trelstar and Body-Weight

GnRH analogues (GnRHa) are the treatment of choice for central precocious puberty (CPP), with the main objective to recover the height potential compromised by the premature fusion of growth cartilages. The aim of this review was to analyze long-term effects of GnRHa on height, body weight, reproductive function, and bone mineral density (BMD) in patients with CPP, as well as the potential predictors of outcome. Because randomized controlled trials on the effectiveness and long-term outcomes of treatment are not available, only qualified conclusions about the efficacy of interventions can be drawn. GnRHa treatment appears to improve adult height in girls with CPP, especially if diagnosed before the age of 6, whereas a real benefit in terms of adult height is still controversial in patients with the onset of puberty between 6 and 8 years of age. No height benefit was shown in patients treated after 8 years. Gonadal function is promptly restored in girls after cessation of treatment, and reproductive potential appears normal in young adulthood. Data are conflicting on the long-term risk of polycystic ovarian syndrome in both treated and untreated women. Fat mass is increased at the start of treatment but normalizes thereafter, and GnRHa itself does not seem to have any long-term effect on BMI. Similarly, analogue treatment does not appear to have a negative impact on BMD. Owing to the paucity of data available, no conclusions can be drawn on the repercussions of CPP and/or its treatment on the timing of menopause and on the health of the offspring.

Topics: Body Height; Body Weight; Bone Density; Child; Child, Preschool; Delayed-Action Preparations; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Polycystic Ovary Syndrome; Puberty, Precocious; Reproductive Health; Treatment Outcome; 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

Central precocious puberty (CPP) is treated with GnRH analogues to stabilize secondary sexual characteristics and to prevent loss of final height (FH) due to accelerated bone maturation. However, some studies suggest that FH is not always improved and that treatment may induce excessive weight gain. We analysed data from 19 girls treated for CPP with monthly injections of 3.75 mg triptorelin. Pubertal development, bone age, height, weight and body mass index (BMI) were evaluated at start (chronological age: 7.8 +/- 1.8 yrs, mean +/- SD), at the end of treatment (10.6 +/- 1.1 yrs) and at FH (14.9 +/- 2.5 yrs). At start of treatment, breast (B) development was B3 (from 2 to 4), bone age 10.6 +/- 1.7 yrs, height 2.1 +/- 1.1 SDS and BMI 1.3 +/- 0.8 SDS. Treatment stabilized or reduced breast development and decreased bone maturation. Final height was 162.3 +/- 6.6 cm (0.0 +/- 1.1 SDS) and was comparable to predicted adult height at the start of treatment and to corrected mid-parental height. BMI SDS at the start, the end of treatment and at final evaluation were 1.3 +/- 0.8, 1.6 +/- 0.8 and 1.4 +/- 0.9 SDS. In conclusion, in our girls with central precocious puberty, treatment with GnRH agonist stabilized or decreased breast development and stabilized bone maturation, but did not increase neither final height nor weight. Aspects other than height should also be taken into account when considering treatment of children with precocious puberty.

Topics: Body Height; Body Weight; Bone Development; Breast; Child; Female; Humans; Luteolytic Agents; Puberty, Precocious; Triptorelin Pamoate

Early and fast puberty (EFP) in girls, defined as pubertal onset at age 8-9 yr, with an accelerated course, may cause compromised final height (FHt) and psychosocial distress. Treatment with a gonadotropin-suppressive agent is controversial, because the improvement in FHt is equivocal and there may be risk of obesity. We analyzed the data of 126 girls with EFP: 63 treated with GnRH analog (GnRHA) since Tanner stage 3, for 2-4 yr; and 63 untreated. Age at onset of puberty; accelerated time of transition from Tanner stage 2 to 3 (<1.3 yr); and clinical, hormonal and sonographic findings were similar in the 2 groups. The girls given GnRHA treatment had a significantly prolonged pubertal course, compared with the accelerated course in the untreated girls (4.7 +/- 0.4 vs. 2.45 +/- 0.4 yr, P < 0.001). After therapy, they reached Tanner stages 4 and 5 and FHt at a significantly older age than the untreated group (P < 0.001), and their menarche was delayed (12.8 +/- 0.6 vs. 10.8 +/- 0.5 yr, P < 0.001). However, the different pace of puberty in the 2 groups did not change the total pubertal growth and the bone maturation rate. The Ht gain from Tanner stage 3 to 4 (10.4 +/- 2.7 vs. 11.2 +/- 3.1 cm) and from Tanner stage 4 to FHt (8.2 +/- 2.7 vs. 8.8 +/- 3.6 cm) was similar in the treated and untreated girls, as were absolute Ht and bone age at each pubertal stage. The weight gain of the treated girls was more pronounced during treatment (P = 0.0016), but it was arrested after discontinuation of therapy; and by the time FHt was reached, the body mass index was similar in the 2 groups. The treated and untreated girls achieved a similar mean FHt, which was not significantly different from their respective mean target Ht (THt). Individual analysis revealed that 70% of the treated girls and 67% of the untreated girls attained their THt range (THt +/- 0.5 SD) or surpassed it. In conclusion, treatment with GnRHA affected only the pace of EFP. The similar Ht gain and bone maturation rate at each pubertal stage in the treated and untreated girls may suggest that the total pubertal growth is not dependent on pubertal duration and pace and is probably determined already at the onset of the normal pubertal development. The treatment did not compromise the FHt and did not cause long-lasting obesity. Therefore, GnRHA therapy may be suggested for use in girls who have psychosocial difficulties in coping with EFP.

