EFFECTS OF CHRONIC OPIOID ANTAGONISM ON GONADOTROPIN AND OVARIAN SEX STEROID-SECRETION DURING THE LUTEAL-PHASE

OBJECTIVES Since short-term opioid antagonism increases LH pulsatility during the luteal phase in women, we postulated that prolonged opioid antagonism may also accelerate the LH secretory episodes at this time . If so, the functional and temporal links between secretory episodes of pituitary LH and oestradiol (E-2) and progesterone (P) release from the mature human corpus luteum may be disrupted. STUDY DESIGN Prolong ed opioid blockade with the oral antagonist naltrexone (100 mg daily) was effected in eight women during the entire luteal phase of their cy cles. Following documented ovulation in both placebo (control) and nal trexone cycles, blood samples were obtained daily and frequently (ever y 10 minutes for 10 h) on days 6-8 after ovulation, MEASUREMENTS In al l blood samples, LH, E-2 and P were determined by IRMA, RESULTS Compar ed to control cycles, the temporal organization and the endocrine char acteristics of the luteal phase remained virtually unchanged during ch ronic opioid blockade, Periodic fluctuations were detected (by cluster analysis) in LH, E-2 and P data series established by frequent sample collections in both the control and naltrexone cycles. LH secretory p rofiles were remarkably similar during control and naltrexone cycles, and the E-2 and P secretory episodes tended to be coupled to LH pulses during both cycles, As determined by time-series analysis, the cross- correlations between the LH/E-2 and LH/P data series remained unaltere d by opioid blockade. CONCLUSIONS Chronic opioid antagonism with naltr exone did not disrupt the temporal organization or endocrine character istics of the luteal phase, In particular, prolonged opioid blockade d id not change LH secretory patterns. The functional and temporal links between LH inputs and sex steroid release from the mature corpus lute um remained unaffected by prolonged opioid antagonism. In contrast to the effects of short-term opioid blockade on LH pulsatile release duri ng the luteal phase, the effects of chronic opioid antagonism on LH re lease may be transient and may not persist throughout the entire lutea l phase, suggesting desensitization of the opiate receptors.