist, therefore, undergoes classical desensitization and downregulation, but plasma LH and testosterone are not suppressed.

Topics: Animals; Cattle; Glycoprotein Hormones, alpha Subunit; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Male; Pituitary Gland, Anterior; RNA, Messenger; Testosterone; Triptorelin Pamoate

The objective of this study was to determine whether [Des-Gly10, D-Trp6] LHRH ethylamide, a nonapeptide LHRH agonist known as deslorelin, is degraded by the rabbit nasal tissue. Deslorelin was incubated with nasal tissue either alone or in the presence of 0.1 mM ouabain, 0.1% 2,4-dinitrophenol, 0.1 mM phosphoramidon, 0.1 mM N-tosyl-L-phenylalanine chloromethylketone (TPCK) or 2% EDTA at 37 degrees C. Furthermore, deslorelin alone was incubated with nasal tissue at 4 degrees C. All incubation solutions were adjusted to isotonicity and pH 5.0. At the end of 90 min, the supernatants were analyzed using a reversed-phase HPLC. Metabolite peaks could be detected in all the above experiments except the low temperature study, suggesting inhibition of metabolism at low temperature. Intact drug remaining in the supernatant was elevated by about 32% by ouabain and dinitrophenol, suggesting that energy-dependent cellular uptake is likely for deslorelin. Phosphoramidon and TPCK failed to alter deslorelin levels, suggesting that phosphoramidon and TPCK sensitive endopeptidases did not contribute to the observed deslorelin metabolism. However, EDTA significantly elevated the intact deslorelin levels in a dose-dependent manner, with an elevation of 113% with 2% EDTA. With 2% EDTA, the metabolite peaks almost completely disappeared, indicating a possible role for either metal-activated peptidases or metallo-endopeptidases in the nasal metabolism of deslorelin.

Topics: Amino Acid Sequence; Animals; Chromatography, High Pressure Liquid; Enzyme Inhibitors; Female; Gonadotropin-Releasing Hormone; Molecular Sequence Data; Nasal Mucosa; Rabbits; Triptorelin Pamoate

The objective in this study was to characterize direct effects of the LHRH agonist, deslorelin, on anterior pituitary gland function in male cattle in the absence of gonadal feedback. Castrated bulls (steers), 30 mo old, were allocated to four groups: group 1, control, no treatment (n = 8); group 2, five deslorelin implants (approximately 250 micrograms total deslorelin/day) for 42 days (n = 8); group 3, control+ LHRH (50 micrograms i.m.) at weekly intervals (n = 3); group 4, five deslorelin implants+LHRH as for group 3 (n = 3). Plasma LH was similar (p > 0.05) for steers in groups 1 and 2 on Day 0 and lower (p < 0.05) for steers in group 2 on Day 4, and continued to decrease to Day 41 (group 1, 1.71 +/- 0.20 ng/ml [mean +/- SEM]; group 2, 0.38 +/- 0.03 ng/ml [p < 0.001]). Mean plasma concentrations of FSH were similar (p > 0.05) for steers in groups 1 and 2 on Day 0 and lower (p < 0.05) for steers in group 2 on Day 7, and declined to Day 41 (group 1, 43.5 +/- 3.9 ng/ml; group 2, 17.5 +/- 1.5 ng/ml [p < 0.001]). Steers in group 3 showed increases in plasma LH after injection of LHRH on all occasions, while steers in group 4 did not show increases in plasma LH from Day 14 onward. Mean relative pituitary contents (arbitrary units) of LH beta- and FSH beta-subunit mRNAs were reduced on Day 42 in steers treated with deslorelin (LH beta: groups 1 and 3, 1.56 +/- 0.27; groups 2 and 4, 0.08 +/- 0.01 [p < 0.001]; FSH beta: groups 1 and 3, 1.01 +/- 0.08; groups 2 and 4, 0.34 +/- 0.07 [p < 0.001]). However, alpha-subunit mRNA was similar for control steers and steers treated with deslorelin (groups 1 and 3, 1.00 +/- 0.11; groups 2 and 4, 0.86 +/- 0.12 [p > 0.1]). Pituitary content of LH, but not FSH, was reduced in steers treated with deslorelin. In summary, steers treated with deslorelin showed desensitization to natural LHRH, and this was associated with reduced pituitary contents of LH and FSH beta-subunit mRNAs, a reduction in pituitary content of LH, and decreases in plasma concentrations of LH and FSH. This demonstrated, for the first time, a direct action of LHRH agonist on LH and FSH beta-subunit gene expression in cattle, independent of gonadal feedback. Also, there was a differential effect of treatment with deslorelin on gonadotropin alpha- and beta-subunit mRNA contents in the anterior pituitary.