Topics: Body Height; Body Weight; Bone Development; Child; Female; Gonadotropin-Releasing Hormone; Humans; Puberty, Precocious; 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

Topics: Body Weight; Drug Therapy, Combination; Female; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Infertility, Female; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome; 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

To evaluate the long-term efficacy of triptorelin 3.75 mg subcutaneously every 6 weeks on the final height in girls with idiopathic central precocious puberty (ICPP).. Forty females with ICPP received triptorelin 3.75 mg every 6 weeks subcutaneously in our hospital from 2002 to December 2010 and reached their final heights were enrolled. These patients were treated with triptorelin alone (group A, n=17) or triptorelin+recombinant human growth hormone (rhGH) (group B, n=23). Height, weight, annual growth velocity (GV), sexual development, predicted adult height (PAH), and adverse effects were observed. Bone age (BA) and height standard deviation score (SDS) were monitored yearly.. Final adult heights (FAHs) were 159.81±1.20 cm and 161.01±1.02 cm in group A vs. group B, which exceeded target height (THt) by 1.51±1.04 cm, 4.86±0.94 cm, respectively. The values of (FAH-THt), (FAH-PAH posttreatment) showed significant difference between the two groups (p<0.05). FAH was positively correlated with Ht SDS-BA at the end of treatment, THt, course of rhGH treatment, and age of menarche (r2=0.66). Body mass index (BMI) increased after treatment in group B. However, there was no significant tendency of increase compared with healthy children at the same age. Ages of menarche and time to menarche from discontinuation were 11.74±0.16 vs. 12.18±0.15 years and 17.41±1.69 vs. 14.71±1.04 months in two groups.. The FAH was improved effectively by triptorelin 3.75 mg subcutaneously every 6 weeks, and more height gain could be achieved when rhGH was used concomitantly. BMI maintained steadily and ovarian function restored quickly after treatment discontinuation with the age of menarche similar to that of normal children. Neither significant side effect nor polycystic ovary syndrome was observed.

Topics: Adolescent; Adult; Antineoplastic Agents, Hormonal; Body Height; Body Mass Index; Body Weight; Bone Development; Breast; Case-Control Studies; Child; Child, Preschool; Female; Humans; Infant; Injections, Subcutaneous; Menarche; Puberty, Precocious; Triptorelin Pamoate

Treatment of central precocious puberty (CPP) is the administration of GnRH analogs. Metabolic syndrome comprised metabolic disturbances that confer increased risk of (CVD) diabetes mellitus (DM) and cardiovascular disease. This study is a longitudinal prospective study in pediatric endocrinology clinic. 30 non-obese children with idiopathic CPP were involved. Total body weight, height, blood pressure, BMI and waist circumference of the patients along with their triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), fasting plasma sugar (FPS) were evaluated at the beginning and during 3 and 6 months GnRH analog therapy. All of the patients involved in this study were female with age 9.5±1.02 years. Waist circumference, weight and BMI were 69.3 cm, 37.21 kg, and 19.13 kg/cm(2) before therapy and 72.25 cm, 40.11 kg, and 19.54 kg/m(2) 6 months after therapy respectively. Mean systolic and diastolic blood pressure of the patients before therapy was 96.83 mmHg, 66mmHg and after 6 months therapy was 98.66 mmHg, 89.63 mmHg respectively. Mean TG, LDL, HDL and FPS were 90.06 mg/dl, 91.6 mg/dl, 43.7 mg/dl and 89.6 mg/dl before therapy and 96.4 mg/dl, 93.1 mg/dl, 44.7 mg/dl and 91.36 after 6 months therapy respectively. GnRH analog therapy doesn't cause metabolic syndrome after 3 and 6 month therapy but it may cause hyperlipidemia and central obesity.

Topics: Biomarkers; Blood Glucose; Blood Pressure; Body Height; Body Mass Index; Body Weight; Child; Female; Gonadotropin-Releasing Hormone; Humans; Hyperlipidemias; Lipids; Longitudinal Studies; Metabolic Syndrome; Obesity, Abdominal; Prospective Studies; Puberty, Precocious; Risk Factors; Time Factors; Treatment Outcome; Triptorelin Pamoate; Waist Circumference

We studied the effect of gonadotropin-releasing hormone analogues (GnRHa) on weight gain as a possible side effect.. We analyzed longitudinally changes in BMI-SDS in 92 children [median age 8.0 years (IQR 7.1-8.9), 88% females, mean BMI-SDS 0.69 ± 1.30] with idiopathic central precocious puberty or early puberty treated with GnRHa. Furthermore, 25 overweight children with GnRHa were compared to 25 overweight children without GnRHa matched by age, gender, degree of overweight, and pubertal stage.. The matched overweight children without GnRHa demonstrated a significant increase in their BMI-SDS in the course of 1 year (+0.18 ± 0.22). Normal-weight children treated with GnRHa demonstrated a significant increase in BMI-SDS in the course of 1 year (+0.32 ± 0.66) in contrast to overweight children treated with GnRHa who showed a stable BMI-SDS (-0.02 ± 0.27). This significant difference in changes in BMI-SDS between normal-weight and overweight children treated with GnRHa was also observed at the end of GnRHa treatment and 6 months later (p < 0.001).. Change in weight status differed between overweight and normal-weight children during GnRHa treatment. We found no increased risk for the side effect of weight gain in overweight children treated with GnRHa.

