Qualitative differences in estrogenic/antiestrogenic effects of clomiphene and zuclomiphene.

Depending upon the rat assay end point, the estrogenic or antiestrogenic activity of clomiphene (CC) or its isomer, zuclomiphene (Zu), varies considerably. For uterine/body weight ratio, Zu = estradiol greater than CC; for the estrogenic effect on uterine epithelium, Zu greater than estradiol = CC; higher CC doses were antiestrogenic. For endometrial stroma, Zu = estradiol much greater than CC. In the effect of estrogen receptor, low-dose CC = estradiol; high-dose CC was antiestrogenic. For Zu, both doses were about equal and highly antiestrogenic. Essentially the same was seen with progesterone receptor. For plasma LH suppression, Zu much greater than CC much greater than estradiol; but for plasma FSH, estradiol much greater than CC = Zu. The intrinsic estrogenicity of these compounds was made more apparent by the castrate status of the rats. This spectrum of activities may make it possible to select estrogenic or antiestrogenic activities for clinical purposes, depending upon the end-organ effect desired.