ay-25-205 and Polycystic-Ovary-Syndrome

A gonadotrophin-releasing hormone (GnRH) analogue, D-Ser[TBU]LRH-EA10, (GnRH-A), at a dose of 200 micrograms was given daily for 2 months to 6 women with polycystic ovarian disease (PCO). Prior to therapy the patients presented elevated LH, testosterone (T), oestrone (E1) and dihydrotestosterone (DHT) in the circulation. In response to GnRH-A, these subjects exhibited a marked decrease in circulating T, DHT and androstenedione (A) levels as measured 24 h after GnRH-A injection, by 4 weeks and onwards (P less than 0.05). After 2 weeks of daily administration, the serum LH profile, evaluated by sampling at 2, 4, 7 and 24 h after injection of GnRH-A, was not different from baseline, whereas after 4, 6 and 8 weeks the levels were significantly lower (*P less than 0.01). The profile of serum T levels was unmodified at the second week, but significantly decreased thereafter (*P less than 0.01). At the end of treatment, the E1 concentrations, elevated in pre-injection condition, were markedly decreased. These data demonstrate that in PCO subjects, GnRH-A significantly lowered the elevated levels of androgens commonly found in these patients. The close correlation observed between reduced serum LH and androgen concentrations suggests that pituitary desensitization could be responsible for the reduction in androgen levels, and may be evidence for a gonadotrophin dependence of the elevated concentrations of T in these patients.

Topics: Adult; Androstenedione; Dihydrotestosterone; Dose-Response Relationship, Drug; Estradiol; Estrone; Female; Follicle Stimulating Hormone; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Ovary; Pituitary Gland; Polycystic Ovary Syndrome; Testosterone; Time Factors

Six nonobese women with polycystic ovarian disease (PCOD) showed significant hyperinsulinemia, compared with controls after oral glucose (P less than 0.05). As an indicator of insulin sensitivity, in vitro proliferation of erythrocyte progenitor cells of PCOD subjects exposed to physiologic concentrations of insulin was significantly blunted (P less than 0.001). Monocyte insulin receptor binding was not impaired in the PCOD subjects. Three of the PCOD patients were treated with a long-acting gonadotropin-releasing hormone agonist for 6 months, which resulted in marked suppression of ovarian androgen secretion but no demonstrable changes in in vivo or in vitro indicators of insulin resistance. Thus insulin resistance in PCOD subjects appears to be unrelated to ovarian hyperandrogenism (or acanthosis or obesity). Although certain tissues are insulin-resistant in PCOD patients, the ovary may remain sensitive and overproduce androgens in response to high circulating insulin levels.

Topics: Adult; Body Weight; Female; Glucose Tolerance Test; Gonadotropin-Releasing Hormone; Hematopoietic Stem Cells; Hormones; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Monocytes; Polycystic Ovary Syndrome; Receptor, Insulin

A long-acting agonist of gonadotropin-releasing hormone (GnRH-a, 100 micrograms/day) was administered daily for 14 days in four patients with polycystic ovarian disease (PCOD) and eight ovulatory women (OW) to determine acute hormone responses. Initiation of GnRH-a treatment in OW on day 5 of their menstrual cycles (OW-day 5) stimulated a greater acute rise of serum follicle-stimulating hormone (FSH) than that seen in OW beginning treatment on day 2 (OW-day 2) or PCOD patients. FSH levels fell to baseline values with repeated injections, whereas luteinizing hormone levels remained elevated in all patients. An acute rise and progressive fall of estradiol (E2) was found in all groups. The OW-day 5 group demonstrated a secondary increase, which by day 14 was clearly greater than that found in the other groups. This secondary increase of E2 in the OW-day 5 group was associated with lower abdominal pain, whereas OW-day 2 and PCOD patients were asymptomatic. For comparison, human menopausal gonadotropin (150 IU/day for 3 days) stimulated a significantly greater increase of E2 in OW-day 5 than in PCOD patients. These studies indicate that daily GnRH-a administration induced variable effects on ovarian function, which depended on when it was begun during the menstrual cycle and whether it was given to ovulatory or PCOD subjects. In addition, abdominal discomfort associated with GnRH-a use in regularly OW can be avoided by commencing agonist administration earlier in their menstrual cycles.

Topics: Abdomen; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormones; Humans; Luteinizing Hormone; Menotropins; Menstrual Cycle; Ovary; Ovulation; Pain; Polycystic Ovary Syndrome; Time Factors