Topics: Body Height; Body Mass Index; Body Weight; Child; Female; Gonadotropin-Releasing Hormone; Humans; Longitudinal Studies; Male; Overweight; Puberty, Precocious; Retrospective Studies; Triptorelin Pamoate; Weight Gain

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

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 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

Depot gonadotropin releasing hormone (GnRH) agonist (GnRHa) therapy is the treatment of choice for patients with central precocious puberty (CPP). It is still unclear whether long-term exposure to GnRHa is associated with impaired reproductive function in adulthood. The present study was performed on 46 women, former CPP patients, 12.5+/-3.7 years after the discontinuation of treatment with depot GnRHa. In a structured interview, we assessed general health status, clinical signs possibly associated with hyperandrogenism, menstrual cycle, gynaecological diseases and reproductive function. It appears that long-term treatment with depot GnRHa is safe and does not impair reproductive function. The risk of former CPP patients to develop hirsutism and/or polycystic ovary syndrome does not seem to be increased compared to the normal population but this issue needs to be addressed in further long-term follow-up studies.

Topics: Adult; Androgens; Body Height; Body Mass Index; Body Weight; Delayed-Action Preparations; Drug Administration Routes; Female; Fertility; Follow-Up Studies; Genital Diseases, Female; Gonadotropin-Releasing Hormone; Health Status; Humans; Hyperandrogenism; Interviews as Topic; Long-Term Care; Menstrual Cycle; Puberty, Precocious; Reproduction; Triptorelin Pamoate

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 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 objective of this study was to evaluate the characteristics of puberty and response to gonadotrophin-releasing hormone (GnRH) agonist treatment in adopted children compared with children with idiopathic precocious puberty (IPP).. We studied 17 girls with central IPP (group A) and 11 girls adopted from Asia and Central and South America (group B) with respect to auxological data at presentation of puberty and response to GnRH agonist treatment.. In adopted girls, age at onset of puberty was later and duration of treatment was shorter. At the start of treatment, height-standard deviation score (H-SDS) was +1.67 s.d. in group A. In group B, H-SDS was comparably increased (+0.04 s.d.) assuming that the mean H-SDS in their native country is lower than the mean on the Dutch curve. During treatment, H-SDS decreased in both groups. Group A reached a final height (FH) of 166.2 cm (-0.3 s.d.) and group B of 156.1 cm (-1.9 s.d.). Predicted adult height (PAH) at the start of treatment underestimated FH in group A and overestimated FH in group B. At the end of treatment, PAH overestimated FH in both groups. The SDS for weight was above the mean in both groups at the start of treatment and increased even more during treatment. The age of occurrence of menses after treatment was stopped was the same in both groups (12.7 and 12.8 Years respectively).. Despite the difference in timing of puberty between girls with IPP and adopted girls with early puberty, their response to treatment was similar in many aspects.

Topics: Adoption; Body Height; Body Weight; Child; Child, Preschool; Female; Gonadotropin-Releasing Hormone; Growth; Humans; Luteolytic Agents; Male; Menstrual Cycle; Puberty; Puberty, Precocious; Retrospective Studies; 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

Body composition changes with age and sex differences become significant only after puberty. Boys and girls before the age of 8 yr do not differ in fat, lean or bone mineral mass. Hormonal influences during pubertal development determine the physiological adult male and female body composition phenotype.. The aim of our study was to evaluate body composition changes due to central precocious puberty (PP) and the specific effects of therapy on these modifications.. Sixteen patients (14 girls, 2 boys) were included in the study. They were diagnosed as affected by idiopathic PP according to standard hormonal and clinical criteria; anatomic alterations of hypothalamus-hypophysis region were excluded by MRI. Mean age at diagnosis was 5.9 +/- 1.9 yr. All patients received GnRH analog (Leuprolide or Triptorelin) treatment subcutaneously every 4 weeks for at least 1 yr. Mean period of treatment was 3.4 +/- 1.9 yr. Standard anthropometry and body composition analysis were performed at baseline and every 6-12 months. A group of healthy subjects with normal timing of puberty was matched (for age or for pubertal stage) served as the control group (CA or CP, respectively).. Patients with PP showed at baseline a significant increase of BMI and relative body weight; lean and fat compartments were also increased but not significantly. During treatment, the PP group showed increased fat mass compared to CA (p<0.05), while no difference was found between PP and CP. Lean mass was similar to CA but lower than in CP (p<0.05). During treatment a significant increase in lean mass (both as total as well as limb mass) was observed. After stopping treatment there was no difference between PP and CP, except for lower lean mass (p<0.04).. When puberty occurs precociously, lean and fat mass are not significantly different from age-matched control subjects. Data collected during treatment confirm a shortening of prepubertal lean mass development and the block of further lean mass development due to puberty itself, while fat mass accumulation continues. The net result of these modifications determines a typical body composition pattern in PP patients, after the end of therapy: lean mass is reduced by a shortening of the prepubertal growing period and by the "menopausal effect" of treatment itself. Fat mass is increased as a consequence of therapy and could lead to future obesity.

