Leuprolide

To compare goserelin and leuprolide given before hysterectomy for symptomatic large fibroid uteri. A randomized study of 66 premenopausal women with fibroid uteri at least 14 weeks of gestation in a gravid uterus. Women were randomized to receive either subcutaneous depot 3.6 mg goserelin or 3.75 mg leuprolide every 4 weeks for a total of 3 doses. Hysterectomy was performed within 1 month of the last dose. A total of 34 women randomized to the goserelin group and 31 women to the leuprolide group were available for analysis. Preoperative hemoglobin level (P=0.89), operative blood loss (P=0.72), and operating time (P=0.39) were not different between the 2 groups. Postoperative hemoglobin was higher in the leuprolide group (P=0.003), but blood transfusion requirement was not different between the groups (P=1.0). Other outcomes and side effects of the drugs were similar. Goserelin and leuprolide administered before hysterectomy for uterine fibroids have similar perioperative outcomes.

The purpose of this study was to develop thiolated nanoparticles to enhance the bioavailability for the nasal application of leuprolide. Thiolated chitosan-thioglycolic acid (chitosan-TGA) and unmodified chitosan nanoparticles (NPs) were developed via ionic gelation with tripolyphosphate (TPP). Leuprolide was incorporated during the formulation process of NPs. The thiolated (chitosan-TGA) NPs had a mean size of 252 ± 82 nm, a zeta potential of +10.9 ± 4 mV, and payload of leuprolide was 12 ± 2.8. Sustained release of leuprolide from thiolated NPs was demonstrated over 6h, which might be attributed to inter- and/or intramolecular disulfide formation within the NPs network. Ciliary beat frequency (CBF) study demonstrated that thiolated NPs can be considered as suitable additives for nasal drug delivery systems. Compared to leuprolide solution, unmodified NPs and thiolated NPs provoked increased leuprolide transport through porcine nasal mucosa by 2.0 and 5.2 folds, respectively. The r...

ObjectiveSpinal and bulbar muscular atrophy (SBMA) is a hereditary motor neuron disease caused by the expansion of a polyglutamine tract in the androgen receptor (AR). Animal studies have shown that the pathogenesis of SBMA is dependent on serum testosterone level. This study is aimed at evaluating the efficacy and safety of androgen deprivation by leuprorelin acetate in patients with SBMA.Spinal and bulbar muscular atrophy (SBMA) is a hereditary motor neuron disease caused by the expansion of a polyglutamine tract in the androgen receptor (AR). Animal studies have shown that the pathogenesis of SBMA is dependent on serum testosterone level. This study is aimed at evaluating the efficacy and safety of androgen deprivation by leuprorelin acetate in patients with SBMA.MethodsFifty SBMA patients underwent subcutaneous injections of leuprorelin acetate or placebo in a randomized, placebo-controlled trial for 48 weeks, followed by an open-label trial for an additional 96 weeks, in which 19 patients of the leuprorelin group and 15 of the placebo group received leuprorelin acetate. The patients who did not participate in the open-label trial were also followed up for the 96-week period (UMIN000000474).Fifty SBMA patients underwent subcutaneous injections of leuprorelin acetate or placebo in a randomized, placebo-controlled trial for 48 weeks, followed by an open-label trial for an additional 96 weeks, in which 19 patients of the leuprorelin group and 15 of the placebo group received leuprorelin acetate. The patients who did not participate in the open-label trial were also followed up for the 96-week period (UMIN000000474).ResultsLeuprorelin acetate significantly extended the duration of cricopharyngeal opening in videofluorography and decreased mutant AR accumulation in scrotal skin biopsy. The patients treated with leuprorelin acetate for 144 weeks exhibited significantly greater functional scores and better swallowing parameters than those who received placebo. Autopsy of one patient who received leuprorelin acetate for 118 weeks suggested that androgen deprivation inhibits the nuclear accumulation or stabilization, or both, of mutant AR in the motor neurons of the spinal cord and brainstem.Leuprorelin acetate significantly extended the duration of cricopharyngeal opening in videofluorography and decreased mutant AR accumulation in scrotal skin biopsy. The patients treated with leuprorelin acetate for 144 weeks exhibited significantly greater functional scores and better swallowing parameters than those who received placebo. Autopsy of one patient who received leuprorelin acetate for 118 weeks suggested that androgen deprivation inhibits the nuclear accumulation or stabilization, or both, of mutant AR in the motor neurons of the spinal cord and brainstem.InterpretationThese observations suggest that administration of leuprorelin acetate suppresses the deterioration of neuromuscular impairment in SBMA by inhibiting the toxic accumulation of mutant AR. The results of this phase 2 trial support the start of large-scale clinical trials of androgen deprivation for SBMA. Ann Neurol 2009;65:140–150These observations suggest that administration of leuprorelin acetate suppresses the deterioration of neuromuscular impairment in SBMA by inhibiting the toxic accumulation of mutant AR. The results of this phase 2 trial support the start of large-scale clinical trials of androgen deprivation for SBMA. Ann Neurol 2009;65:140–150

Surveys of sexual behavior in autism suggest a variety of behavioral expression. However, the course of sexual development in autism is unplotted, leaving questions about the normalcy of specific behaviors. Even less is known about deviations of sexual development and the incidence of paraphilias in this population. We explore the problems of definition of sexual behaviors and describe a case report that highlights the difficulties of management. An application of a testosterone-suppressing medication and its effect on sexual behavior are reported. After failure of behavioral and educational programs, leuprolide, an injectable antiandrogen, resulted in suppression of behaviors and retention of the participants' community placement. Follow-up for almost 3 years shows no abnormal physical effects. Dosage has been tapered over that period to a low but effective dose. Directions for research are discussed.

Surveys of sexual behavior in autism suggest a variety of behavioral expression. However, the course of sexual development in autism is unplotted, leaving questions about the normalcy of specific behaviors. Even less is known about deviations of sexual development and the incidence of paraphilias in this population. We explore the problems of definition of sexual behaviors and describe a case

To evaluate the ovarian function during early infancy in daughters of women with polycystic ovary syndrome (PCOS) treated with metformin throughout pregnancy (PCOSd+M), as a means to reduce androgen and insulin levels, compared with daughters of nontreated PCOS women (PCOSd−M) and daughters of women who belong to a healthy comparison group (HCd).Descriptive and analytic study.Unit of endocrinology and reproductive medicine.Fifteen PCOSd+M, 23 PCOSd−M, and 35 HCd were studied at 2–3 months of age.A GnRH analogue test was performed with determinations of gonadotropins, sex steroids, SHBG, and anti-Müllerian hormone (AMH).Differences in AMH levels between PCOSd+M, PCOSd−M and HCd.AMH and peak E2 concentrations were significantly higher in PCOSd−M compared with HCd, whereas PCOSd+M exhibited AMH concentrations and peak E2 levels similar to those observed in HCd.The improvement of the altered endocrine-metabolic environment of PCOS mothers reduces AMH levels in their daughters, which might reflect a decrease in their follicular mass.

The results obtained with a protocol consisting of ovarian stimulation with low doses of highly purified FSH (FSH HP), administration of a GnRH analogue to induce an endogenous surge of gonadotropins, and IUI were evaluated. These results were compared with those seen with similar FSH stimulation and hCG administration followed by IUI. Three hundred sixty-four patients scheduled for IUI, after inclusion in a total of 345 FSH HP/GnRH-stimulated cycles and 416 FSH HP/HCG-stimulated cycles, were studied. The stimulation protocol consisted of daily subcutaneous injection of 75 IU of FSH HP from day 3 or 5 of the cycle, depending on the duration of the spontaneous cycle. hCG was administered on days 0, +2, and +5 to support the luteal phase. Monitoring was conducted using circulating estradiol levels and vaginal ultrasonography. Administration of two s.c. doses of leuprolide acetate (LA) or 7500 IU of i.m. hCG when at least one 18-mm-diameter follicle was seen and estradiol levels reache...

The majority of patients with ovarian cancer are not cured by first-line treatment. Until now, no study could demonstrate any substantial benefit when exposing ovarian cancer patients to second-line chemotherapy. However, most treatment regimens induce toxicity, thus negatively influencing the quality of rather limited life spans. Here we evaluate whether a second-line chemotherapy can offer any benefit compared with a less toxic hormonal treatment. Patients with ovarian cancer progressing during platinum-paclitaxel containing first-line therapy or experiencing relapse within 6 months were eligible. Patients were stratified for response to primary treatment (progression versus no change/response), and measurable versus non-measurable disease. Treatment consisted of either treosulfan 7 g/m5 infused over 30 min or leuprorelin 3.75 mg injected subcutaneously or intramuscularly. Both regimens were repeated every 4 weeks. This study began in late 1996, and after 2.5 years accrual an inte...

Biomarkers that predict musculoskeletal response to anabolic therapies should expedite drug development. During collagen synthesis in soft lean tissue, N-terminal propeptide of type III procollagen (P3NP) is released into circulation. We investigated P3NP as a biomarker of lean body mass (LBM) and muscle strength gains in response to testosterone and GH. Community-dwelling older men received GnRH agonist plus 5 or 10 g testosterone gel plus 0, 3, or 5 microg recombinant human GH daily. P3NP levels were measured at baseline and wk 4, 8, 12, and 16. LBM and appendicular skeletal muscle mass (ASM) were measured by dual-energy x-ray absorptiometry. One hundred twelve men completed treatment; 106 underwent serum P3NP measurements. P3NP levels were higher at wk 4 than baseline (6.61 +/- 2.14 vs. 4.51 +/- 1.05, P < 0.0001) and reached plateau by wk 4 in men receiving testosterone alone. However, wk 8 P3NP levels were higher than wk 4 levels in men receiving testosterone plus recombinant human GH. Increases in P3NP from baseline to wk 4 and 16 were significantly associated with gains in LBM (r = 0.26, P = 0.007; r = 0.53, P < 0.001) and ASM (r = 0.17, P = 0.07; r = 0.40, P < 0.0001). Importantly, for participants receiving only testosterone, P3NP increases at wk 4 and 16 were related to muscle strength gains (r = 0.20, P = 0.056 and r = 0.36, P = 0.04). In stepwise regression, change in P3NP explained 28 and 30% of the change in ASM and LBM, respectively, whereas change in testosterone but not IGF-I and age provided only small improvements in the models. Early changes in serum P3NP levels are associated with subsequent changes in LBM and ASM during testosterone and GH administration. Serum P3NP may be a useful early predictive biomarker of anabolic response to GH and testosterone.

This review provides an update on leuprorelin acetate, the world's most widely prescribed depot luteinising hormone-releasing hormone analogue. Leuprorelin acetate has been in clinical use in the palliative treatment of prostate cancer for more than 20 years, but advances continue to be made in terms of convenience and flexibility of administration, and in the incorporation of leuprorelin acetate into novel treatment regimens. The drug is administered in the form of a depot injection containing leuprorelin acetate microspheres, and is at least as effective in suppressing testosterone secretion as orchiectomy. In patients with prostate cancer, serum testosterone levels are reduced to castrate levels (< or = 50 ng/dl) within 2-3 weeks of the first one-month depot injection of 3.75 mg or three-month depot injection of 11.25 mg. Both the one-month and three-month formulations are effective in delaying tumour progression and alleviating symptoms of locally advanced and metastatic ...