leuprolide and deslorelin

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

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 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

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

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

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