Enclomiphene: The Game-Changing Alternative for Low Testosterone

March 25, 2024
Male symbol on a white pill with a blue background for low testosterone

Testosterone levels decrease as you get older, dropping about 1-3% each year starting around age 30 (1, 2). In the U.S., around five million men have low testosterone. When over 2,000 men aged 45 or older were tested, about 40% had low testosterone and its associated symptoms (3). However, only 1 in every 20 men with this condition receives treatment (2, 4).

Conditions like obesity, type 2 diabetes, and metabolic syndrome become more common as you age and can raise your risk of having low testosterone. If your testosterone levels fall below 300 nanograms per deciliter (ng/dl) on two morning measurements and you experience symptoms of low testosterone, your doctor may diagnose you with male hypogonadism, which means your testes don’t produce enough testosterone.

In the past, testosterone replacement therapy (TRT) was the main treatment for hypogonadism or low testosterone, but it has some harmful side effects, including testicular shrinkage, mood changes, and severe acne. This happens because TRT bypasses your body’s natural hormone regulation.

Enclomiphene, on the other hand, stimulates your body’s natural testosterone production instead of directly adding testosterone. It works with your body’s natural feedback systems, resulting in fewer health risks and side effects. Enclomiphene can help restore your natural testosterone production while preserving your fertility options.

Understanding Testosterone and its Importance

Testosterone is the main male sex hormone that plays crucial roles in various bodily functions. It’s responsible for developing male secondary sex characteristics like a deeper voice, facial hair growth, and building muscle mass. Testosterone also affects libido, sexual function, mood, and overall well-being, and it’s essential for sperm production.

The production of testosterone happens in the testes, and it can be transformed either systemically or locally into dihydrotestosterone (DHT) or estradiol by specific enzymes. Testosterone and DHT can inhibit their own production, but estrogen is the primary regulator. Blocking estrogen’s effects or its production can lead to increased testosterone production, as the pituitary gland responds by stimulating more testosterone (4).

Testosterone is produced in the testes in response to signals from the pituitary gland, particularly luteinizing hormone. If there’s an issue with the testes producing testosterone, it’s called primary hypogonadism. If the problem lies in the pituitary gland not signaling correctly, it’s known as secondary hypogonadism (5).

For primary hypogonadism, testosterone replacement therapy is the only treatment option. Secondary hypogonadism has more available treatment options (4).

Secondary hypogonadism becomes more common with age, obesity, metabolic syndrome, cardiovascular disease, liver disease, chronic kidney disease, and type 2 diabetes. The European Male Aging Study (EMAS) found that secondary hypogonadism is strongly linked to obesity (BMI >30), and the risk increases if men become overweight (BMI 25-30) (1).

Men with obesity have lower serum total and free testosterone levels than those at a healthy weight due to higher aromatase levels in fat tissue, which converts testosterone to estradiol (4).

Testosterone levels also tend to decrease with age, leading to various signs and symptoms like low sex drive, erectile dysfunction, reduced fertility, fatigue, increased abdominal fat, anemia, breast discomfort, hot flashes, and decreased muscle mass. Low testosterone is also associated with depression, osteoporosis, fractures, high blood pressure, abnormal blood lipids, and frailty (3).

Here are some signs and symptoms of low testosterone:

Sexual:

  • Decreased sex drive or low libido
  • Reduced sperm count
  • Erectile dysfunction (difficulty getting or maintaining an erection suitable for penetration)
  • Muscle loss

Neurologic/Psychiatric:

  • Mood changes
  • Difficulty concentrating
  • Decreased motivation
  • Decreased self-confidence
  • Decreased energy

Physical:

  • Decreased energy levels
  • Swollen or tender breasts (gynecomastia)
  • Hot flashes
  • Decreased physical strength
  • Decreased muscle mass
  • Increased body fat
  • Anemia

The decline in testosterone can significantly affect a man’s quality of life (5). This is where enclomiphene offers an alternative treatment option.

Enclomiphene: The Game-Changing Alternative for Low Testosterone

How do you diagnose low testosterone?

If you’re experiencing symptoms of low testosterone, the next step is to get your testosterone levels checked. The testing should ideally be done in the morning, specifically between 8 am and 10 am. If you’re a shift worker, it’s recommended to have your testosterone levels checked within two hours of waking up.

