Acute Gonadotropin Release Induced by Exogenous Estradiol During the Mid-Follicular Phase of the Menstrual Cycle

During the mid-follicular phase of the cycle (D7-9), a rapid increase in serum estradiol levels was induced via 17β-estradiol infusion, ethinyl estradiol and estradiol benzoate administration in a fashion simulating the pre-ovulatory rise and this elicited an acute release of LH to a lesser degree FSH, in 5 of 7 subjects studied. During treatment (1–3 days) a uniform suppression of gonadotropin levels was noted. This negative feedback effect was followed by the onset of an acute surge of both gonadotropins which occurred 12–24 hrs after the termination of treatment when a consistent drop of serum estradiol concentrations was observed. In three subjects the induced LH-FSH surge was comparable to those occurring spontaneously at midcycle, but without evidence of ovarian response either in ovulation or in the enhanced estradiol secretion. In all subjects, this transient disruption of the normal sequence of gonadotropin secretion was associated with an impairment of follicular maturation as reflected by the low estradiol levels and the prolongation of the follicular phase. The subsequent time course mimicked a newly initiated cycle with an inversed relationship between serum estradiol and gonadotropin concentrations. These data suggest that the negative and positive feedback action of ovarian estradiol modulates the tonic secretion of gonadotropins during the human menstrual cycle and supports the hypothesis that the rapid rise (or acute fall) in serum estradiol levels during the late follicular phase provides a major ovarian signal for triggering the gonadotropin surge at midcycle.