Effect of clomiphene citrate on the rabbit ovary

The effect of clomiphene citrate on the rabbit ovary was studied in mature nulliparous rabbits pretreated with three consecutive doses ranging from 0.01-10.0 mg/kg per day. With increasing doses a trend of decrease in mean ovarian weight (mg/kg body weight) is observed 2 days after termination of treatment. Five days later a significant increase occurs, which then subsides again to control values on day 12 after termination of treatment. During this period, no matings or injections of luteinizing hormone were performed to trigger ovulation; consequently no ovulations are observed. Folliculogenesis appears as normally; number and morphology of follicles are within normal ranges. No endogenous, spontaneous gonadotropin surges are detected in blood serum up to the 7th day after termination of treatment (2 and 10 mg doses). The surface epithelium of the ovary resembles normal germinal epithelium; however, after treatment with high doses a "secretory"-like activity is observed, accompanied with ultrastructural changes.