Sleep-associated decrease in luteinizing hormone pulse frequency during the early follicular phase of the menstrual cycle: evidence for an opioidergic mechanism.

To investigate the possible role of an opioidergic mechanism(s) in the sleep-associated decrease in LH pulse frequency during the early follicular phase of the menstrual cycle, 10 normal cycling women were studied on days 3 and 4 of their cycles before and after the administration of a specific opiate receptor antagonist, naloxone. Sequential 24-h infusions of naloxone (10-mg iv bolus dose followed by an infusion of 30 micrograms/kg . h) or NaCl were administered randomly. Pulsatile LH activity was assessed for 48 h. Sleep was confirmed by electroencephalogram monitoring during the night hours (2300-0700 h). Significant sleep-associated decreases in LH pulse frequency (P less than 0.01) and mean serum LH levels (P less than 0.01) were found during the NaCl control studies. While naloxone infusion had no effect on LH pulse frequency during the waking hours, it prevented the sleep-associated decrease in pulse frequency and, in fact, significantly (P less than 0.001) increased the LH pulse frequency during the sleeping hours. These observations provide evidence that a diurnal variation of naloxone sensitivity exists in early follicular phase women and that the decrease in LH pulse frequency normally found during sleep is based at least in part on increased opioidergic inhibition.