Evidence for a specific role of GnRH pulse frequency in the control of the human menstrual cycle.

An adequate frequency of gonadotropin-releasing hormone (GnRH) pulses appears to be important for physiological gonadotropin secretion. However, limited information exists on the exact role of this parameter in the regulation of the human menstrual cycle. Thus we studied gonadotropin and gonadal steroid secretion in 32 women with primary hypogonadotropic amenorrhea who received pulsatile GnRH (60 to 120 micrograms/day) at 60- or 120-min intervals for a total of 64 ovulation induction cycles. Ovulation was achieved in 94% of 60-min and in 70% of 120-min cycles P less than 0.05). In the follicular phase of ovulatory cycles, estradiol (E2) levels did not differ among the four groups; however, mean luteinizing hormone (LH) levels were lower (P less than 0.005), and the midcycle LH surge was severely blunted in cycles of subjects receiving 120 micrograms/day (5 micrograms/bolus) GnRH every 120 min compared with subjects receiving the same dose of GnRH per day or per bolus every 60 min. Luteal progesterone (only in 60 micrograms/day GnRH cycles) and E2 levels were lower in 120-min than in 60-min cycles (P less than 0.05). The use of the higher daily GnRH dose (120 micrograms/day) reduced or abolished the frequency-associated hormone level differences. We conclude that a low frequency of pulsatile GnRH in women 1) decreases mean LH levels and blunts the midcycle gonadotropin surge, 2) does not increase follicle-stimulating hormone concentrations, and 3) is associated with a reduced rate of ovulation.