Topics: Adipose Tissue; Anthropometry; Body Composition; Body Mass Index; Body Weight; Brain Diseases; Child, Preschool; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Puberty, Precocious; Triptorelin Pamoate

The results of hormonal examinations, measurements of dimensions of the uterus and leiomyomas, body weight, and also frequency of incurred climacteric signs in patients treated with Decapeptyl Depot 3.75 mg for three months are reported. Subjects consisted of 12 women, among whom nine were treated for leiomyomas and four for endometriosis (one patient also had leiomyomas). Based on examinations carried out, the biggest decrease of the uterus and leiomyomas was 13-17% observed just after two doses of analog, though after the end of treatment the dimensions of the uterus slowly increased. Therefore, 2-month therapy could be used successfully as preparation for further conservative surgical treatment. Significant increase of body weight in treated patients was not observed. In women with endometriosis pain symptoms in the hypogastric area and dyspareunia regressed during treatment and at the end were not observed. The disadvantages of therapy with Decapeptyl Depot 3.75 was the rapid occurrence of symptoms--climacteric signs, especially hot flashes--which were badly tolerated by patients. All these symptoms almost totally regressed one month after ending therapy.

Topics: Adult; Antineoplastic Agents, Hormonal; Body Weight; Delayed-Action Preparations; Endometriosis; Female; Humans; Leiomyomatosis; Middle Aged; Triptorelin Pamoate; Uterine Diseases; Uterine Neoplasms

In central precocious puberty (CPP), characterised by premature but otherwise normal puberty, the early onset of the pubertal growth spurt with increased height velocity results in premature epiphyseal closure with reduced final height. We examined the growth pattern in 11 patients (9 girls and 2 boys) with CPP treated with a long-acting gonadotropin-releasing hormone analogue (GNRHa). Every 28 days 75 micrograms of the GNRHa Triptorelin (Decapeptyl CR, Fa. Ferring) per kg body weight are given intramuscularly. We observed body height, height velocity, bone maturation (dBA/dCA) and predicted adult height in these patients for up to 4 years. Before treatment body height was markedly elevated (2.5 +/- 4.4 SD above the age appropriate mean); after two years of therapy it reached the normal range. Height velocity decreased significantly within the first six months of treatment and remained subsequently low (F = 7.59; p < 0.0001). In the first year on treatment bone maturation (dBA/dCA) dropped from 1.8 +/- 0.42 to 0.7 +/ 0.27 and in the second year to its lowest value of 0.3 +/- 0.13 (F = 2.35; p < 0.05). The predicted adult height increased from 154.5 +/- 4.0 cm at the beginning of treatment to 160.3 +/- 3.9 cm at the most recent follow-up examination. The present data indicate that treatment with a long-acting GNRHa markedly affects body growth in CPP by reducing height velocity and delaying bone maturation. The predicted adult height appears to increase, consequently.

Topics: Adolescent; Age Determination by Skeleton; Body Height; Body Weight; Bone Development; Child; Child, Preschool; Delayed-Action Preparations; Female; Follow-Up Studies; Gonadal Steroid Hormones; Humans; Injections, Intramuscular; Male; Puberty, Precocious; Sexual Maturation; Triptorelin Pamoate

Changes in bone mineral content induced by GnRH agonists were investigated by measuring total body bone mineral content (TBBM) and regional bone mineral content (BMC) (arms, legs, trunk, pelvis) and densities with dual energy X-ray absorptiometry in 25 premenopausal women before and after a 6-month treatment with gonadotropin-releasing hormone (GnRH) agonists. Biological markers of bone remodeling, estrogens, luteinizing hormone, and follicle-stimulating hormone were also measured. Weight and body mass index increased significantly after treatment (P < 0.05), and TBBM, corrected for weight (TBBM/W), decreased (P < 0.001). The changes in BMC that we observed ranged from +2.5% to -6.9%. The greatest decrease in regional BMC occurred in the trunk (4.4%, P < 0.001), with TBBM decreasing by 2.1% (P < 0.001). No significant changes were observed in the limbs. Tartrate-resistant acid phosphatase (TRAP) increased significantly after treatment (P < 0.001) and a significant negative correlation between TRAP and TBBM (P < 0.001) and between TRAP and estradiol (P < 0.001) were observed before treatment. The lack of changes observed in the BMC of the limbs indicate that GnRH agonists cause a preferential loss of BMC in trunk osseous structures, a situation similar to that of the first years of menopause.

