IS GNRH REDUCED AT THE MIDCYCLE SURGE IN THE HUMAN - EVIDENCE FROM A GNRH-DEFICIENT MODEL

Recent studies indicate that the midcycle gonadotropin surge in the hu man occurs without an increase in hypothalamic gonadotropin-releasing hormone (GnRH) pulse frequency. In addition, previous studies employin g a GnRH antagonist to provide a semiquantitative estimate of endogeno us GnRH secretion suggest that the overall amount of GnRH secreted is decreased at the time of the surge. To investigate the hypothesis that a normal gonadotropin surge can be generated in the human with a decr eased amount of GnRH at the midcycle, 7 GnRH-deficient subjects underw ent two cycles of a physiologic regimen of intravenous pulsatile GnRH therapy. In the control cycle, 75 ng/kg/bolus of GnRH, a dose known to be sufficient for folliculogenesis, was administered throughout the c ycle, using physiological frequencies. In a second cycle, the bolus do se of GnRH was decreased by one-half log order to 25 ng/kg just prior to the luteinizing hormone surge and returned to 75 ng/kg after docume nted ovulation, All cycles were ovulatory. The peak luteinizing hormon e level (77.4 +/- 9.7 vs. 67.5 +/- 17.6 IU/l) did not differ between t he control and decreased GnRH cycles. There was no difference in the p eak serum estradiol level (475.8 +/- 144.1 vs. 493.2 +/- 93.0 pg/ml), follicular phase length (15.0 +/- 1.3 vs. 14.8 +/- 0.6 days), or proge sterone level (22.4 +/- 5.1 vs. 34.8 +/- 5.7 ng/ml) on day 6 of the lu teal phase in the control and decreased GnRH cycles, respectively. Thr ee pregnancies were achieved in each of the control and reduced GnRH c ycles. We conclude that a decreased overall amount of GnRH generates a normal midcycle gonadotropin surge and has no significant impact on l uteal phase adequacy or fertility. These results provide further evide nce that a decrease in endogenous hypothalamic GnRH secretion may occu r at the midcycle in normal women. This study also provides evidence t hat the GnRH requirements for normal follicular and luteal phase dynam ics may well be greater than those required for generation of a normal midcycle gonadotropin surge and ovulation in women.