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Effect of Clomiphene Citrate and Its Isomers on Sexual Behavior in Ovariectomized Rats¹

Department of Anatomy and Brain Research Institute, UCLA School of Medicine Los Angeles, California 90024
Department of Obstetrics and Gynecology, Harbor General Hospital Torrance, California

Abstract

The effects of clomiphene citrate and its two isomers were evaluated as to their ability to induce sexual receptivity in ovariectomized rats. Ten–µg, 100–µg, 1–mg and 10–mg doses of either cis—clomiphene—, trans—clomiphene—, or racemic clomiphene—citrate were given to individual groups of 8 rats for 10 days. On the eleventh day each group received 500 µg sc of progesterone in oil. Ten mount behavior tests were performed on the afternoon of treatment days 5, 10 and 11. One mg of trans—clomiphene citrate caused a significant increase in the lordosis response on day 5. Cis—clomiphene citrate was ineffective in facilitating the lordosis response. Racemic clomiphene citrate, alone, caused a significant increase in the lordosis response after 10 mg per day for 10 days and treatment with progesterone increased the lordosis response in animals treated with either 1 or 10 mg per day. Based on the response to trans—clomiphene, clomiphene citrate did not cause as significant an increase in the lordosis response as would be expected for a racemic mixture. Similarly, the trans isomer was 10 times more effective than the cis isomer in causing vaginal cornification and 20 times more effective than clomiphene citrate. Because of these unexpected responses with the racemic form of clomiphene it is suggested that the cis isomer may interfere with the trans isomer. It is concluded that the trans isomer of clomiphene is particularly effective in facilitating sexual behavior. (Endocrinology 92: 1079, 1973)

Footnotes

¹ Supported by USPHS Grant HD-01182 and the Ford Foundation.

Received July 17, 1972.