Topics: Animals; Cattle; Drug Implants; Follicle Stimulating Hormone; Follicle Stimulating Hormone, beta Subunit; Glycoprotein Hormones, alpha Subunit; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Male; Orchiectomy; Pituitary Gland, Anterior; RNA, Messenger; Triptorelin Pamoate

Young bulls were treated with graded dosages of the LHRH agonist deslorelin to ascertain 1) whether increased testosterone secretion persisted over a wide dose range of agonist; 2) whether elevated testosterone was maintained long-term and, if so, what effects there were on reproductive function; and 3) what pituitary responses to exogenous LHRH occurred in intact and castrated bulls receiving deslorelin. In three experiments, bulls received dosages of agonist ranging from approximately 0.15 to 29.0 micrograms deslorelin/kg live weight/day, by means of either bioimplants or injections. At all dosages, deslorelin induced an acute increase in plasma LH concentrations that declined after 24 h but remained at greater concentrations than in controls, although the differences were relatively small. Profiles of LH in bulls treated with deslorelin were characterized by tonic secretion with no clear evidence of LH pulses. Plasma testosterone concentrations were increased at all dosages of deslorelin and in one experiment remained greater than in controls for over 100 days of treatment. This increase was associated with an increase in the rate of testis growth; however, there were no apparent improvements in semen parameters. Bulls receiving deslorelin did not show a typical postcastration rise in plasma LH concentrations, and neither intact nor castrated bulls receiving deslorelin showed an increase in plasma LH after injection of natural sequence LHRH. The absence of endogenous LH pulses and lack of response to exogenous LHRH suggested that the anterior pituitary in bulls receiving LHRH agonist becomes desensitized. However, LH secretion persisted in a tonic manner and was associated with elevated plasma testosterone concentrations. The failure of both intact and castrated bulls receiving deslorelin to respond to exogenous LHRH suggested direct effects of deslorelin on the pituitary, rather than an interaction with steroid feedback.

Topics: Animals; Cattle; Drug Implants; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Male; Orchiectomy; Pituitary Gland; Testosterone; Triptorelin Pamoate

The objective in this study was to evaluate pituitary and testicular function in young bulls during and after treatment with the LHRH agonist deslorelin. The primary focus was to ascertain the period required for a return to typical LH and testosterone secretion after cessation of treatment with deslorelin, in order to establish whether desensitization was a phenomenon restricted to the pituitary or also occurred at the testes. Brahman bulls, 13.0 +/- 0.6 mo of age and 224 +/- 5 kg, were allocated to four groups and received treatment as follows: group C (n = 5), control, received no treatment; group C + LHRH (n = 5), control, received LHRH tests (50 micrograms LHRH i.m.) at the same times as group D + LHRH below; group D (n = 5), received deslorelin (approximately 200 micrograms/day) for 28 days; group D + LHRH (n = 5), received deslorelin for 28 days and were given LHRH test (50 micrograms LHRH i.m.) on Day 28 of treatment and on Days 2, 4, 8, 12, 16, and 20 after treatment. Deslorelin induced acute increases (p < 0.01) in plasma concentrations of LH and testosterone within 2 h, after which concentrations of both hormones declined by 24 h. From Day 6 to Day 28 of the treatment period, plasma LH concentrations were similar for treated and control bulls. During the same period, concentrations of plasma testosterone were greater (p < 0.01) in treated than in control bulls. Mean concentrations of both LH and testosterone were lower in treated than in control bulls for approximately one week after cessation of deslorelin treatment. Bulls treated with deslorelin did not exhibit a release of LH in response to exogenous LHRH on Day 28 of treatment. A relatively small but significant (p < 0.05) release of LH occurred on Day 4 after cessation of treatment with deslorelin (group D + LHRH, 0.49 +/- 0.11 ng/ml; group C + LHRH, 7.17 +/- 0.90 ng/ml). LH release in response to LHRH in bulls previously treated with deslorelin increased to Day 12 and then remained constant to Day 20 after cessation of treatment. However, LH release in these bulls remained significantly lower compared with that of control bulls during the 20 days after cessation of treatment with deslorelin. Bulls treated with deslorelin had a typical release of testosterone after administration of LHRH on Days 2-20 after discontinuation of treatment, even though there were relatively small releases of LH. Therefore, the pituitary in bulls remained desensitized to LHRH for at least 20 days after cessation

Topics: Amino Acid Sequence; Animals; Cattle; Drug Implants; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Male; Molecular Sequence Data; Pituitary Gland; Radioimmunoassay; Testis; Testosterone; Triptorelin Pamoate