Topics: Absorptiometry, Photon; Acid Phosphatase; Adult; Body Mass Index; Body Weight; Bone Density; Bone Remodeling; Estrogens; Female; Humans; Triptorelin Pamoate

Female BDF1 mice inoculated with MXT (3.2) estrogen independent mouse mammary carcinoma were treated for three weeks with microcapsules of the luteinizing hormone-releasing hormone (LH-RH) agonist [D-Trp6]LH-RH, the antagonist SB-75, the somatostatin analog RC-160, or combinations. The lack of estrogen dependence of the tumor was proved by bilateral surgical ovariectomy, which had no effect. In two experiments, treatment with 25 micrograms/day doses of each analog alone resulted in a significant inhibition of tumor growth as shown by a 40-53% inhibition of tumor volumes, 38-43% decrease in tumor weights, and histological signs of tumor regression. However, the combination of SB-75 or [D-Trp6]LH-RH with somatostatin analog RC-160 caused greater reduction of tumor volume (68 and 61%) or tumor weights (59 and 56%), than single analogs, and histologically the occurrence of apoptosis and decrease in AgNOR numbers was more pronounced in the groups receiving combination therapy. Specific binding sites for [D-Trp6]LH-RH, EGF, and IGF-I were demonstrated in the tumor membranes. The binding capacity of LH-RH receptors was decreased by treatment with the analogs, the greatest down-regulation being caused by combination therapy. A significant decrease in EGF binding capacity was observed after treatment with the LH-RH analogs, alone or especially in combination with somatostatin analog RC-160. The combination of these analogs also caused a reduction in IGF-I receptors. The finding that LH-RH agonists and antagonists and somatostatin analogs inhibit the growth of estrogen independent mammary tumors, and that combinations are more effective than single analogs, might be of practical importance in human breast cancer therapy.

Topics: Amino Acid Sequence; Animals; Antineoplastic Combined Chemotherapy Protocols; Body Weight; Drug Compounding; Drug Screening Assays, Antitumor; Drug Synergism; Female; Gonadotropin-Releasing Hormone; Mammary Neoplasms, Experimental; Mice; Molecular Sequence Data; Neoplasm Proteins; Receptors, Cell Surface; Somatostatin; Triptorelin Pamoate

The effects of treatment with a bombesin receptor antagonist [D-Tpi6, Leu13 psi (CH2NH) Leu14]BN(6-14)(RC-3095) and the combination of an agonist of luteinizing hormone-releasing hormone [D-Trp6]-LH-RH and somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val- Cys-Trp-NH2 (RC-160) were studied in nude mice bearing xenografts of the hormone-dependent human prostate tumor PC-82. During the 5 weeks of treatment, tumor growth was decreased in all treated groups compared with controls. Bombesin antagonist RC-3095 and the combination of [D-Trp6]-LH-RH and RC-160 caused a greater inhibition of tumor growth than [D-Trp6]-LH-RH or RC-160 alone as based on measurement of tumor volume and percentage change in tumor volume. The largest decrease in tumor weight was also seen in the groups treated with the bombesin antagonist and with the combination of RC-160 and [D-Trp6]-LH-RH. Serum prostatic-specific antigen levels were greatly decreased, and insulin-like growth factor I (IGF-I) as well as growth hormone levels were reduced in all treated groups. Specific binding sites for [D-Trp6]-LH-RH, epidermal growth factor (EGF), IGF-I, and somatostatin (SS-14) were found in the tumor membranes. Receptors for EGF were significantly down-regulated by treatment with the bombesin antagonist or RC-160. Combination of LH-RH agonists with somatostatin analog RC-160 might be considered for improvement of hormonal therapy for prostate cancer. The finding that bombesin antagonist RC-3095 inhibits the growth of PC-82 prostate cancer suggests the merit of further studies to evaluate the possible usefulness of antagonists of bombesin in the management of prostatic carcinoma.

Topics: Amino Acid Sequence; Animals; Antigens, Neoplasm; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Body Weight; Bombesin; Cell Division; Gonadotropin-Releasing Hormone; Hormones; Humans; Insulin-Like Growth Factor I; Kinetics; Male; Mice; Mice, Nude; Molecular Sequence Data; Organ Size; Peptide Fragments; Prostate-Specific Antigen; Prostatic Neoplasms; Somatostatin; Transplantation, Heterologous; Triptorelin Pamoate

Cytotoxic luteinizing hormone-releasing hormone (LH-RH) analogs, AJ-004 (agonist [D-Lys6]LH-RH linked to methotrexate (MTX)), T-98 ([D-Lys6]LH-RH coupled to glutaryl-2-(hydroxymethyl)anthraquinone) (G-HMAQ) and T-121/B (antagonist containing two residues of G-HMAQ) were tested in female BDF1 mice bearing MXT ((3.2)/Ovex) estrogen-independent mammary tumors. All three cytotoxic LH-RH analogs, administered from Alzet Osmotic Minipumps for 3 weeks, produced a significant inhibition of tumor growth. The effects of T-98 and T-121/B were superior to those obtained by treatment with equimolar doses of cytotoxic moiety anthraquinone or the LH-RH carrier alone. We assume that cytotoxic LH-RH analogs have a combined hormonal and cytotoxic activity with a reduced toxicity after administration in vivo. This is the first demonstration of in vivo tumor inhibition by targeted LH-RH analogs bearing cytotoxic radicals.

