Also Known As: Clomifene, Clomid, Clomiphene, Serophene

Clomifene (INN) or clomiphene (USAN) (also known as Clomifert), marketed as Clomid, is a selective estrogen receptor modulator (SERM) that increases production of gonadotropins by inhibiting negative feedback on the hypothalamus. It is used mainly in female infertility, in turn mainly as ovarian stimulation[disambiguation needed ] to reverse oligoovulation or anovulation such as in infertility in polycystic ovary syndrome, as well as being used for ovarian hyperstimulation, such as part of an in vitro fertilization procedure. Clomifene citrate is marketed under various trade names including Clomid, Serophene, and Milophene.

Clomifene appears to inhibit estrogen receptors in hypothalamus, thereby inhibiting negative feedback of estrogen on gonadotropin production.[1] It may also result in direct stimulation of the hypothalamic–pituitary–adrenal axis.[1] Zuclomifene, a more active isomer, stays bound for long periods of time.

In normal physiologic female hormonal cycling, at 7 days past ovulation, high levels of estrogen and progesterone produced from the corpus luteum inhibit GnRH, FSH and LH at the hypothalamus and anterior pituitary. If fertilization does not occur in the post-ovulation period the corpus luteum disintegrates due to a lack of beta-hCG. This would normally be produced by the embryo in the effort of maintaining progesterone and estrogen levels during pregnancy.

Therapeutically, clomifene is given early in the menstrual cycle. It is typically prescribed beginning on day 1, 3 or 5 and continuing for 5 days. By that time, FSH level is rising steadily, causing development of a few follicles. Follicles in turn produce the estrogen, which circulates in serum. In the presence of clomifene, 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 rapidly pulsatile, which results in increased pituitary gonadotropin (FSH, LH) release. (It should be noted that more rapid, lower amplitude pulses of GnRH lead to increased LH/FSH secretion, while more irregular, larger amplitude pulses of GnRH leads to a decrease in the ratio of LH/FSH.) Increased FSH level causes growth of more ovarian follicles, and subsequently rupture of follicles resulting in ovulation

Clomifene citrate has been found very effective in the treatment of secondary male hypogonadism in many cases.[3] This has shown to be a much more attractive option than testosterone replacement therapy (TRT) in many cases because of the reduced cost and convenience of taking a pill as opposed to testosterone injections or gels.[4] Unlike traditional TRT it also does not shrink the testes and as a result can enhance fertility. Traditional TRT can render a man sterile (although with careful monitoring and low-dose hCG as an adjunct, this is both preventable and reversible for most men).[5] Because clomifene citrate has not been FDA approved for use in males it is prescribed off-label. According to Professor Craig Niederberger, because this drug is now generic, no drug company would pursue FDA approval for use in men now because of limited profit incentive, mostly due to the relatively small market potential.[6] However, the single isomer of clomifene "enclomiphene" under the brand name Androxal is currently under phase 2 trials for use in men

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