Your doctor may also request the following laboratory tests (7):

  • Sex hormone-binding globulin (SHBG): Testosterone circulates in the blood, either bound to sex hormone-binding globulin, bound to the protein albumin, or unbound. Only the free testosterone plus the testosterone bound to albumin is available to act on target tissues. Checking free testosterone and SHBG levels helps determine the amount of biologically active testosterone.
  • Luteinizing hormone (LH) and follicle-stimulating hormone (FSH): LH and FSH are hormones produced by the pituitary gland. LH stimulates the testes to produce testosterone, and FSH plays a role in sperm production. Measuring these hormone levels can help differentiate between low testosterone resulting from an issue in the brain or pituitary gland versus one in the testes.
  • Prolactin: Prolactin is a hormone produced by the pituitary gland that stimulates milk production. Abnormal prolactin levels can indicate a problem in the pituitary gland.

Additionally, there are some other lab tests your doctor may request (7):

  • Hemoglobin or hematocrit level: This checks your red blood cell count.
  • Lipid panel: This assesses your cardiovascular risk.
  • Prostate-specific antigen: This is used for screening for prostate cancer.
  • Baseline level of free estrogen: As testosterone levels rise, some of it can convert to estrogen. A baseline measurement of highly sensitive estrogen helps determine the rate of this conversion.

What is Enclomiphene?

Clomiphene citrate is a medication that consists of two components: zuclomiphene citrate and enclomiphene citrate. It falls into the category of non-steroidal selective estrogen receptor modulators (SERMs) and has been prescribed since the 1960s to address ovarian dysfunction in women (4).

Zuclomiphene citrate functions as an estrogen receptor agonist, meaning it binds to estrogen receptors and stimulates them to release estrogen. Zuclomiphene has a long-lasting effect, which can persist for 30 days or even longer. This means that any side effects induced by the medication may continue for weeks, even after discontinuing clomiphene.

Enclomiphene citrate, on the other hand, acts as an estrogen antagonist. It blocks estrogen receptors, preventing estrogen from binding to them. This is particularly relevant for men with low testosterone, as high estrogen levels can hinder the body’s natural testosterone production.

SERMs like enclomiphene also attach to estrogen receptors in the brain’s hypothalamus. By doing so, they prevent estrogen from binding to these receptors, allowing for the production of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These hormones, in turn, stimulate the testes to produce more testosterone (8).

Enclomiphene maintains FSH and LH levels and has a significantly shorter half-life (around 10 hours) compared to zuclomiphene. It not only raises testosterone levels but also preserves or even enhances sperm counts. This understanding led researchers to speculate that enclomiphene treatment could increase testosterone levels and maintain fertility in men with low-T.

Enclomiphene can be especially beneficial for men with low testosterone levels and obesity. This is because adipose (fatty) tissue contains aromatase, an enzyme that converts testosterone to estrogen (9). Enclomiphene helps decrease estrogen levels and boost testosterone, addressing the hormonal imbalance.

Enclomiphene: The Game-Changing Alternative for Low Testosterone

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, subsequently stimulating the testes to produce more testosterone (8).

The distinctive mechanism of action of enclomiphene distinguishes it from traditional testosterone replacement therapy (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 the preservation of fertility.

Clinical Trials Testing Enclomiphene Safety and Efficacy

Enclomiphene safety and effectiveness have been thoroughly examined in a series of scientific studies.

Initial Studies: In the initial safety studies for enclomiphene, baboons were divided into groups receiving either zuclomiphene, enclomiphene, or clomiphene. While zuclomiphene did not significantly increase testosterone levels, both enclomiphene and clomiphene did.

Among these groups, baboons receiving enclomiphene experienced the most substantial increases in testosterone levels, jumping from 170 ng/dl to 1,144 ng/dl. Notably, those receiving zuclomiphene had a 22% increase in total cholesterol levels, while those on enclomiphene saw an 8% decrease (9).

Phase II Studies: In the subsequent study, 12 men with hypogonadism (showing symptoms and lab evidence of low testosterone) were given either enclomiphene or testosterone. Both groups displayed significant and sustained increases in testosterone levels.

Furthermore, men taking enclomiphene showed elevated LH and FSH levels, along with increased sperm counts. Although this study involved a small group, the results were highly promising, suggesting that enclomiphene could boost testosterone levels in men with low-T while preserving fertility (10).

In another study, 73 men with hypogonadism received either testosterone or enclomiphene (12.5 mg or 25 mg). The testosterone group saw a significant increase in testosterone levels but a decrease in LH and FSH. Meanwhile, men on enclomiphene experienced increases in sperm density, FSH and LH levels, and sperm count.

Adverse events in this study included issues such as difficulty climaxing and loss of sensation during intercourse (leading to discontinuation of treatment), mild nausea, dry heaving (also leading to discontinuation of treatment), slightly increased estradiol, mild sinus headaches, and moderate headaches (11).

Phase III Studies: In a 2015 study involving 265 overweight men with hypogonadism aged 18-60, participants were given testosterone gel, enclomiphene citrate, or a placebo. Men receiving either testosterone or enclomiphene achieved testosterone levels within the normal range.

Those on enclomiphene experienced a 12% to 15% increase in sperm count, while the testosterone group saw a significant decrease. Reported adverse events included increased triglycerides and anxiety in men taking the 12.5 mg dose, and high hematocrit and high prostate-specific antigen (PSA) in men taking the 25 mg dose. Elevated hematocrit or PSA is considered an adverse event for enclomiphene, resulting in treatment discontinuation (12).

In a 2023 study, researchers compared the effectiveness of clomiphene citrate to enclomiphene citrate in treating men with low testosterone levels, infertility, and abnormal sperm counts. Both medications increased serum testosterone levels, but only enclomiphene increased FSH and LH levels. Sperm motility increased in both groups, but total sperm count only increased in those who received enclomiphene. Enclomiphene also significantly raised estradiol levels, although the significance of this finding is unclear (13).

In a safety study registered at ClinicalTrials.gov (NCT01534208), men received either 12.5 mg or 25 mg of enclomiphene citrate for 26 weeks. The following adverse events were reported (with one report per event in most cases):

  • slow heart rate
  • chest pain
  • abdominal pain
  • transient ischemic attack (TIA)
  • seminoma
  • shortness of breath
  • knee arthroplasty
  • deep vein thrombosis (blood clot) in two cases
  • low blood pressure
  • abnormal heart rhythm
  • gallstones
  • diverticulitis
  • food poisoning
  • kidney infection
  • pulmonary embolism
  • cellulitis (skin infection) in two cases

Additionally, non-serious adverse events reported in phase 2 and phase 3 enclomiphene clinical studies included:

  • hot flushes (1.1%)
  • muscle spasms (0.9%)
  • headache (1.6%)
  • dizziness (0.7%)
  • blurred vision (0.5%)
  • nausea (1%)
  • fatigue (0.6%)
  • increased hematocrit (0.6%)
  • erectile dysfunction (0.6%)
  • PSA increased (0.6%)
  • aggression (0.5%)
  • irritability (0.5%)
  • acne (0.5%)
testosterone levels

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 (11).

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 subsequent evaluation by both the FDA and the European Medicines Agency (EMA) in 2018 examined enclomiphene. The EMA Assessment Report concluded that enclomiphene’s safety had not been sufficiently demonstrated. The FDA expressed concerns about heart events, blood clots, elevated estradiol levels, increased PSA, and higher hematocrit levels. Consequently, the FDA voted against including enclomiphene citrate in the 503A Bulks List.

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 (13,14).

Currently, enclomiphene is prescribed off-label to treat hypogonadism (4). Off-label prescribing is legal and common, indicating that licensed medical professionals have evaluated the risks and benefits of using a particular medication to treat a specific medical condition and have deemed it appropriate.

Expert Opinion: “Enclomiphene citrate, while incompletely studied, is effective in ameliorating testosterone deficiency and maintaining semen quality, with few apparent adverse effects.” KM Rodriguez et al. in Expert Opinion in Pharmacotherapy.

Enclomiphene Side Effects

Reported most frequent enclomiphene side effects include:

  • Headache
  • Hot flushes
  • Stomach discomfort
  • Nausea
  • Muscle spasms

Enclomiphene citrate is contraindicated in individuals who fall into any of the following groups:

  • Pregnant or breastfeeding
  • Unexplained uterine bleeding
  • Ovarian cysts or growths unrelated to polycystic ovarian syndrome
  • History of liver disease
  • Uncontrolled adrenal or thyroid disease
  • Known allergy to enclomiphene or clomiphene

Further research is needed to determine a complete enclomiphene side effects profile and how it compares to testosterone replacement therapy.

