Clomifene

From Wikipedia, the free encyclopedia

Clomifene (INN) or clomiphene (USAN and former BAN) or Clomid or Clomifert is a selective estrogen receptor modulator (SERM) that increases 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, and Milophene.
Contents[hide]
1 Mode of action
2 Chemistry
3 Adverse effects
4 Off-label use in the treatment of male hypogonadism (Low T)
5 Prohibited use in sports and use in bodybuilding
6 References
7 External links
//
[edit] Mode of action
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 fertilisation 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 oestrogen levels during pregnancy.
Therapeutically, clomiphene is given at day 2 of 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 pituitary. 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] Chemistry
Clomifene is a mixture of two geometric isomers, enclomifene (E-clomifene) and zuclomifene (Z-clomifene).

Enclomifene

Zuclomifene
[edit] Adverse effects
Common adverse drug reactions associated with the use of clomifene (≥1% of patients) include: vasomotor flushes (or 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% title="Alopecia" href="http://en.wikipedia.org/wiki/Alopecia">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. Some patients may experience vivid and/or disturbing dreams. When used as a fertility drug in men it can have the opposite effect and actually reduce the users sperm counts. Although this risk occurs in less than 5% of male users.
[edit] Off-label use in the treatment of male hypogonadism (Low T)
Clomiphine citrate has been found very effective in the treatment of secondary male hypogonadism in many cases.[2] 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.[3] Unlike traditional TRT it also does not shrink the testes and as a result can enhance fertility. Traditional TRT can render a man sterile.[4] Because clomiphene 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 there would be no profit incentive.[5] However, the single isomer of clomiphine "enclomiphene" under the brand name Androxal is currently under phase 2 trials for use in men.[6][7]
[edit] Prohibited use in sports and use in bodybuilding
Clomifene 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] It is included on the World Anti-Doping Agency list of illegal doping agents in sport.[8] Some users report that taking Clomid increases the amount of fluid produced during ejaculation, which make it a fertility drug option for men as well.