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How Enclomiphene Works: Understanding Its Mechanism In Testosterone Regulation

Enclomiphene works by blocking estrogen receptors in the brain, increasing the release of gonadotropin-releasing hormone (GnRH)luteinizing hormone (LH), and follicle-stimulating hormone (FSH), which stimulate testicular testosterone production. It is a non-steroidal selective estrogen receptor modulator (SERM) used to treat male hormonal imbalances, specifically secondary hypogonadism.(1 ;2 ) Enclomiphene boosts natural testosterone production while preserving fertility. It can significantly increase testosterone levels within the normal physiological range, with dosage and individual factors influencing the degree of increase. