goserelin and Polycystic-Ovary-Syndrome

Goserelin is a synthetic analogue of gonadotrophin-releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH); or gonadorelin] which stimulates gonadotrophin and sex hormone release in the short term, and then causes suppression with continued administration. Goserelin is given as a subcutaneous biodegradable depot incorporating 3.6 mg of the drug, which is released continuously at an average rate of 120 micrograms/day over 4 weeks. Monthly goserelin depot therapy produces partial disease remission or stabilisation in about 75% of men with previously untreated prostatic cancer, a rate equivalent to that achieved with orchidectomy or diethylstilbestrol (stilboestrol). The response to goserelin is more rapid than to diethylstilbestrol, and goserelin is better tolerated. About 30 to 45% of premenopausal women with breast cancer responded to goserelin using objective assessment criteria, suggesting comparability to ovariectomy. In benign hormone-dependent conditions, preoperative goserelin aids surgical removal of uterine leiomyoma (fibroids) and reduces blood loss, and 6 months of therapy relieves the signs and symptoms of endometriosis. The elevation in testosterone at the beginning of goserelin therapy can result in disease 'flare' in men with prostate cancer, and sex steroid suppression with continued treatment results in hot flushes and loss of libido in most patients. Thus, goserelin is an effective alternative to surgery or estrogen therapy in prostatic cancer palliation, and possibly to ovariectomy in premenopausal breast cancer. Other gynaecological conditions reliant on the pituitary-gonadal axis also appear amenable to hormone manipulation with goserelin.

Topics: Animals; Breast Neoplasms; Buserelin; Drug Evaluation; Endometriosis; Female; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Gonadotropins; Goserelin; Humans; Leiomyoma; Male; Menstruation Disturbances; Polycystic Ovary Syndrome; Prostatic Neoplasms; Uterine Neoplasms

In this study, our aim was to compare the effects of metformin and gonadotropin releasing hormone (GnRH) analogues in clinical and hormonal parameters in women with polycystic ovary syndrome (PCOS). There were 50 women with PCOS who were included in our study and they were divided into two groups. In this randomized trial, metformin (850 mg, two times per day) was administered to the first group and GnRH analogue (goserelin 3.6 mg, every 28 days) was given to the second group for 3 months. Because of the previous treatments, PCOS patients served as their own controls. The results of 42 women who completed the study were evaluated. Insulin resistance was not ascertained in patients. Metformin treatment resulted in a significant decline in mean body mass index, body weight, circumferences of waist and hip and total hirsutismus score. There was a significant decrease in luteinizing hormone (LH) levels and a significant increase in follicle stimulating hormone (FSH), progesterone, and sex hormone binding globulin (SHBG) concentrations. No changes in fasting glucose and insulin levels were observed. The GnRH analogue resulted in a significant increase in FSH and SHBG levels and a significant decrease in LH, total testosterone, dehydroepiandrosterone sulfate (DHEAS) levels and LH to FSH ratio and an improvement in hirsutism scores. Metformin and GnRH analogues had effects upon the abnormal steroid-gonadotropin metabolism and the clinical findings of hyperandrogenism with different mechanisms.

Topics: Adult; Female; Gonadotropin-Releasing Hormone; Goserelin; Hormones; Humans; Hypoglycemic Agents; Metformin; Polycystic Ovary Syndrome

Thirty-two women with polycystic ovary syndrome (PCOS) were allocated to two antiandrogen treatment regimens; 28 women completed the trial. Twenty women were treated with ethinyloestradiol and cyproterone acetate (EO-CA) cyclically for 6 months and eight women were treated with the gonadotrophin releasing hormone (GnRH) analogue, goserelin for 6 months. Effects on hirsutism, insulin sensitivity (estimated by glucose clamp technique), blood lipids and hormones were measured. Women treated with EO-CA showed a reduction in hirsutism (P <0.05), and decreased serum androgen concentrations (P <0.001) as well as reduced insulin sensitivity (P <0.05). In women treated with goserelin, serum androgen concentrations also decreased (P <0.001), but there was no significant reduction of hirsutism. This group, however, showed an improved insulin sensitivity (P <0.05) despite an unchanged body mass index. Bone mineral density was unaltered in both treatment groups. The reduction in androgen concentrations caused by EO-CA was not paralleled by increased insulin sensitivity, most probably due to the effect of ethinyloestradiol per se. In contrast, the reduction in androgen concentrations by goserelin was accompanied by an improved insulin sensitivity.

Topics: Adult; Androgen Antagonists; Androgens; Cyproterone Acetate; Estradiol Congeners; Ethinyl Estradiol; Female; Goserelin; Hirsutism; Humans; Insulin Resistance; Lipids; Polycystic Ovary Syndrome

To study the effects of laparoscopic ovarian cauterization and combination of long-acting GnRH agonist (GnRH-a) and oral contraceptive (OC) therapy on endocrine changes in women with clomiphene citrate (CC)- resistant polycystic ovary disease (PCOD).. Prospective, randomized.. University-based infertility clinic.. Seventeen women with CC-resistant PCOD were included randomly in the study to either laparoscopic ovarian cautery or GnRH-a and OC therapy for 3 months.. Serum concentrations of LH, FSH, androstenedione (A), T, and sex hormone-binding globulin (SHBG) were determined before each therapeutic approach and during the follicular phase of first menstrual cycle after the cessation of each treatment.. The mean serum concentrations and the clinical profiles were similar in both groups. Both groups showed significant changes in LH, FSH, A, T, and SHBG compared with pretreatment levels. There were no significant differences in the final concentrations of LH, FSH, and A between the two study groups after each treatment, whereas T and SHBG levels were significantly different in the goserelin and OC group. The decrease in LH and increase in SHBG serum concentrations were greater in the goserelin and OC-treated women [-59% and + 5.9% versus - 70% and + 13.5%, respectively]. Although the SHBG concentration increased in both groups, the serum SHBG concentration of the goserelin and OC group was significantly higher than the other group.. Both therapeutic modalities revealed similar effects on the endocrine profiles in women with CC-resistant PCOD. Considering the invasiveness, cost, and potential complications of laparoscopic ovarian cauterization, noninvasive medical treatment with GnRH-a and OC combination may be more effective in restoring the optimal follicular environment in women with PCOD.. This paper reports findings from the study of the comparative effects of laparoscopic ovarian cauterization and combined long-acting GnRH agonist (GnRH-a) and oral contraceptive (OC) therapy upon endocrine changes in women with clomiphene citrate (CC)-resistant polycystic ovary disease (PCOD). 17 women with CC-resistant PCOD were included randomly into the prospective study of either laparoscopic ovarian cautery or GnRH-a and OC therapy for three months. Both therapeutic approaches produced similar effects upon the endocrine profiles of women with CC-resistant PCOD, with both groups showing significant changes in LH, FSH, androstenedione, T, and sex hormone binding globulin compared with pretreatment levels. However, given the invasiveness, cost, and potential complications of laparoscopic ovarian cauterization, noninvasive medical treatment with GnRH-a and OC may be the most practical and appropriate approach to restoring the optimal follicular environment in women with PCOD.

Topics: Adult; Androstenedione; Cautery; Contraceptives, Oral; Female; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Ovary; Polycystic Ovary Syndrome; Prospective Studies; Sex Hormone-Binding Globulin; Testosterone

To evaluate the efficacy and tolerability of treatment with goserelin + HMG vs bromocriptine + FSH + HMG in the induction of ovulation in patients with ovarian polycystosis.. A randomized prospective study.. Sterile women with ovarian polycystosis of the first type not responding to clomiphene citrate.. Group A: bomocriptine + FSH + HMG (10 patients); Group B: goserelin depot (Zoladex) + HMG (18 patients).. A greater percentage of ovulations, pregnancies and a higher success rate were obtained in Group B. The percentage of hyperstimulation was similar in both groups; there was a higher percentage of abortion in Group A. Cycle duration and the number of phials of gonadotropin were greater in Group B.. Treatment with bromocriptine + gonadotropin remains the simplest; the treatment protocol based on geserelin depot + gonadotropin proved to be more efficacious.

Topics: Adult; Bromocriptine; Clinical Protocols; Dose-Response Relationship, Drug; Female; Follicle Stimulating Hormone; Goserelin; Humans; Infertility, Female; Menotropins; Ovulation Induction; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Complications; Pregnancy Outcome

Luteinising hormone (LH) is essential for steroidogenesis and folliculogenesis. In hyperandrogenic patients, however, an increased androgen production with the consecutive development of polycystic ovaries is caused by elevated LH levels. Suppression of androgens by the use of a GnRH agonist (a) may be a causal therapeutic approach. Therefore, we initiated a study comparing the combined GnRHa/HMG stimulation with HMG alone in hyperandrogenic patients undergoing in-vitro fertilisation (IVF). Altogether, 62 cycles were treated. Group 1 (n = 33) received a single depot injection of 3.6 mg goserelin on cycle day 22 followed by individualised HMG stimulation 14 days later. Group 2 (n = 29) started with the HMG stimulation on cycle day 3. In group 1, a pregnancy rate per transfer of 36.4% was achieved compared to only 20% in group 2. There was a strikingly lower abortion rate in group 1 that resulted in a significantly higher on going pregnancy rate. The results are in favour of the combined GnRHa/HMG stimulation as a first line therapy for hyperandrogenic IVF patients.

Topics: Adult; Androgens; Delayed-Action Preparations; Drug Administration Schedule; Embryo Transfer; Female; Fertilization in Vitro; Goserelin; Humans; Injections, Subcutaneous; Menotropins; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome

We evaluated the efficacy of ovulation induction using purified FSH in either low dose or conventional dosage in patients with polycystic ovarian syndrome. We assessed whether gonadotrophin measurement by radioimmunoassay or immunoradiometric assay is a better indicator of whether pituitary desensitization with a GnRH agonist (Zoladex) has occurred.. Two different protocols were used. Pituitary desensitization was carried out with a GnRH agonist (Zoladex, ICI Pharmaceuticals UK). The patients were then randomized into one of two treatment groups. Conventional dose protocol: Patients commenced with a daily FSH (Metrodin, Serono Laboratories Ltd, UK) dose of 75 units for at least 7 days. The FSH dose was then increased, if necessary, based on ultrasound scans and plasma oestradiol (E2) levels in 75-unit increments. Low dose protocol: The same protocol was used except that the starting dose of FSH was 37.5 units daily with increments of 37.5 units.. Low dose protocol (six patients, six cycles). There was a high incidence of multiple follicular development (10.3 +/- 5.6 (+/- SD) follicles, 5.0 +/- 3.8 follicles > 14 mm in diameter). Three cycles resulted in ovulation, one was anovulatory and two patients underwent gamete intrafallopian transfer due to multiple follicular development. Conventional dose protocol (seven patients, eight cycles). Again there was multiple follicular development (10.1 +/- 8.6 follicles, 2.0 +/- 2.3 > 14 mm). Three cycles were ovulatory, one anovulatory, three abandoned due to multiple follicular development and one underwent gamete intrafallopian transfer with the development of severe hyperstimulation necessitating steroid therapy. There was no difference between the two protocols in the number of days of FSH administration (low dose protocol 26 +/- 6.5, conventional dose protocol 23 +/- 8.1 days), the total number of units of FSH given per patient was 2844 +/- 1816 vs 2635 +/- 1726. The peak E2 level (pmol/l) during FSH treatment was 3193 +/- 662 vs 2389 +/- 3099 and the rate of increase in the FSH dose in ampoules of Metrodin per day was 0.058 +/- 0.03 vs 0.057 +/- 0.03. All patients were 'downregulated' (E2 < 70 pmol/l) prior to ovulation induction. However, gonadotrophin levels (IU/l) were 4.3 +/- 1.5 (LH) and 2.8 +/- 1.2 (FSH) by radioimmunoassay and LH was unchanged throughout FSH treatment whereas LH measured by immunoradiometric assay was < 1.0 IU/l prior to ovulation induction and remained so throughout. The mean LH radioimmunoassay to immunoradiometric assay ratio was 6.2 +/- 2.1.. We conclude that regardless of the starting dose the use of pure FSH in patients with polycystic ovarian syndrome whose LH has been completely down regulated may be associated with multiple follicular development and a poor outcome. LH measured by radioimmunoassay is not a good indicator of whether pituitary densensitization has occurred but LH measured by immunoradiometric assay appears to be. These results strongly suggest that a basic minimum amount of LH is necessary for normal ovulatory development.