Testosterone Replacement Therapy

Testosterone replacement therapy (TRT) has been the standard treatment for hypogonadism. However, it has some drawbacks, such as suppressing the release of FSH and LH, negatively impacting male fertility. There are various delivery methods for TRT, each with its own advantages and disadvantages.

Testosterone Injections

Testosterone injections are available in different forms, including testosterone cypionate (Depo-Testosterone), testosterone enanthate (Xyostad), and testosterone undecanoate (Aveed). The frequency of administration varies. Typically, they are delivered through intramuscular injections, although there is also a subcutaneous version of testosterone enanthate.

Buccal Testosterone

Buccal testosterone is presented in the form of a tablet-shaped pouch with a putty-like consistency. It is placed between the upper lip and gum and slowly absorbed through the mouth’s lining.

Testosterone Pellets

Testosterone pellets are implanted under the skin, providing a slow release of testosterone over several months. The procedure is performed in a medical office, and infections and scarring are rare side effects.

Testosterone Patches

Testosterone patches are applied to non-hairy areas of the skin, left in place for 24 hours, and then replaced. The same area can only be reused after at least seven days. Patches may cause blisters, redness, pain, or itchiness at the application site.

Testosterone Gels

Testosterone gels are absorbed through the skin and applied once daily in the morning. The application site depends on the manufacturer. However, a major concern with testosterone gels is the potential for accidental transfer to women and children, leading to serious health risks. As a result, these gels carry a boxed warning from the FDA.

Testosterone Nasal Gels

Natasto is a nasal gel FDA-approved in 2014. Testosterone is rapidly absorbed from the inside lining of the nose and is typically applied every six to eight hours or as directed by a doctor.

Testosterone Pills

In addition to the above options, an oral pill form of testosterone undecanoate was approved by the FDA in March 2019. However, it comes with a boxed warning for potentially causing high blood pressure. The FDA has only approved this option for men with low testosterone due to a medical condition, not age-related low-T. According to the FDA, the risk of high blood pressure outweighs the benefits for age-related low-T treatment.

A well fit man showing off his biceps

Enclomiphene vs. Traditional Testosterone Replacement Therapy

Enclomiphene offers several distinct advantages over traditional TRT methods, such as testosterone injections or gels/creams. As the prevalence of symptomatic low testosterone increases with age and weight gain, enclomiphene provides an option for men to restore their testosterone levels while maintaining their fertility.

1. Fertility-Friendly Approach. One of the significant concerns with traditional TRT is its impact on fertility. TRT can suppress sperm production and decrease sperm quality, making it challenging for men to conceive.

It does so by boosting testosterone levels, which negatively affects the production of essential hormones like FSH and LH, crucial for sperm production.

It can take months or longer for sperm production to recover after discontinuing TRT, and in rare cases, FSH and LH production may never return to pre-TRT levels, permanently impacting fertility(15,16).

In contrast, enclomiphene promotes the body’s natural testosterone production without compromising fertility. This makes it an ideal choice for men looking to preserve or enhance their fertility while addressing low testosterone levels. Enclomiphene clinical studies have shown that it can increase testosterone levels and improve sperm motility and total sperm count.

2. Balanced Hormone Regulation. Traditional TRT can sometimes lead to fluctuating testosterone levels, resulting in highs and lows that may cause unwanted side effects(2). According to Harvard Health, testosterone levels can spike after an injection and then decline, leading to mood and energy fluctuations.

Enclomiphene helps restore a more balanced approach to hormone regulation by stimulating the body’s natural testosterone production, resulting in a more stable and consistent testosterone level, reducing the risk of hormonal imbalances.

3. Convenience and Ease of Use. Enclomiphene offers the advantage of convenience and ease of use. Unlike traditional TRT methods that require regular injections or the application of gels/creams, enclomiphene is taken orally, making it a simple and hassle-free addition to your daily routine. This eliminates the need for frequent medical appointments or complex administration procedures. Additionally, testosterone creams and gels can inadvertently transfer to other individuals, potentially causing side effects in women and children. Proper storage and precautions are necessary to prevent such transfer.

