Is opioidergic activity responsible for the circadian variation observed in the gonadotrophin responsiveness of early follicular phase women?

OBJECTIVES

In women, the gonadotrophin response to gonadotrophin-releasing hormone (GnRH) displays a circadian rhythm during the early follicular phase (EFP), with GnRH-stimulated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release found to be markedly decreased at night. Since the opioidergic inhibition of gonadotrophin secretion is selectively enhanced at night, we reasoned that the circadian changes in the gonadotrophin responsiveness to GnRH might be related to a nocturnal increase of opioidergic activity.

STUDY

DESIGN

Eleven women with normal menstrual cycles were studied in the EFP on four different occasions in random order. Studies were conducted either during the day (0900-1300 h) or at night (2100-0100 h). During these times, GnRH (25 micrograms i.v.) was administered in conjunction with either saline (as control) or naloxone (4 mg i.v.).

MEASUREMENTS: Frequent blood samples were obtained before and after GnRH stimulation for determination of basal sex steroid and gonadotrophin concentrations by immunoradiometric assays.

RESULTS

While oestradiol levels were comparable (P > 0.3) at all times, progesterone concentrations were significantly (P < 0.01) higher during day than during night hours, with no difference between control 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

Opioidergic blockade imposed by naloxone did not noticeably change GnRH-stimulated gonadotrophin release at any of the study times. We therefore infer that mechanisms other than a nocturnal increase of opioidergic inhibition may account for eventual circadian changes in the gonadotrophin responsiveness of early follicular phase women.