A comprehensive dose-response study of clomiphene citrate for enhancement of the primate ovarian/menstrual cycle.

Despite the increasing use of clomiphene citrate (CC) in normally cycling women undergoing in vitro fertilization, comprehensive data on the dose-response effects of the drug are unavailable. Twenty-four adult, normally cycling monkeys were given CC on cycle days 5 through 9 in doses ranging from 1 mg/kg to 10 mg/kg. Serum estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and progesterone were measured daily. CC stimulated an early, attenuated rise in serum LH which correlated with subsequent follicle development. Concurrently, serum E2 rose to preovulatory levels. No significant increase in serum FSH concentration was seen as a result of CC therapy. No correlation was seen between CC dose and peak levels of E2, LH, or FSH. The ovulatory status of the treatment cycles was also independent of dose. The factors that modulate these hormonal changes may involve direct effects of CC, estrogen feedback, and/or ovarian factors as yet uncharacterized. The individual variation of ovarian response, however, appears to be independent of the dose of CC.