Pituitary function, ovarian follicle growth, and plasma steroid concentrations were determined in prepubertal heifers during and after treatment with the LHRH agonist deslorelin. Brahman heifers, 13 mo of age and 204 +/- 5 kg, were allocated to 4 groups with treatments as follows: group C (n = 6), control, received no treatment; group C + LHRH (n = 6), control, received LHRH tests at the same times as group D + LHRH below; group D (n = 6), received deslorelin (approximately 300 micrograms/day) for 28 days; group D + LHRH (n = 6), received deslorelin for 28 days were given LHRH tests (50 micrograms LHRH i.m.) on Day 28 of treatment and on Days 2, 4, 8, 12, 16, and 20 after treatment. Number and size of ovarian follicles were determined by rectal ultrasonography. Deslorelin induced an increase in plasma concentrations of LH within 2 h (p < 0.001); LH remained greater (p < 0.05) for heifers treated with deslorelin for 48 h, but from Day 4 to 28 of treatment, LH in treated and control heifers did not differ. Ovarian follicles of heifers treated with deslorelin were characterized by increased (p < 0.05) maximum size, and also tended to have a greater rate of growth, compared with those of control heifers. Heifers treated with agonist had greater (p < 0.05) plasma concentrations of 17 beta-estradiol from Day 0 to 28 of treatment, and 17 beta-estradiol in these heifers showed cyclical fluctuations that appeared to be related to cycles of growth and regression of ovarian follicles. After cessation of deslorelin treatment, plasma LH was similar for heifers in group C and group D. Heifers in group C + LHRH had significant (p < 0.05) LH responses to exogenous LHRH at all times. In contrast, heifers in group D + LHRH did not show an LH release in response to exogenous LHRH on Day 28 of treatment and also failed to have a significant (p < 0.05) release of LH until Day 12 after treatment. A significant increase in plasma 17 beta-estradiol after LHRH injection also occurred on Day 12 after treatment in heifers in group D + LHRH. The findings indicated that LHRH agonist treatment in prepubertal heifers is associated with an acute LH response followed by a return of LH to concentrations similar to those of control heifers. Size of the largest ovarian follicle is greater in heifers treated with LHRH agonist and is associated with increased plasma concentrations of 17 beta-estradiol. After cessation of agonist treatment, the pituitary remains desensitized to LHRH for approx

Topics: Amino Acid Sequence; Animals; Cattle; Estradiol; Female; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Molecular Sequence Data; Ovarian Follicle; Ovary; Pituitary Gland; Progesterone; Radioimmunoassay; Triptorelin Pamoate; Ultrasonography

Ovuplant (deslorelin STI), when used in estrous mares with a follicle > or = 30 mm, reliably causes acceleration of ovulation and assurance that > 80% of the treated mares will ovulate within 48 hours. Time to ovulation is reduced by 30 hours or more. Treatment with Ovuplant had no adverse effects on pregnancy rates and did not increase the rate of early twin pregnancies. Treatment did not cause local or systemic side effects beyond short-term local irritation. Mares can be treated repeatedly without the development of tolerance or the loss of effectiveness. These studies have shown that Ovuplant can be used with a high level of assurance for success in the equine breeding industry. This will allow to reap benefits by reducing the number of breedings, saving stallion power and avoiding unnecessary inseminations. The mare has come an important step closer to a safe and effective management of ovulation.

Topics: Animals; Chorionic Gonadotropin; Dose-Response Relationship, Drug; Drug Implants; Estrus; Female; Gonadotropin-Releasing Hormone; Horses; Insemination, Artificial; Male; Ovulation; Pregnancy; Pregnancy, Animal; Triptorelin Pamoate

A case is presented of a middle-aged man suffering from stage D2 prostate cancer with pulmonary metastases who responded favorably, first, to endocrine combination therapy with the antiandrogen flutamide and an LHRH agonist for 5.5 years, and, second, to the subsequent withdrawal of Flutamide at the time of the progression of the disease. This case has several exceptional features: absence of bone metastases, pulmonary metastatic nodules characterized as focal neuroendocrine differentiation, and a positive response to antiandrogen withdrawal upon relapse of metastases after initial positive response. The concept of escape to androgen blockade and development of androgenic hypersensitivity is discussed.

