Clomiphene citrate is a drug of considerable pharmacologic potency. With careful selection and proper management of the patient, clomiphene citrate has been demonstrated to be a useful therapy for the anovulatory patient desiring pregnancy.
Clomiphene citrate is capable of interacting with oestrogen-receptor-containing tissues, including the hypothalamus, pituitary, ovary, endometrium, vagina, and cervix. It may compete with oestrogen for oestrogen-receptor-binding sites and may delay replenishment of intracellular oestrogen receptors. Clomiphene citrate initiates a series of endocrine events culminating in a preovulatory gonadotropin surge and subsequent follicular rupture. The first endocrine event in response to a course of clomiphene citrate therapy is an increase in the release of pituitary gonadotropins. This initiates steroidogenesis and folliculogenesis, resulting in growth of the ovarian follicle and an increase in the circulating level of oestradiol. Following ovulation, plasma progesterone and oestradiol rise and fall as they would in a normal ovulatory cycle.
Available data suggest that both the oestrogenic and anti-oestrogenic properties of clomiphene may participate in the initiation of ovulation. The two clomiphene isomers have been found to have mixed oestrogenic and anti-oestrogenic effects, which may vary from one species to another. Some data suggest that zuclomiphene has greater oestrogenic activity than enclomiphene.
Clomiphene citrate has no apparent progestational, androgenic or anti-androgenic effects and does not appear to interfere with pituitary-adrenal or pituitary-thyroid function.
Although there is no evidence of a ‘carryover effect’ of clomiphene citrate, spontaneous ovulatory menses have been noted in some patients after clomiphene citrate therapy.