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.