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The Benefits And Potential Side Effects Of Enclomiphene Therapy

Your hormones play a role in a wide variety of functions to help you live a happy and healthy life. However, as we age, there are a variety of different reasons that hormone levels can change. While many of these changes are a natural part of life, there are some others that happen as the result of health conditions, injuries, or other reasons.

Hormone therapies are now being used to help treat a wide variety of conditions, and the science has drastically improved outcomes for patients over the last twenty years. Enclomiphene, also referred to as enclomiphene citrate or by brand name as Androxal, is a non-steroidal medication used to raise testosterone levels in men while maintaining normal sperm counts.

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What is Enclomiphene?

Enclomiphene is closely related to clomiphene citrate, an FDA approved drug for the treatment of female ovulatory dysfunction. The two drugs are closely chemically related in their structure and properties.

Enclomiphene works by binding to estrogen receptors in the pituitary gland.1 This action stops the negative feedback that the receptor normally creates and stimulates the production of the hormone GnRH, or gonadotropin. In turn, this hormone stimulates the production of another hormone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH).

While closely related to clomiphene, enclomiphene differs in the chemical structure because it lacks the cis isomer, zuclomiphene. The lack of this isomer also reduces the half-life of the compound from 30 days to around 10 hours. This change may make it a more suitable approach for men experiencing hypogonadism and reduce potential side effects.

Benefits of Enclomiphene Therapy

Enclomiphene therapy has been a recent addition to potential therapies for men experiencing hypogonadism, and there are several potential enclomiphene citrate benefits for this treatment.

Enclomiphene can help boost testosterone levels by promoting the body to produce more of this hormone. It is commonly used to boost testosterone in males that experience secondary hypogonadotropic hypogonadism. This type of low testosterone level is caused by issues with hormones in the pituitary and hypothalamus. In contrast, primary hypogonadotropic hypogonadism is caused by defects in the testes that lead to lower production of testosterone.

Enclomiphene boosts testosterone levels in men by competing with estrogen to bind to the receptors. Blocking estrogen from being processed results in increased levels of gonadotropin, which in turn boosts other hormones to be produced, leading to increases of testosterone production. This approach is different than simply replacing testosterone from an external source, but instead allows the body to naturally produce more of its own testosterone.

Low levels of testosterone have also been linked with a variety of health and sexual issues in men, including low libido, and reduced motility in sperm. These two specific factors can have a negative impact on issues with fertility for men.

Sperm motility refers to how well sperm can move, which is a critical component in allowing for the fertilization of an egg during intercourse. Sperm that are less motile have a more difficult time reaching the egg for fertilization, resulting in lower rates of pregnancy. Low libido reduces the drive that men have to pursue sex and can lead to infrequent sexual encounters, also reducing the potential for pregnancy.

Enhanced Athletic Performance

Enclomiphene may also help enhance athletic performance due to its ability to increase the production of testosterone.2 Additionally, this medication can help with weight loss, so individuals can shed additional weight to help reach their health goals.

Enclomiphene testosterone increases may help to build and maintain muscle, libido, and overall health, all factors that can be utilized to help with athletic performance in many sports.

man working out with dumbbells

Enclomiphene has also been initially studied in the use of treating obesity and potentially type II diabetes. The ability of the drug to help with favorable effects on fasting plasma glucose suggest that it may be a key part of managing or achieving healthy weight for patients.

While a major emphasis for enclomiphene has been placed on men’s testosterone levels, there are also promising studies for women’s health. Through the same action of competing for estrogen receptors that increase gonadotropin release, women may see an improvement in regular ovulation schedules.

Potential Side Effects

As with any medication, there are always the risks of side effects.3 There are a variety of potential enclomiphene citrate side effects, but most of these are either infrequent or of limited concern.

Common Side Effects

Some of the common side effects of enclomiphene include headache, nausea, diarrhea, hot flashes, dizziness, arthralgia (joint pain), and Nasopharyngitis (a common cold).

Severe Adverse Reactions

Initial studies were concerned with a few more serious health reactions including venous thromboembolisms, but the study incidences were in the “very low” category and have not been considered a side effect of the medication. The additional serious side effects that were considered were actually lower than the placebo group, so these have also not been disclosed.

While most of the side effects associated with enclomiphene have been mild, there are some potentially more serious reactions that patients have had when taking the medication. These include some allergic reactions, ranging from hives, skin irritation, or rashes. However, some more serious issues have occurred that include numbness, tingling, or swelling of the tongue, lips, mouth, face, or throat that can lead to difficulty breathing.

Additional serious side effects include changes in vision, such as blurred vision or flashes of light. Patients have also experienced shortness of breath, tightness in the chest, and swelling in the legs. Leg swelling can be a sign of a blood clot. If somebody experiences any of these issues, it is important to seek medical attention immediately.

Interactions With Other Medications

Enclomiphene does have several mild to moderate interactions with other medications, so it is important to disclose all of your medications to your doctor during your consultation.

Precautions and Safety Measures

Enclomiphene isn’t the right choice for every individual. This medication has been designed and studied for use in individuals with secondary hypogonadotropic hypogonadism. There are several other off-label uses, but these should be discussed with your doctor before you begin taking the medication.

There are certain populations that should avoid taking enclomiphene. These include women who are pregnant or breastfeeding, have unexplained uterine bleeding, or have unexplained uterine cysts or growths that are not related to polycystic ovarian syndrome.

Additionally, patients who have a history of liver disease, uncontrolled adrenal or thyroid dysfunction, or a known allergic reaction to enclomiphene or clomiphene should avoid the medication.

When you first begin taking enclomiphene, it is important to monitor your body’s response to treatment. Some side effects can take place almost immediately, such as an allergic reaction. Allergic reactions that impact your ability to breathe require immediate medical intervention. These include numbness, tingling, or swelling to the face, throat, mouth, or tongue.

Additionally, long-term monitoring of the medication should be conducted by your health care professional to ensure that the medication is effective and that there are no long-term side effects that need to be addressed.

Emergency Symptoms And How To Respond

If you take enclomiphene and suffer from an emergency situation, such as a difficulty breathing, chest pain or tightness, or swelling in the legs, it is important to seek medical help immediately. Some of these issues can be the sign of potentially life-threatening conditions and should be taken seriously.


Currently, exogenous testosterone treatment is the primary treatment to help correct low testosterone counts in men. Several studies have indicated that enclomiphene is a viable option to increase testosterone levels to the normal range without negatively impacting sperm counts.

Enclomiphene may be a suitable alternative treatment for men who cannot use testosterone replacement therapy. Although treatments are generally well tolerated and safe for use, it is essential to speak with your doctor to determine if this treatment is right for you.

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[1] Estrogen receptor signaling mechanisms. Fuentes N.

[2] Testosterone restoration using enclomiphene citrate in men with secondary hypogonadism: a pharmacodynamic and pharmacokinetic study. Wiehle R.

[3] Enclomiphene Citrate for the Treatment of Secondary Male Hypogonadism. Rodriguez KM.

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