IS OPIOIDERGIC ACTIVITY RESPONSIBLE FOR THE CIRCADIAN VARIATION OBSERVED IN THE GONADOTROPIN RESPONSIVENESS OF EARLY FOLLICULAR PHASE WOMEN

OBJECTIVES In women, the gonadotrophin response to gonadotrophin-relea sing hormone (GnRH) displays a circadian rhythm during the early folli cular phase (EFP), with GnRH-stimulated luteinizing hormone (LH) and f ollicle-stimulating hormone (FSH) release found to be markedly decreas ed at night, Since the opioidergic inhibition of gonadotrophin secreti on is selectively enhanced at night, we reasoned that the circadian ch anges in the gonadotrophin responsiveness to GnRH might be related to a nocturnal increase of opioidergic activity. STUDY DESIGN Eleven wome n with normal menstrual cycles were studied in the EFP on four differe nt occasions in random order. Studies were conducted either during the day (0900-1300 h) or at night (2100-0100h). During these times, GnRH (25 mu g i.v,) was administered in conjunction with either saline las control) or naloxone (4 mg i.v.). MEASUREMENTS Frequent blood samples were obtained before and after GnRH stimulation for determination of b asal sex steroid and gonadotrophin concentrations by immunoradiometric assays. RESULTS While oestradiol levels were comparable (P>0.3) at al l times, progesterone concentrations were significantly (P<0.01) highe r during day than during night hours, with no difference between contr ol and naloxone conditions, Gonadotropin responses to GnRH stimulation were not significantly different between day and night times, nor did they vary between control and naloxone conditions. CONCLUSIONS Opioid ergic blockade imposed by naloxone did not noticeably change GnRH-stim ulated gonadotrophin release at any of the study times, We therefore i nfer that mechanisms other than a nocturnal increase of opioidergic in hibition may account for eventual circadian changes in the gonadotroph in responsiveness of early follicular phase women.