The effects of clomiphene citrate on ovarian function in rats

In the present study, the effects of clomiphene citrate (CC) on ovulation, ovarian growth and ovarian steroidogenesis were examined. Ovulation in rats in response to PMSG was completely blocked by administration of three daily treatments of 1.0 mg CC/rat, but was restored by administration of hCG as a preovulatory LH surge substitute. When the number of treatment days was reduced to two days, 1.0 mg of CC enhanced ovulation in response to PMSG, whereas treatment for one day with the same dose of CC did not affect ovulation. The effects of CC on ovulation appear to be dose-dependent. The effects of CC on ovarian growth were similar to the effects of CC on ovulation. The ovarian growth induced by PMSG was inhibited by high doses of CC, while a lower dose had no effect. The inhibition of ovarian growth in terms of ovarian weight by a high dose of CC was restored by hCG given as a preovulatory LH surge. Treatment duration with CC appears to have an important influence on ovarian growth. Three daily treatments with high doses of CC significantly inhibited ovarian growth. However, when the number of treatment days was reduced from three to two, the opposite results were obtained in that CC significantly stimulated ovarian growth. The effects of CC on ovarian steroidogenesis in response to PMSG were dose-dependent. A higher dose of CC significantly stimulated estradiol-17β biosynthesis. Clomiphene citrate did not show any inhibitory effects on progesterone production. Progesterone production was stimulated by hCG in CC treated rats. Lower doses of CC stimulated progesterone and androgen production. Further studies on this are necessary. Histological examination of the ovary revealed that CC selectively inhibited the development of nondominant follicles. The dominant follicles were unaffected as for they were able to develop to the mature stage. These results suggest that the effects of CC on ovulation, ovarian growth and ovarian steroidogenesis are dose-dependent and affected by treatment duration. Clomiphene citrate is assumed to exert its action via a gonadotropic mechanism.Medicine, Faculty ofObstetrics and Gynaecology, Department ofGraduat