Enclomiphene vs Clomiphene: Drug Comparison

Enclomiphene is a non-steroidal selective estrogen receptor modulator (SERM) sometimes used to treat male secondary hypogonadism, or low testosterone caused by problems with the hypothalamus or pituitary gland. The medication is derived from another SERM called clomiphene citrate, and while enclomiphene is not approved by the United States Food and Drug Administration (FDA) to treat any condition on its own, it is available through compounding pharmacies.

Enclomiphene is designed to stimulate testosterone production while minimizing the estrogenic side effects sometimes seen with clomiphene, such as breast tissue growth. It works by blocking estrogen signals in the brain, which increases the release of certain hormones, like luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These hormones then tell the testicles to produce more natural testosterone.

Enclomiphene is taken as a daily pill, usually in doses of 12.5 milligrams (mg) to 25 mg.

Enclomiphene boosts testosterone while helping the body maintain its natural hormone production and sperm count, making it a good alternative to traditional testosterone replacement therapies for men who want to preserve their fertility.

Commonly sold as brand-name Clomid^®, clomiphene citrate was initially developed as a fertility medication for women. It is now commonly prescribed as an off-label treatment for male hypogonadism. As a selective estrogen receptor modulator, clomiphene exerts both estrogenic and antiestrogenic properties due to its mix of enclomiphene and zuclomiphene. Enclomiphene blocks the negative feedback of estrogen on the brain, which leads to an increase in gonadotropin-releasing hormone (GnRH) and an increase in luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Elevated levels of LH and FSH then stimulate the testes to produce more testosterone and sperm.

Selective estrogen receptor modulator

Selective estrogen receptor modulator

Enclomiphene is not approved as a drug in the United States

Clomid (clomiphene citrate) is indicated:

• For the treatment of ovulatory dysfunction in women desiring pregnancy

• Typically taken orally

• Often prescribed at 6.25 mg, 12.5 mg, and 25 mg doses

• Typically taken orally once daily for five days

• Comes as 50 mg tablets

Information about enclomiphene is limited

Incidence of adverse events in clinical studies (events >1%):

• Ovarian enlargement

• Vasomotor flushes

• Abdominal-pelvic discomfort/distension/bloating

• Nausea and vomiting

• Breast discomfort

• Visual symptoms

• Headache

• Abnormal uterine bleeding

Information about enclomiphene is limited

• Clomiphene citrate is contraindicated in patients with a known hypersensitivity or allergy to clomiphene citrate or to any of its ingredients

• Clomiphene citrate use in pregnant women is contraindicated, as clomiphene citrate does not offer benefit in this population

• Clomiphene citrate therapy is contraindicated in patients with liver disease or a history of liver dysfunction

• Clomiphene citrate is contraindicated in patients with abnormal uterine bleeding of undetermined origin

• Clomiphene citrate is contraindicated in patients with ovarian cysts or enlargement not due to polycystic ovarian syndrome

• Clomiphene citrate is contraindicated in patients with uncontrolled thyroid or adrenal dysfunction or in the presence of an organic intracranial lesion such as pituitary tumor

• Drug interactions: Drug interactions with clomiphene citrate have not been documented

Information about enclomiphene is limited

• Patients should be advised that blurring or other visual symptoms such as spots or flashes (scintillating scotomata) may occasionally occur during therapy with clomiphene citrat

• The ovarian hyperstimulation syndrome (OHSS) has been reported to occur in patients receiving clomiphene citrate therapy for ovulation induction

• Careful attention should be given to the selection of candidates for clomiphene citrate therapy. Pelvic examination is necessary prior to clomiphene citrate treatment and before each subsequent course

• Pregnancy: Clomiphene citrate use in pregnant women is contraindicated, as clomiphene citrate treatment does not offer benefit in this population

• Breastfeeding: It is not known whether clomiphene citrate is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised if clomiphene citrate is administered to a nursing woman. In some patients, clomiphene citrate may reduce lactation

Information about enclomiphene is limited. It is the active isomer of clomiphene.

*This information is from the label for brand name Clomid^®. See the Full Prescribing Information for more complete information. Clomiphene citrate, the active ingredient in Clomid, may also be the active ingredient in other medications, and this information may not be accurate for all medications that include the active ingredient clomiphene citrate.