New Evidence for an Anti-estrogenic Action of Clomiphene Citrate in Women

Abstract

Nineteen regularly menstruating women were given either 0.1 mg of ethinyl estradiol alone or in combination with 200 mg of clomiphene citrate for 8 consecutive days starting with the onset of menses. Ethinyl estradiol decreased plasma FSH concentrations and abolished the normal progressive follicular rise of LH. Five to 9 days after discontinuing ethinyl estradiol, 7 of 10 subjects had withdrawal bleeding. When clomiphene was given with ethinyl estradiol, gonadotropin levels were normal throughout the cycle and there was no withdrawal bleeding. Plasma 17-hydroxyprogesterone levels in the latter treatment group were higher than those in the ethinyl estradiol group, although in neither group were 17-hydroxyprogesterone or progesterone levels consistent with normal corpus luteum function. Short luteal phases were encountered in both groups. When subjects, irrespective of treatment, were categorized according to duration of luteal phase, then those women with luteal phases of 10 days or less had lower FSH, progesterone and 17-hydroxyprogesterone levels than those with longer luteal phases. We conclude that 1) clomiphene probably competes with estrogen at receptor sites in the pituitary gland or hypothalamus, 2) alteration of gonadotropin secretion in the first part of the follicular phase alters subsequent physiologic events in that treatment cycle, and 3) low follicular phase levels of FSH are associated with subsequent short luteal phases.