Topics: Amino Acid Sequence; Animals; Anthraquinones; Binding Sites; Body Weight; Cell Division; Female; Gonadotropin-Releasing Hormone; Growth Hormone; Kinetics; Luteinizing Hormone; Mammary Neoplasms, Experimental; Methotrexate; Mice; Mice, Inbred Strains; Molecular Sequence Data; Ovary; Receptors, LH; Triptorelin Pamoate; Uterus

The effects of a long-acting gonadotropin-releasing hormone (GnRH) agonist, [D-Trp6]-GnRH (GnRH-A) on developmental profiles of plasma luteinizing hormone (LH), follicle stimulation hormone (FSH) and testosterone (T), and pituitary responsiveness to exogenous GnRH were studied in male Dutch Landrace x Large White crossbred pigs from 1 to 30 wk of age. Group 1 control animals (control; n = 12) were injected subcutaneously in the neck with vehicle at 1 and 16 wk of age. Group 2 animals (early treatment; n = 10) were injected with 600 micrograms [D-Trp6]-GnRH at 1 wk and with vehicle at 16 wk. Group 3 animals (late treatment; n = 8) were injected with vehicle and 3 mg GnRH-A at 1 and 16 wk, respectively. Group 4 animals (early plus late treatment; n = 9) were injected at both 1 and 16 wk with GnRH-A. Blood was collected by brachiocephalic puncture at weekly or biweekly intervals, and through brachiocephalic cannulae, to determine longitudinal profiles of LH, FSH and T, and plasma gonadotropin responses to intravenous injection of GnRH (0.1 microgram/kg), respectively. In control animals, LH and FSH declined over the first 5 wk of postnatal life and peaked again at 10-14 wk. Levels of both hormones were basal from 18 to 30 wk. Plasma T was high in the first week, declined progressively over the next few weeks and remained low until 24 wk when a transient increment was noted. The LH and FSH responses to acute GnRH stimulation were similar at 7 and 14 wk and declined significantly at 23 wk of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Body Weight; Follicle Stimulating Hormone; Genitalia, Male; Gonadotropin-Releasing Hormone; Hormones; Luteinizing Hormone; Male; Organ Size; Sexual Maturation; Swine; Testosterone; Triptorelin Pamoate

To study the efficacy of long-term buserelin acetate infusion to desensitize pituitary and block testicular function in adult male monkeys (Macaca radiata).. Proven fertile male monkeys exhibiting normal testicular function.. Each of the control (n = 5) and experimental monkeys (n = 10) received a fresh miniosmotic pump every 21 days, whereas pumps in controls delivered vehicle of experimentals released 50 micrograms buserelin acetate every 24 hours. On day 170 (renewed every 60 days) a silastic capsule containing crystalline testosterone (T) was implanted in the experimental monkeys. At the end of 3 years, treatment was stopped, and recovery of testicular function and fertility monitored.. (1) Treatment resulted in marked reduction of nocturnal but not basal serum T; (2) the pituitary remained desensitized to buserelin acetate throughout the 3-year period; (3) animals were largely azoospermic with occasional oligospermia exhibited by two monkeys; and (4) withdrawal of treatment restored testicular function, with 70% of animals regaining fertility.. Long-term infertility (but restorable) can be induced in male monkeys by constant infusion of buserelin acetate and T.

Topics: Animals; Body Weight; Delayed-Action Preparations; Drug Implants; Gonadotropin-Releasing Hormone; Infusions, Intravenous; Macaca radiata; Male; Organ Size; Reference Values; Sperm Count; Testis; Testosterone; Triptorelin Pamoate

The LH-RH analog LH-RH-A (des-Gly10,[D-Trp6]-LH-RH ethylamide) was administered in pharmacological doses (20 micrograms/kg, sc) to adult male cats for 15 days and its effect on testis and adrenal function was determined. Daily administration of the analog promoted a 3-fold increase in plasma testosterone levels after 7 days, indicating a stimulatory effect of LH-RH-A (mean +/- SD for 6 treated cats, 1.88 +/- 0.35 vs 0.51 +/- 0.08 ng/ml for 6 control cats). After 15 days the LH-RH-A-treated group exhibited a similar plasma testosterone concentration as the control group (mean +/- SD, 0.96 +/- 0.35 ng/ml vs 0.88 +/- 0.39 ng/ml, respectively), similar testicular and adrenal weights and no significant differences in the spermatogenic process. However, semiquantitative analysis of the zona fasciculata of the adrenals from the LH-RH-A-treated group showed a significant accumulation of a substance not stained by hematoxylin-eosin or Schiff periodic acid (mean +/- SD of index of accumulation was 3.50 +/- 0.4 for treated cats vs 2.20 +/- 0.3 for control cats). The present results show that pharmacological doses of LH-RH-A have an effect on the adrenal cortex of cats without modifying spermatogenesis or plasma testosterone levels.

