EVEN AFTER PRIMING WITH OVARIAN-STEROIDS OR PULSATILE GONADOTROPIN-RELEASING-HORMONE ADMINISTRATION, NALTREXONE IS UNABLE TO INDUCE OVULATION IN WOMEN WITH FUNCTIONAL HYPOTHALAMIC AMENORRHEA

In functional hypothalamic amenorrhea (HA), it has been reported that administration of opioid receptor antagonists restores gonadotropin se cretion and ovarian function. However, endogenous opioids may modulate gonadotropin secretion only in the presence of ovarian steroids. To f urther study these conflicting results, a group of nine women with sec ondary functional HA who wished to become pregnant were studied. The o piate antagonist naltrexone (Nal; 100 mg/day) was administered for two 30-day periods, starting on either day 22 (Nal 1) of a well character ized replacement regimen with estradiol (E(2)) and progesterone (P) or on day 22 (Nal 2) of the luteal phase induced by erogenous pulsatile GnRH administration (10 mu g/pulse, iv, every 90 min). Plasma LH and F SH were measured every 10 min for 8 h before treatment and on day 12 o f each treatment period (Nai 1, pulsatile GnRH, and Nal 2). Ovulation was monitored during each treatment. Plasma E(2) levels were measured on days 12 and 22, and P levels on day 22 of each treatment. During ex ogenous E(2) and P administration, plasma steroid levels reached lutea l phase levels. However, during Nal 1, plasma E(2) levels fell to pres tudy levels and remained low. No follicular growth occurred, and the p ulsatile study showed pretreatment frequency, amplitude, and mean plas ma levels of LH. On day 12 of pulsatile GnRH administration, plasma E( 2) levels increased, and LH and FSH pulses followed each GnRH pulse du ring the frequent sampling study. Ovulation occurred in all women duri ng pulsatile GnRH treatment. During Nal 2 treatment, plasma E(2) level s returned to prestudy levels without follicular growth, and the pulsa tile study was similar to those prior treatment and during Nai 1 admin istration. In conclusion, Nal, started during priming either with exog enous E(2) and P treatment or gonadotropin stimulation induced by puls atile GnRH administration, was unable when continued alone to initiate or maintain gonadotropin secretion in women with HA. Thus, the exclus ive role of opioids in HA and the effect of Nal even in the presence o f ovarian steroids are questionable.