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Clomifene (INN) or clomiphene (USAN and former BAN) or Clomid or Clomifert is a selective estrogen receptor modulator (SERM), increasing production of gonadotropins by inhibiting negative feedback on the hypothalamus. It is used mainly for ovarian stimulation in female infertility due to anovulation (e.g. due to polycystic ovary syndrome). Clomiphene citrate is marketed under various trade names including Clomid, Serophene, Milophene, etc.
[edit] Mode of actionOn day 21 of the menstrual cycle, high levels of estrogen and progesterone cause negative feedback inhibition at the hypothalamus and anterior pituitary. As a result, decreased LH levels leads to atrophy of the corpus luteum, subsequently leading to decreased production of estrogen and progesterone. This will release the feedback inhibition of the hypothalamus and anterior pituitary, causing the FSH level to rise again at day 22. Clomiphene is given at day 2 menses. By that time, FSH level is rising steadily, causing development of a few follicles. Follicles in turn produce the estrogen, which circulates in serum. Clomiphene acts by inhibiting the action of estrogen on the hypothalamus. Zuclomifene, the more active isomer (see below), binds to estrogen receptors and stays bound for long periods of time. This prevents normal receptor recycling and causes an effective reduction in hypothalamic estrogen receptor number. As a result, the body perceives a low level of estrogen, similar to day 22 in the previous cycle. Since estrogen can no longer effectively exert negative feedback on the hypothalamus, GnRH secretion becomes more pulsatile, which results in increased pituitary gonadotropin (FSH, LH) release. Increased FSH level causes growth of more ovarian follicles, and subsequently rupture of follicles resulting in ovulation. [edit] ChemistryClomifene is a mixture of two geometric isomers, enclomifene (E-clomifene) and zuclomifene (Z-clomifene).
[edit] Adverse effectsCommon adverse drug reactions associated with the use of clomifene (≥1% of patients) include: hot flashes, abdominal discomfort, visual blurring (dose-dependent), and/or reversible ovarian enlargement and cyst formation. Infrequent adverse effects (0.1–1% of patients) include: abnormal uterine bleeding, nausea, and/or vomiting. Rare adverse effects (<0.1% of patients) include: reversible alopecia and/or ovarian hyperstimulation syndrome.[1] Clomiphene can lead to multiple ovulation, hence increasing the chance of twins (10% of births instead of the normal ~1%). In comparison to treatment with purified FSH, the rate of ovarian hyperstimulation syndrome is low. There may be an increased risk of ovarian cancer and weight gain. [edit] Use in bodybuildingClomifene is commonly used by male anabolic steroid users to bind the estrogen receptors in their bodies, thereby blocking the effects of estrogen, such as gynecomastia. It also restores the body's natural production of testosterone. It is commonly used as a "recovery drug" and taken toward the end of a steroid cycle.[citation needed] Some users report that taking Clomid increases the amount of fluid produced during ejaculation.[2] [edit] References
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