Effects of clomiphene on luteal function in the nonpregnant cynomolgus macaque

Abstract

Although estradiol-17β (E2) induces premature regression of the corpus luteum (CL), its role in spontaneous luteolysis which occurs at the end of the nonfertile cycle has not been demonstrated. We compared the effects of an estrogen antagonist on E2-induced and spontaneous luteolysis by administering clomiphene (10 mg/day) to cynomolgus macaques during the luteal phase in the presence and absence of exogenous E2 (supplied by subcutaneous Silastic implants). Other animals received either vehicle or E2 implants. Luteal function was assessed by progesterone concentrations and luteal phase length. Clomiphene maintained normal luteal function in the presence of luteolytic levels of E2 in five of six monkeys. However, clomiphene alone did not prolong luteal function beyond that observed in monkeys receiving vehicle. To assess the direct effect of clomiphene on the CL, we incubated monkey luteal cells with human chorionic gonadotropin and clomiphene, E2, or clomiphene plus E2. Clomiphene (1500 ng/ml) alone and E2 (1000 ng/ml) alone significantly (P<0.05) inhibited progestin production. Clomiphene and E2 together depressed progestin production to an even greater extent. The data suggest that the mechanisms involved in E2-induced and spontaneous luteolysis differ.