Topics: Adrenal Cortex; Animals; Body Weight; Cats; Gonadotropin-Releasing Hormone; Male; Organ Size; Spermatogenesis; Testis; Testosterone; Triptorelin Pamoate

Suppression of gonadal sex steroid secretion in children with central precocious puberty (CPP) by LHRH analogs affords an opportunity to study sex steroid modulation of GH and somatomedin-C (Sm-C) secretion and to examine the role of GH and Sm-C in pubertal and prepubertal statural growth. Nocturnal serum GH and plasma Sm-C levels were measured in 10 preadrenarchal girls [mean age, 3.0 +/- 0.6] ( +/- SEM) yr with CPP before and during 2 yr of LHRH analog-induced gonadal suppression. Their mean height velocity, initially 4.6 +/- 0.6 ( +/- SEM) SD above the mean for chronological age, decreased to -0.1 +/- 0.4 SD during 12-24 months of ovarian suppression (P less than 0.00005). The mean peak nocturnal plasma GH level was 22.5 +/- 5.4 ( +/- SEM) micrograms/L during puberty, and it decreased to 10.2 +/- 2.1 micrograms/L after 3 months of suppression of gonadarche. This decrease persisted throughout the 2 yr of gonadal suppression (P less than 0.05). The reduction in GH secretion was accompanied by a decrease in mean plasma Sm-C levels from 3.5 +/- 0.7 to 1.5 +/- 0.2 U/mL after 3 months of suppression of gonadal sex steroids, which persisted during 2 yr of gonadal suppression (P less than 0.01). Suppression of ovarian function in girls with CPP results in decreased height velocity. This slowing of growth occurs in association with decreased nocturnal serum GH and plasma Sm-C levels, suggesting that acceleration of growth during puberty is partially mediated by sex steroid-induced augmentation of GH secretion.

Topics: Age Determination by Skeleton; Body Height; Body Weight; Bone Development; Child, Preschool; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Growth Hormone; Humans; Infant; Insulin-Like Growth Factor I; Ovary; Pituitary Gland; Puberty, Precocious; Somatomedins; Triptorelin Pamoate

To test the hypothesis that the functional state of hypothalamic LHRH neurons and pituitary gonadotrophs might alter their radiosensitivity, we determined the experimental conditions under which the gonadotropin response to castration could be impaired by a single dose of cranial irradiation. Single doses of cranial irradiation greater than 2000 rads were lethal to unshielded rats. Shielding of the oropharynx and esophagus allowed the animals to survive doses up to 5000 rads. Doses between 2000 and 5000 rads had no effect on basal gonadotropin levels for as long as 3 months after irradiation. Irradiation caused a dose- and time-dependent impairment, however, in the gonadotropin response to castration. Impairment of the gonadotropin levels of castrate animals occurred in animals that were irradiated either before or after castration. However, rats irradiated in the castrate state showed a decreased susceptibility to irradiation damage. Additionally, stimulation of the pituitary by LHRH agonist (LHRHa) 3 h before irradiation significantly reduced the impairment of gonadotropin secretion 12-20 weeks after irradiation (P less than 0.05). Thus, increased functional activity of the rat hypothalamus or pituitary at the time of irradiation, induced by either castration or acute LHRHa administration, was associated with some protection against the gonadotropin-lowering effect of irradiation. Based upon these data, we hypothesize that stimulation of gonadotropin secretion at the time of therapeutic cranial irradiation in humans might protect against subsequent impairment of gonadotropin secretion.

Topics: Animals; Body Weight; Dose-Response Relationship, Radiation; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hypothalamus; Luteinizing Hormone; Male; Orchiectomy; Pituitary Gland; Rats; Rats, Inbred Strains; Testosterone; Thyroid Gland; Thyroxine; Triptorelin Pamoate

The therapy for the treatment of prostate cancer and other sex-steroid-dependent tumors based on agonists of LH-RH has been made more practical and efficacious by the development of a long-acting formulation of microcapsules of D-Trp-6-LH-RH for controlled release. Antiandrogens, which neutralize the effect of endogenous androgens, have been used also in the management of prostate cancer in man. The effects of a simultaneous administration of the antiandrogen flutamide and microcapsules of the agonist D-Trp-6-LH-RH were studied in the Dunning R-3327H rat prostate adenocarcinoma model to determine whether the combination of these two drugs might inhibit tumor growth more effectively than single agents. Microcapsules of D-Trp-6-LH-RH, calculated to release a controlled dose of 25 micrograms/day for a period of 30 days were injected intramuscularly once a month. Flutamide was administered SC at a daily dose of 25 mg/kg. The therapy was started 100 days after the tumor transplantation and continued for 60 days. Tumor weights and volumes were significantly reduced in rats treated with microcapsules or flutamide alone, but the former drug inhibited tumor growth more than the latter. The combined treatment of flutamide and microcapsules significantly decreased tumor weight and volume, but did not exert a synergistic effect on tumor growth, the reduction being smaller for the combination than for the microcapsules alone. There was a significant elevation of serum testosterone, LH, and prolactin in rats treated with flutamide. On the other hand, in rats given microcapsules of D-Trp-6-LH-RH, testosterone fell to castration levels within 7 days and remained at nondetectable values, serum LH and prolactin levels being also suppressed in this group. The combined administration of microcapsules and flutamide also significantly decreased serum testosterone to nondetectable levels by day 7 and suppressed serum LH and prolactin. Our findings raise doubts of whether the daily administration of the combination of LH-RH agonist with an antiandrogen offers an advantage over the use of microcapsules of an agonist like D-Trp-6-LH-RH alone in the treatment of prostatic carcinoma.

