Testosterone levels decrease as you get older, dropping about 1-2% each year starting around age 40. In the U.S., around five million men have low testosterone or male hypogonadism.
In the past, testosterone replacement therapy (TRT) was the main treatment for low testosterone, but it has some harmful potential side effects, including testicular shrinkage, mood changes, and severe acne. Many of these side effects occur because TRT bypasses your body’s natural hormone regulation.
Enclomiphene, however, stimulates your body’s natural testosterone production instead of directly adding testosterone. It works with your body’s natural feedback systems, reducing health risks and side effects. Enclomiphene can help restore your natural testosterone production while preserving your fertility options.
Enclomiphene citrate acts as an estrogen antagonist. It blocks estrogen receptors, preventing estrogen from binding to them. This estrogen block is essential for men with low testosterone, as high estrogen levels can hinder the body’s natural testosterone production.
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How Enclomiphene Works to Increase Testosterone Levels
Enclomiphene operates by raising the levels of two crucial hormones, LH (luteinizing hormone) and FSH (follicle-stimulating hormone), which play a vital role in testosterone production. By acting as an estrogen antagonist, enclomiphene disrupts the negative feedback loop that typically inhibits the production of LH and FSH. This disruption results in elevated LH and FSH levels, stimulating the testes to produce more testosterone.
The distinctive mechanism of action of enclomiphene distinguishes it from traditional TRT methods. Instead of directly introducing external testosterone into the body, enclomiphene encourages the body’s innate testosterone production. This approach offers several advantages, including a more balanced approach to hormone regulation and fertility preservation.
Is Enclomiphene Safe?
Enclomiphene safety and effectiveness have been examined in a series of scientific studies. For instance, a study published in the National Library of Medicine examined the effects of both clomiphene and enclomiphene. The results found that adverse effects occurred less with the use of enclomiphene.
Regulatory Pathway
Enclomiphene has been under review by the U.S. Food and Drug Administration (FDA) since 2007. Initially, it was not approved for treating male hypogonadism because the FDA considered an increase in testosterone levels alone as insufficient evidence to establish enclomiphene as a suitable non-testosterone treatment for hypogonadism.
The denial of approval was based on a lack of evidence linking increased testosterone levels to meaningful improvements in the signs and symptoms of hypogonadism.
The FDA also rejected increases in LH and improved quality of life as indicators for enclomiphene use. Instead, the FDA sought evidence regarding enclomiphene’s potential to increase male fertility and address obesity-associated hypogonadism. In 2015, a scheduled meeting to review the evidence for enclomiphene as a treatment for low testosterone in men was canceled due to procedural concerns during report filing.
A follow-up presentation in 2022 addressed some of the FDA’s concerns. Marwa Elsaid, PharmD, stated that enclomiphene addresses patients’ unmet need for therapy that doesn’t compromise fertility. Unlike testosterone replacement therapy (TRT), which carries risks such as supranormal testosterone levels, suppression of sperm production, suppression of testicular function, and testicular atrophy, enclomiphene does not increase these risks. Despite this, the Pharmacy Compounding Advisory Committee voted against including enclomiphene on the 503A Bulks List.
Although enclomiphene is not approved for hypogonadism, both the American Urological Association and the European Association of Urology support the off-label use of clomiphene as a treatment for men with hypogonadism who wish to preserve their fertility.
Enclomiphene Side Effects
Though adverse reactions from enclomiphene may be less frequent than other treatment methods, side effects are still possible. These include side effects such as depressive thoughts, weak muscle strength, mood changes, and gynecomastia. It is also crucial to understand that enclomiphene treatment may not be suitable for everyone. Before starting any new medication, it’s essential to weigh the potential risks and benefits carefully.
If you are at an increased risk for stroke or blood clots, your risk of experiencing adverse effects from enclomiphene may be higher. Your doctor will assess your family history and conduct a blood hematocrit test to measure the proportion of red blood cells in your blood. High hematocrit levels may elevate your risk of blood clots when taking enclomiphene.
Who Can Benefit from Enclomiphene Treatment?
Enclomiphene treatment is suitable for men who have been diagnosed with low testosterone levels (below 250 to 300 ng/dl) and are experiencing symptoms associated with low testosterone levels.
Consulting with a healthcare professional who specializes in hormone therapy is essential to determine if enclomiphene is the right treatment option for you. They will take into consideration your health history, symptoms, and treatment goals to provide personalized recommendations that prioritize your overall well-being.
The Enclomiphene Treatment Process
If you and your healthcare professional decide that enclomiphene treatment is the right choice for you, the treatment process typically involves the following steps:
1. Initial Assessment and Diagnosis
Your healthcare professional will conduct a comprehensive assessment, which includes reviewing your medical history, discussing your symptoms, and evaluating any existing conditions. They may also perform blood tests to measure your testosterone levels and assess other hormone markers. To qualify for the diagnosis of hypogonadism, you must have symptoms indicative of low testosterone levels, along with morning testosterone levels below 250 to 300 ng/dL.
2. Treatment Plan Development
Based on the assessment results, your healthcare professional will create a personalized treatment plan. This plan will detail the recommended dosage, the duration of treatment, and any additional measures to monitor your progress. In most cases, your healthcare provider will order a hematocrit level before you start enclomiphene treatment to ensure it is below a threshold that may increase your risk of blood clots. During the first year of treatment, they may periodically check your hematocrit levels to verify that enclomiphene is not causing unhealthy elevations.
3. Enclomiphene Administration
Enclomiphene is typically administered orally as a tablet. Your healthcare professional will provide clear instructions on how to take the medication, including the recommended dosage and timing.
4. Monitoring and Adjustments
Throughout the treatment period, your healthcare professional will closely monitor your progress through regular follow-up appointments and blood tests. This ongoing monitoring allows them to assess the treatment’s effectiveness and make any necessary adjustments to optimize your hormone levels.
5. Evaluation of Results
After completing the recommended treatment duration, your healthcare professional will evaluate the results of the enclomiphene treatment. They will assess your symptoms, hormone levels, and any other relevant markers to determine the overall effectiveness of the treatment.