4. Safety Profile. Enclomiphene has demonstrated a favorable safety profile in studies, although further research is needed to fully understand its risk-benefit profile. It is generally well-tolerated, with the most common side effects being headache and stomach tenderness. An evaluation concluded that enclomiphene citrate was not considered toxic to the genome and did not increase the risk of cancer. Serious side effects are rare, making enclomiphene a safe and viable treatment option for men with low testosterone levels.

In contrast, TRT side effects can vary depending on the person and the method of testosterone delivery, and may include:

  • acne
  • oily skin
  • low sperm count
  • infertility
  • increased risk of blood clots
  • fluid retention
  • increased red blood cell production
  • sleep apnea
  • mood swings
  • irritability
  • breast tenderness
  • breast enlargement (gynecomastia)
  • skin reactions
  • injection site pain
  • testicular shrinkage

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.

However, it is crucial to understand that enclomiphene treatment may not be suitable for everyone. Before starting any new medication, it’s essential to carefully weigh the potential risks and benefits. 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.

It’s worth noting that both increased hematocrit and an increased risk of venous thromboembolism (blood clot) are known risks associated with testosterone replacement therapy and enclomiphene.

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 individual health history, specific 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.

A man lifting weights

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.

While there is limited research on what to expect after enclomiphene therapy, it’s worth noting the potential benefits of testosterone therapy and the estimated timeframes for experiencing these effects.

Benefit of Testosterone Replacement(17)Estimated Time to See This Effect
Increased insulin sensitivitya few days
Improved libido and erectile function 3 to 6 weeks
Increased energy, mood, and vitality3 to 6 weeks
Increased lean body mass12 to 16 weeks
Reduced abdominal fat mass12 to 16 weeks
Increased bone density6 months
Increased muscle strength12-16 weeks
Reduced blood glucose3 to 12 months

Lifestyle Factors to Support Testosterone Production

In addition to enclomiphene treatment, several lifestyle factors can support natural testosterone production. Incorporating these habits into your daily routine can further enhance the benefits of enclomiphene and contribute to overall well-being. Here are some key lifestyle factors to consider:

1. Regular Exercise and Physical Activity

Engaging in regular exercise and physical activity can have a positive impact on testosterone levels. In one study, resistance exercise training increased testosterone and 5α-dihydrotestosterone (DHT) levels in both younger and older men(18).

Increasing your daily exercise can burn more calories and help you lose excess weight. Increased muscle mass and decreased abdominal fat are both associated with higher testosterone levels. In one study, just six weeks of resistance exercise were enough to boost testosterone levels (19).

For individuals with overweight or obesity, resistance exercise can be even more beneficial. Obesity can lower testosterone levels, and researchers found that increased resistance exercise had a greater impact on testosterone levels than dietary changes alone (20).

Aim for a combination of cardiovascular exercise, strength training, and high-intensity interval training (HIIT) to optimize your overall health. If you don’t have access to a gym or equipment, bodyweight exercises like squats, planks, and push-ups can be effective. Consistency is key because the testosterone boost from each exercise session is short-lived.

2. Balanced Diet

Maintaining a balanced and nutritious diet is crucial for overall health and hormone production. Focus on consuming a variety of whole foods, including lean proteins, fruits, vegetables, whole grains, and healthy fats. Avoid excessive consumption of processed foods, sugary snacks, and unhealthy fats.

Protein is essential for building and repairing cells in the body, including hormone-producing cells. As you build muscle and use fat for energy, prioritize protein in your reduced-calorie diet.

To naturally regulate your hormones, include foods like:

  • fatty fish (salmon, tuna, mackerel)
  • leafy greens (spinach, kale)
  • avocados
  • eggs
  • pomegranates
  • oysters
  • onions
  • ginger in your diet

3. Adequate Sleep

Getting enough quality sleep is essential for proper hormone regulation, including testosterone production. The majority of daily testosterone release in men occurs during sleep. Fragmented sleep and obstructive sleep apnea can both increase the risk of lower testosterone levels (21).

Longer episodes of sleep deprivation have a greater impact on testosterone levels than shorter periods (22). In one study, just one week of sleep restriction to five hours per night decreased testosterone levels by 10% to 15% in young men(21).