Topics: Anilides; Animals; Body Weight; Cell Line; Drug Therapy, Combination; Flutamide; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Male; Neoplasms, Hormone-Dependent; Organ Size; Prolactin; Prostate; Prostatic Neoplasms; Rats; Testis; Testosterone; Triptorelin Pamoate

The aim of this study was to evaluate the effect of the agonistic LRH analogue (D-Trp6-LRH) on LH, FSH and prolactin secretion, and its possible efficacy in female patients with anorexia nervosa. The study included 18 female patients with anorexia nervosa and 7 healthy women in the same age group. The patients with anorexia nervosa were divided into two groups of 9 women each. The first group consisted of patients in the weight loss phase of the disorder and the second of 9 women who had achieved normal body weight. Additionally, in 6 women with anorexia nervosa serum LH concentration was determined in response to native LRH before and 14 days after the treatment with D-Trp6-LRH. Serum LH, FSH, prolactin concentrations were determined before and 5, 10, 24 and 48 h after administration of D-Trp6-LRH in a dose of 5 micrograms. The serum LH response to D-Trp6-LRH in the second group did not differ from that of the control group. However, in women with anorexia nervosa in the weight loss phase, LH release in response to administration of the analogue was significantly lower. FSH release after LRH analogue administration in both groups of patients with anorexia nervosa did not differ from that in the control group. The increased LH secretion in response to native LRH after treatment indicates that D-Trp6-LRH in low doses did not inhibit pituitary responsiveness. A dose of 5 micrograms of D-Trp6-LRH was administered in a therapeutic regimen every 48 h from 1 to 3 months to 7 of 9 patients with anorexia nervosa who exhibited amenorrhoea in spite of normalization of body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Anorexia Nervosa; Body Weight; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Menstruation; Prolactin; Triptorelin Pamoate

D-Tryptophan-6-luteinizing hormone-releasing hormone (D-Trp6-LH-RH) applied from day -8 to day +15 before and after administration of the nitrosourea analog, N,N'-bis[N-(2-chloroethyl)-N-nitrosocarbamoyl]cysteamine (CNCC), favored bone marrow restoration, as independently evaluated by 3 observers in a double-blind fashion.

Topics: Animals; Body Weight; Bone Marrow; Bone Marrow Diseases; Double-Blind Method; Gonadotropin-Releasing Hormone; Hematopoietic Stem Cells; Luteolytic Agents; Male; Mice; Nitrosourea Compounds; Triptorelin Pamoate

We have investigated the effect of the D-Trp6 analogue of luteinizing hormone-releasing hormone (LH-RH), a superactive analogue of LH-RH, on the growth of two different models of prostate tumors in rats. Chronic administration of D-Trp6-LH-RH in a dose of 25 micrograms/day for 14-21 days significantly inhibited the growth of the chemically induced squamous cell carcinoma 11095 in Fisher 344 male rats. The weights of the ventral prostate and testes were also significantly reduced by treatment with this analogue. After 21 days of treatment, the animals no longer showed increases in serum luteinizing hormone and follicle-stimulating hormone levels in response to D-Trp6-LH-RH. Treatment of male Copenhagen F-1 rats bearing the Dunning 3327 prostate adenocarcinoma with 25 micrograms of D-Trp6-LH-RH per day for 42 days decreased the weights of both the ventral prostate and testes but had no effect on the weight of the anterior pituitary gland. The percentage increase in tumor volume was decreased to one-third and the actual tumor weight was decreased by 58% compared to untreated controls. The tumor doubling time was more than 4 times longer in rats receiving D-Trp6-LH-RH than in controls. Serum levels of luteinizing hormone and follicle-stimulating hormone were significantly decreased in rats receiving this analogue. In both Fisher 344 and Copenhagen F-1 rats, serum prolactin and testosterone levels were significantly decreased after treatment with D-Trp6-LH-RH, whereas progesterone levels were increased.

Topics: Animals; Body Weight; Follicle Stimulating Hormone; Genitalia, Male; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Male; Neoplasms, Experimental; Organ Size; Progesterone; Prolactin; Prostatic Neoplasms; Rats; Rats, Inbred F344; Testosterone; Triptorelin Pamoate

Subcutaneous implantation of pelleted (DTrp6-Des Gly10-ProNH29)-luteinizing hormone-releasing hormone in 3 heifers (at a total dose of approx 5 microgram/0.45 kg of body weight) shortly after ovulation did not affect the ongoing luteal phase, but prevented the next expected estrus and ovulation. The effect was reversible and estrus was reestablished 16 and 19 days after pellet removal. The subsequent luteal phase concentrations of plasma progesterone appeared to be below normal concentrations. In a 2nd study, 25 heifers were implanted subcutaneously twice, 56 days apart, at random stages of the cycle. The mean number of estrous episodes over the 112 days of observation was decreased from 5.56 in controls (n = 25) to 1.12 in treated (n = 25) heifers. This suppression of estrus was not associated with change in live weight gain or food intake.

Topics: Animal Feed; Animals; Body Weight; Cattle; Delayed-Action Preparations; Estrus; Female; Gonadotropin-Releasing Hormone; Pregnancy; Progesterone; Triptorelin Pamoate