Topics: Acid Phosphatase; Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Bone and Bones; Flutamide; Gonadotropin-Releasing Hormone; Humans; Lung Neoplasms; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Sputum; Tomography, X-Ray Computed; Triptorelin Pamoate

Topics: Animals; Drug Implants; Female; Gonadotropin-Releasing Hormone; Horses; Luteinizing Hormone; Ovarian Follicle; Ovulation; Ovulation Induction; Random Allocation; Time Factors; Triptorelin Pamoate; Ultrasonography

Each peptide bond in leuprolide (1), deslorelin (13), and nafarelin (24) was separately substituted with N-methyl. The synthesized compounds were tested for in vitro receptor binding, LH release, and stability against chymotrypsin and intestinal degradation. The NMe-Ser4 (30), NMe-Leu7 (33), and Sar10 (35) analogues of nafarelin had pD2 values 2-, 20-, 9-fold higher than their respective parent. All the other N-methyl agonists were less active. For the first time, conversion of LHRH agonists to antagonists was observed as a result of N-methyl substitution in the peptide backbone. [NMe-Phe2,DLeu6,Pro9NHEt]LHRH (4), [NMe-1Nal3,DLeu6,Pro9NHEt]LHRH (6), [NMe-His2,DTrp6,Pro9NHEt]LHRH (14), [NMe-Phe2,DNal6]LHRH (27), and [D2Nal6,NMe-Arg8]LHRH (34) exhibited antagonist responses. Substitutions of NMe-1Nal3, NMe-Ser4, or NMe-Tyr5 in leuprolide rendered the 3-4 peptide bond in these compounds completely stable to chymotrypsin. Examination of the three-dimensional structure of leuprolide when bound to the active site of chymotrypsin, reveals the NH's of residues 3 and 5 are involved in hydrogen bond interactions with the enzyme. N-Methylation at these positions is not only disrupting the hydrogen bond interactions, but is also sterically preventing the substrate from fitting in the enzyme's active site. All the compounds in the leuprolide series were also tested against intestinal degradation using an in vitro rat jejunum sac assay. In this model the pattern of stabilization was similar, but not identical, to that against chymotrypsin. The pharmacokinetics of all the analogues in the leuprolide series and of several others in the deslorelin and nafarelin series were determined. The clearance values of all the three NMe-Tyr5 analogues, 8, 20, and 31 were lower than their respective parents. These slower clearances suggest lower rates of metabolism.

Topics: Amino Acid Sequence; Animals; Chymotrypsin; Gonadotropin-Releasing Hormone; In Vitro Techniques; Intestinal Mucosa; Leuprolide; Luteinizing Hormone; Male; Methylation; Models, Molecular; Molecular Sequence Data; Nafarelin; Peptides; Pituitary Gland; Rats; Receptors, LHRH; Structure-Activity Relationship; Triptorelin Pamoate

A small, biocompatible and short-term implant releasing 1.5 mg or 2.25 mg of the GnRH analogue deslorelin was evaluated in 140 Hanoverian (warm blooded) mares during the 1990 breeding season (Study I). Mares in oestrus and with a follicle 40 +/- 2 mm in diameter were assigned alternately to treatment (70) or remained as untreated controls. Implants were administered subcutaneously, and intervals to ovulation determined by rectal examination and ultrasound at 12-h intervals. Since results with both doses of deslorelin were similar, data were pooled. Deslorelin implantation resulted in ovulations in 65 of 70 mares within 48 h (93%), while only 5 of 70 control mares ovulated within the same time period (7%) (P < 0.01). Most induced ovulations (63%) occurred 36-48 h after implantation. In Study II, 4 groups of 12 Hanoverian mares each were treated with 3,000 or 5,000 iu hCG, or a 2.25 mg deslorelin implant, or received placebo. All treatments resulted in 100% ovulations within 48 h, versus 25% ovulations in controls (P < 0.01), and 63%, 75% and 86% of these ovulations occurred 36-48 h after treatment with 3,000 and 5,000 iu hCG and deslorelin respectively. Hormonal response to deslorelin in treated mares, sampled every 12 h, consisted of elevations of FSH and LH concentrations of > 200% and > 300% baseline values at 12 h (P < 0.001), of 67% and 79% at 24 h (P < 0.01) and of 35% and 49% at 48 h (P < 0.05), respectively. No local reactions at the implantation site were observed.

