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.