Effect on plasma gonadotropins of cyclic steroid replacement in women with premature ovarian failure.

A sequential regimen of steroid replacement of oral estradiol valerate and progesterone (P) by intravaginal suppository was developed for women with premature ovarian failure or ovarian agenesis. The regimen, based on a 28-day cycle, resulted in peripheral plasma concentrations of estradiol and P within the normal range of the menstrual cycle and endometrial differentiation consistent with the normal secretory phase. Pregnancy has now been successfully established in four patients following this regimen of steroid treatment and transfer of donated embryos. Plasma concentrations of LH were within the normal range by the end of the first cycle of treatment with exogenous steroids. However, plasma FSH remained above the normal range, even during the third treatment cycle, consistent with the necessity of a gonadal feedback factor (inhibin?) other than estradiol and P for maintaining FSH in the normal range. Although 7/8 patients had a surge of LH at midcycle, only 3/8 patients had concomitant FSH surges, supporting a role for progesterone in facilitating the midcycle FSH surge.