Role of endogenous opioids in reducing the frequency of pulsatile luteinizing hormone secretion induced by progesterone in normal women.

It is well-established that the frequency of LH pulses varies during the normal menstrual cycle with a significant reduction in frequency in the luteal phase. Previous studies have indicated that both progesterone and opioids are able to reduce the frequency of LH pulses and in this study we sought to clarify the possible interaction between progesterone, endogenous opioids and GnRH neurons. Sixteen normal women in the mid-follicular phase (days 8-12) were randomly allocated to a control or treatment group and LH pulsatility assessed on one or two occasions by taking blood samples at 15 min intervals over 8 h. For the control women, LH pulsatility was assessed on one occasion during a saline infusion. The treated women received progesterone (50-100 mg/d for 7 d) at the end of which LH pulsatility was assessed before and after a naloxone infusion (2 mg/h for 8 h). Mean +/- SEM LH pulse frequency in the control women was 4.9 +/- 0.5 pulses/8 h which was significantly decreased to 3.0 +/- 0.3 pulses/8 h (P less than 0.01) in the progesterone treated women but not different from 5.5 +/- 0.3 pulses/8 h in those also treated with naloxone. Mean +/- SEM LH pulse amplitude in the control women was 2.3 +/- 0.3 IU/l, which was significantly increased to 4.8 +/- 0.7 IU/l (P less than 0.05) in the progesterone treated group, and to 3.7 +/- 0.4 IU/l (P less than 0.05) in the progesterone-treated women after naloxone. We conclude that progesterone slows the frequency of LH pulsatility by increasing endogenous opioid activity in the hypothalamus which may in turn inhibit the firing rate of the GnRH neurons.

RCT Entities:   Population Interventions Outcomes