Topics: Adult; Drug Administration Schedule; Female; Follicle Stimulating Hormone; Goserelin; Humans; Immunoradiometric Assay; Luteinizing Hormone; Ovulation Induction; Pituitary Gland; Polycystic Ovary Syndrome; Secretory Rate

Androgens are suggested to interact with leptin production and with insulin sensitivity in both polycystic ovary syndrome (PCOS) and obesity. The aim of the study was to follow these interactions along with two forms of antiandrogen treatment. Twenty women with PCOS were treated with ethinylestradiol and high dose of cyproteroneacetate (EE-CA) and 8 with the gonadotrophin-releasing hormone (GnRH) analogue goserelin for 6 months. The patients were divided into a low and a high body weight group and compared with a group of overweight women without PCOS. Both treatments resulted in a significant reduction of free testosterone but the concentration of leptin remained unchanged. EECA treatment resulted in deterioration and GnRH in improvement of insulin sensitivity. Serum leptin correlated only with body weight and body fat. It is concluded that leptin levels do not adequately reflect changes in insulin sensitivity or androgen levels after short-term antiandrogen or antigonadotropin treatment.

Topics: Adipose Tissue; Adult; Androgen Antagonists; Apolipoproteins A; Apolipoproteins B; Blood Glucose; Body Composition; Body Constitution; Body Mass Index; Body Weight; C-Peptide; Cyproterone Acetate; Dehydroepiandrosterone Sulfate; Ethinyl Estradiol; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Insulin; Insulin Resistance; Leptin; Lipoprotein(a); Obesity; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin; Testosterone; Triglycerides

Topics: Adrenal Hyperplasia, Congenital; Alopecia; Androstenedione; Dehydroepiandrosterone Sulfate; Dexamethasone; Diagnosis, Differential; Female; Gonadotropin-Releasing Hormone; Goserelin; Hirsutism; Humans; Hydrocortisone; Middle Aged; Polycystic Ovary Syndrome; Testosterone; Treatment Outcome

To investigate whether endogenous dopaminergic activity is impaired in polycystic ovary syndrome (PCOS)-affected women and is normalized by medical ovariectomy.. Women with PCOS untreated (n = 23) and treated for 3 months with GnRH analogue (GnRH-a) administration (n = 10) and normal cycling young women (n = 23) as controls.. Acute blockade of dopaminergic receptors by the IV administration of 5 mg of the dopaminergic receptor blocking agent sulpiride (sulpiride test) was performed 3 to 7 days after the initiation of spontaneous menses in cycling women or medroxyprogesterone acetate-induced menses in PCOS women. In PCOS women treated with GnRH-a administration (goserelin depot, 3.6 mg SC every 28 days), the sulpiride test was repeated 10 to 15 days after the third GnRH-a administration.. Basal PRL levels and PRL increase induced by sulpiride.. Basal PRL levels and the PRL response to sulpiride were increased in women with PCOS. In women with PCOS medical ovariectomy induced by GnRH-a administration reversed to normal both basal and sulpiride-stimulated PRL levels.. In women with PCOS the abnormal regulation of PRL and presumably of hypothalamic neurotransmitters controlling PRL secretion is not a primary alteration but it is likely dependent on abnormal ovarian functionality.

Topics: Delayed-Action Preparations; Dopamine; Dopamine Antagonists; Estradiol; Female; Goserelin; Humans; Medroxyprogesterone Acetate; Ovary; Polycystic Ovary Syndrome; Prolactin; Sulpiride

We know that there is a wide range of clinical applications for GnRH analogues in the field of benign gynaecological disorders. As we understand more of the physiology and mechanism of these GnRH agonists, and there appear more varied and perhaps efficient delivery systems, and antagonists become available, it may be possible to develop a graded approach in suppression of the hypothalamic pituitary axis. The true potential of these agents is then yet to be fully realized. There can be no doubt they are going to influence practice dramatically over the next decade. The potency of these agents, perhaps specifically their effects of oestrogen deficiency and calcium bone metabolism, suggests that limitation of duration of use and timing of recurrent administration to individuals is likely to be necessary.

Topics: Buserelin; Danazol; Endometriosis; Estradiol; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leiomyoma; Nafarelin; Osteolysis; Polycystic Ovary Syndrome; Uterine Neoplasms