Induction of midcycle gonadotropin surge by ovarian steroids in women: a critical evaluation.

Despite major efforts, the roles of estradiol (E2) and progesterone (P4) as signals for triggering the midcycle gonadotropin surge in women remain incompletely defined. In the present study, a preovulatory configuration of E2 and P4 levels was achieved during the midfollicular phase of normal women and in hypogondal women (with E2 implants) by stepwise incremental infusions of E2 and P4. During the 96 h of E2 infusion alone, reproducible and concomitant surges of LH and FSH occurred after latency periods of (mean +/- SE) 58 +/- 6.9 and 68.2 +/- 2.6 h in midfollicular and hypogonadal subjects, respectively. The mean duration of the E2-induced surge was shorter for both normal midfollicular (22.7 +/- 3.9 h) and hypogonadal women (21.8 +/- 2.5 h) than is the spontaneous midcycle surge (48 h). When P4 infusion was superimposed 48 h after the initiation of E2 infusion, a LH/FSH surge that approximated the dimension of the spontaneous surge was achieved in both groups of women. For the hypogonadal women, but not midfollicular women, P4 infusion also advanced the surge onset by 14.7 h (P less than 0.001). Our data represent the first unequivocal demonstration that incremental E2 sustained for about 60 h constitutes the ovarian signal for initiating the midcycle gonadotropin surge and that a small increment of P4 secreted by the preovulatory follicle is required to establish the normal dimension of the surge. Thus, P4, although essential for creating a normal gonadotropic surge, operates by synergizing the obligatory action of E2.