Tamoxifen Vs Enclomiphene: 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.

Tamoxifen citrate is an oral selective estrogen receptor modulator (SERM) approved since the 1970s for breast cancer. Tamoxifen is sometimes prescribed off-label for men with low testosterone. As an estrogen antagonist, tamoxifen blocks estrogen’s negative feedback on the hypothalamic-pituitary-gonadal (HPG) axis, increasing the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Increases in LH and FSH stimulate testosterone production and sperm production. While most studies of tamoxifen in men focus on infertility, the drug’s mechanism of action suggests potential use for raising testosterone in men with low levels, especially if estradiol levels are too high.

Selective estrogen receptor modulator

Nonsteroidal antiestrogen

Enclomiphene is not approved as a drug in the United States

Tamoxifen is indicated for:

• Metastatic breast cancer

• Adjuvant treatment of breast cancer

• Ductal carcinoma in situ

• Reduction in breast cancer incidence in high risk women

• Typically taken orally

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

• Typically taken orally once or twice daily

• Comes in 10 mg and 20 mg tablets

Information about enclomiphene is limited

Common side effects include:

• Hot flashes

• Vaginal discharge

Information about enclomiphene is limited

• Patients with known hypersensitivity to the drug or any of its ingredients

• Women who require concomitant coumarin-type anticoagulant therapy or in women with a history of deep-vein thrombosis or pulmonary embolus

• Drug interactions: Coumarin-type anticoagulants, cytotoxic agents, letrozole, anastrozole, and others—see Full Prescribing Information

Information about enclomiphene is limited

• As with other additive hormonal therapy (estrogens and androgens), high blood calcium has been reported in some breast cancer patients with bone metastases within a few weeks of starting treatment with tamoxifen

• An increased incidence of uterine malignancies has been reported in association with tamoxifen treatment

• An increased incidence of endometrial changes including hyperplasia and polyps has been reported in association with tamoxifen treatment

• There is evidence of an increased incidence of thromboembolic events, including deep-vein thrombosis and pulmonary embolism, during tamoxifen therapy

• Effects on the liver

• A number of second primary tumors, occurring at sites other than the endometrium, have been reported following the treatment of breast cancer with tamoxifen in clinical trials

• Ocular disturbances, including corneal changes, decrement in color vision perception, retinal vein thrombosis, and retinopathy have been reported in patients receiving tamoxifen. An increased incidence of cataracts and the need for cataract surgery have been reported in patients receiving tamoxifen

• Decreases in platelet counts, usually to 50,000 to 100,000/mm³, infrequently lower, have been occasionally reported in patients taking tamoxifen for breast cancer

• Pregnancy: Teratogenic effects

• Breastfeeding: Tamoxifen has been reported to inhibit lactation. It is not known if tamoxifen citrate is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from tamoxifen, women taking tamoxifen should not breast feed

WARNING: For Women With Ductal Carcinoma in Situ (DCIS) and Women at High Risk for Breast Cancer

Serious and life-threatening events associated with tamoxifen in the risk reduction setting (women at high risk for cancer and women with DCIS) include uterine malignancies, stroke and pulmonary embolism. Incidence rates for these events were estimated from the NSABP P-1 trial. Uterine malignancies consist of both endometrial adenocarcinoma (incidence rate per 1,000 women-years of 2.20 for tamoxifen vs. 0.71 for placebo) and uterine sarcoma (incidence rate per 1,000 women-years of 0.17 for tamoxifen vs. 0.4 for placebo)*. For stroke, the incidence rate per 1,000 women-years was 1.43 for tamoxifen vs. 1.00 for placebo**. For pulmonary embolism, the incidence rate per 1,000 women-years was 0.75 for tamoxifen versus 0.25 for placebo**.

Some of the strokes, pulmonary emboli, and uterine malignancies were fatal.

Health care providers should discuss the potential benefits versus the potential risks of these serious events with women at high risk of breast cancer and women with DCIS considering tamoxifen to reduce their risk of developing breast cancer.

The benefits of tamoxifen citrate outweigh its risks in women already diagnosed with breast cancer.

*Updated long-term follow-up data (median length of follow-up is 6.9 years) from NSABP P-1 study.

**See Table 3 in the Full Prescribing Information

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

*This information is from the tamoxifen citrate label used by Actavis Pharma, Inc. See the Full Prescribing Information for more complete information. Tamoxifen may also be the active ingredient in other medications, and this information may not be accurate for all medications that include the active ingredient tamoxifen.