Aim for 7-9 hours of uninterrupted sleep each night to support optimal testosterone levels. Here are some tips to improve sleep quality:

  • Stick to a consistent sleep schedule, even on weekends.
  • Keep your bedroom cool, dark, and quiet.
  • Remove technology from the bedroom.
  • Avoid caffeine, alcohol, heavy meals, and screens for several hours before bedtime.
  • Establish a pre-bedtime routine that is relaxing.
  • Get outside and expose yourself to natural sunlight in the morning to help set your circadian rhythm.

4. Stress Management

Chronic stress can negatively impact testosterone levels. Stress triggers increased cortisol release, which can directly inhibit testosterone production. Over time, chronic stress can lead to reduced testosterone levels(23).

Implement stress management techniques such as meditation, deep breathing exercises, yoga, or engaging in hobbies and activities that you enjoy and find relaxing.

5. Weight Management

Maintaining a healthy weight is important for testosterone production. Excess body fat, particularly around the abdomen, can contribute to hormonal imbalances. Focus on achieving and maintaining a healthy weight through a combination of regular exercise and a balanced diet.

BMI measurements

6. Cut Back on Alcohol

In one study, researchers isolated the impact of alcohol consumption on testosterone production by removing the effects of smoking habits, age, body mass index, and physical activity. Men who consumed over 40 grams of alcohol per day had the lowest total testosterone and sex hormone-binding globulin levels.

Low-to-moderate alcohol consumption may increase testosterone concentrations, while larger quantities are associated with decreased testosterone levels(24).

Conclusion

Enclomiphene offers an alternative for men with low testosterone, especially those who want to preserve their fertility. It stimulates your body’s natural testosterone production and works with your body’s natural feedback mechanisms. Unlike testosterone replacement therapy, enclomiphene has a fertility-friendly profile, allowing it to boost low testosterone while preserving your fertility.

If you are experiencing symptoms of low testosterone, it’s essential to consult with a healthcare professional at Invigor Medical or a similar healthcare provider. They can assess your individual needs, evaluate your symptoms, and conduct necessary tests to determine if enclomiphene treatment is the right choice for you. A healthcare professional can provide personalized guidance and help you make informed decisions about your treatment options.

Frequently Asked Questions

What does enclomiphene do for men?

Enclomiphene increases testosterone levels without affecting fertility. Unlike testosterone replacement therapy, enclomiphene does not override the natural feedback loop that controls testosterone production.

Is enclomiphene a steroid?

No, enclomiphene is not a steroid. It is a non-steroidal selective estrogen receptor antagonist. It blocks the effects of estrogen and increases testosterone production.

Is enclomiphene the same as Clomid?

Clomid is a mixture of two isomers: zuclomiphene and enclomiphene. Zuclomiphene is a weak estrogen agonist with a long half-life, and enclomiphene is an estrogen antagonist with a much shorter half-life.

Why was enclomiphene not approved?

The FDA stated that the design of the enclomiphene phase 3 studies was no longer adequate to show clinical benefit. They showed that enclomiphene increased testosterone levels but did not show how an increased testosterone level provided benefits such as increased muscle strength, improved sexual function, and decreased fatigue.

Does enclomiphene cause infertility?

No, one of the key advantages of taking enclomiphene instead of testosterone replacement therapy is that enclomiphene maintains a normal brain, pituitary, and testes axis. It increases testosterone production while maintaining normal follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels. In clinical studies, men taking enclomiphene maintained or increased their sperm motility and total sperm count.

Can enclomiphene increase blood clots?

Yes, enclomiphene can increase your hematocrit (the proportion of red blood cells in your bloodstream) and your risk for venous thromboembolism (blood clots). These are known risks when increasing testosterone levels. Have your hematocrit checked before starting enclomiphene and periodically after you begin taking the medication. If you have a family history of blood clots or risk factors for blood clots, discuss this increased risk with your doctor.

Is enclomiphene a form of TRT?

No, enclomiphene is an alternative to TRT. Like testosterone replacement therapy, enclomiphene is used to increase testosterone levels in men with hypogonadism. Hypogonadism is a condition in which the testes do not produce enough testosterone. It is diagnosed in men with symptoms that are consistent with low testosterone levels and documented morning testosterone levels below 250 to 300 ng/ml.

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