Induction of multiple follicular growth by pulsatile gonadotrophin-releasing hormone (GnRH) treatment in women with normal cycles: the role of the route of administration.

In a prospective study, seven patients with normal menstrual cycles were treated with pulsatile gonadotrophin-releasing hormone. They received one cycle of intravenous (i.v.) therapy and one cycle of subcutaneous (s.c.) therapy. Another four volunteers with normal cycles were treated for one s.c. cycle only. Cycles were compared to each other and to the normal unstimulated cycles of 14 other volunteers. Multiple follicular development could be achieved using both the i.v. and the s.c. routes. However, the i.v. route showed significantly higher luteinizing hormone (LH) and luteal steroid levels. Comparing s.c. cycles to controls, significantly lower LH levels were observed, resulting in significantly lower steroid production if calculated per large follicle. We conclude that the i.v. route is superior to the s.c. route in inducing multiple follicular growth in women with normal cycles.

Pulsatile luteinizing hormone secretion in hypothalamic amenorrhea, anorexia nervosa, and polycystic ovarian disease during naltrexone treatment.

OBJECTIVE: To determine if chronic treatment with the long-acting oral opioid antagonist naltrexone can increase luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion in women with secondary amenorrhea. DESIGN: Prospective. SETTING: Large reproductive endocrinology unit of an academic hospital. PATIENTS: Three groups of women with oligomenorrhea or amenorrhea: (1) hypothalamic amenorrhea; (2) anorexia nervosa; and (3) polycystic ovarian disease (PCOD). INTERVENTION: Naltrexone 50 mg every day for 4 days. MAIN OUTCOME MEASURES: Luteinizing hormone pulse pattern, frequency and amplitude, mean LH and FSH levels, measured by serial blood sampling over a 6-hour period before and after naltrexone. RESULTS: Naltrexone caused a significant increase (P less than 0.05) of the LH pulse frequency in patients with hypothalamic amenorrhea and in PCOD but not in anorexia nervosa. The mean levels of LH and FSH and LH pulse amplitudes were not significantly changed by naltrexone. The naltrexone nonresponders were underweight either because of simple weight loss or anorexia nervosa and had low levels of estradiol and an LH pulse pattern similar to the luteal one. CONCLUSION: The luteal LH pulse pattern in weight loss-related amenorrhea is caused by a nonopioid, undernutrition-linked factor.

Effects of opioid antagonism with naltrexone on pulsatile luteinizing hormone secretion in women with hypothalamic amenorrhea in basal conditions and after discontinuation of treatment with pulsatile LHRH.

Although endogenous opioids seem to play an important role in the inhibition of luteinizing hormone releasing hormone (LHRH) secretion in women with hypothalamic amenorrhea, opioid antagonism does not always cause an increase of pituitary luteinizing hormone (LH) secretion. The effect of the long-acting oral opiate antagonist naltrexone on pulsatile LH secretion was studied in eight women with weight loss and exercise-related hypothalamic amenorrhea. LH pulse studies and LHRH tests were performed in basal conditions and after 4 days of naltrexone treatment, 50 mg q.d. Naltrexone caused a slight, but significant increase of LH pulse frequency. Six weeks later, a second experiment was performed. The response to naltrexone was studied after enhancement of the pituitary sensitivity. Patients were pretreated with pulsatile LHRH during 4 days, followed by naltrexone 50 mg q.d. during 4 days. An increased LH response to LHRH, but no response to naltrexone, were seen after discontinuation of pulsatile LHRH. It is concluded that the limited pituitary response to opioid antagonism, observed in weight loss-related forms of hypothalamic amenorrhea, is not caused by pituitary insensitivity to LHRH.