Topics: Alcohol Dehydrogenase; Animals; Chorionic Gonadotropin; Drug Implants; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Horses; Luteinizing Hormone; Ovulation; Progesterone; Time Factors; Triptorelin Pamoate

A series of 115 previously untreated patients displaying clinical stage C prostatic carcinoma with no evidence of distant metastases received combination therapy using the antiandrogen flutamide and the LHRH agonist [D-Trp6, des-Gly-NH(2)10]LHRH ethylamide; the average follow-up was 3.9 years. Twenty-eight patients showed treatment failure with a probability of disease-free survival of 91.2% at 2 years. Twenty patients died from prostate cancer and 10 from other causes, the survival probability being 93.4% at 2 years. Local control was achieved rapidly in all patients. Urinary obstruction and hydronephrosis were corrected in all cases. When compared with data obtained after single endocrine therapy (orchiectomy or oestrogens) or radiotherapy, the treatment failure rate at 2 years was more than 3.0-fold lower after combination therapy (8.8%) than monotherapy (28.4%). The death rate 2 years after the start of combination therapy was 6.6% and was on average 22.2% (3.6-fold higher) in the studies using monotherapy (orchiectomy or oestrogens) or radiotherapy. The present data suggest that treatment of prostate cancer with combination therapy before clinical evidence of dissemination of disease permits more efficient control of local disease and a decreased rate of progression to metastatic disease.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Carcinoma; Drug Therapy, Combination; Flutamide; Gonadotropin-Releasing Hormone; Humans; Male; Middle Aged; Prostatic Neoplasms; Survival Rate; Triptorelin Pamoate

Precocious puberty often leads to short adult height. Since the introduction of luteinizing hormone-releasing hormone (LHRH) agonist treatment for LHRH-dependent precocious hormone (LHRH) agonist treatment for LHRH-dependent precocious puberty in 1979, several reports have shown increased predicted height among LHRH agonist-treated children. To determine whether the LHRH agonist deslorelin can normalize the adult height of children with precocious puberty, we are conducting a long-term pilot study involving 161 children. This report describes the first 44 children to have attained final or proximate adult height. These children were 7.1 +/- 1.2 (mean +/- SD) yr old (bone age 11.8 +/- 1.5 yr) and had been in puberty for 3.1 +/- 0.3 yr at the start of treatment. They were treated with deslorelin (4 micrograms/kg/day sc) for 4.1 +/- 1.3 yr and had been withdrawn from treatment for an average of 2.4 yr at the time of this study (age 13.6 +/- 0.9 yr). Fourteen of the 44 children, who had grown less than 0.5 cm during the previous year, were considered to have attained adult height. The other 30 children had achieved 98.6% of predicted mature height (Bayley-Pinneau method) and were considered to be at proximate adult height. The final or proximate adult height of these 44 children averaged -1.1 SD compared to the adult height of the normal population. This height was significantly greater than the pretreatment height (-1.1 vs. -2.0 SD, P less than 0.01), but significantly less than both the predicted height at the end of treatment (-1.1 vs. -0.5 SD, P less than 0.01) and the target height derived from the mean height of the parents adjusted for the sex of the child (-1.1 vs. 0.1 SD, P less than 0.01). The observation that the Bayley-Pinneau height prediction at the end of treatment overestimated the actual adult height emphasizes the importance of using final height data to assess the ultimate impact of LHRH agonist treatment. It also indicates the need for caution when predicting the adult height of children who are still receiving treatment. We conclude that deslorelin has improved the adult height of these patients but has not fully restored height to the patients' genetic potential. We hypothesize that further improvement will be seen in patients who are treated with less delay and at a younger bone age.

Topics: Body Height; Bone Development; Child; Female; Forecasting; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Male; Puberty, Precocious; Time Factors; Triptorelin Pamoate

The histochemical activities of the enzymes alcohol dehydrogenase with propanol (A-D I) and isopropanol (A-D II) as substrates, 3- beta-hydroxysteroid dehydrogenase (3 beta .OHST-D), nicotinamideadenine dinucleotide phosphate (reduced form)-tetrazolium reductase (NADPH2-TR) and glucose-6-phosphate dehydrogenase (G6P-D) were studied in the testis of 6 cats daily injected with 20 micrograms/kg of the LHRH-analogue DTRP6-DGLY-10, LHRH-ethylamide (LHRH-A Group) and 3 cats injected with saline during 67 days. A morphometric analysis was done to evaluate the activity of the enzymes, its distribution and volume fractions of the Leydig cells with every activity. A-D II displayed a significant inhibition in the Leydig cells of the LHRH-A Group. There were no changes in the activities of G6P-D, 3 beta .OHST-D and NADPH2-TR, but it was possible to disclose some reduction of the volume fraction of the Leydig cells when the first two enzymes were used as its marker. This study corroborates that A-D II is a reaction in the pathway of steroidogenesis but does not explain whether it corresponds actually to 20-22 desmolase as proposed in the work by Hardonk (1965) or to another reaction linked to the activities of the cytochromes P450.

Topics: Alcohol Dehydrogenase; Animals; Cats; Gonadotropin-Releasing Hormone; Histocytochemistry; Leydig Cells; Male; Triptorelin Pamoate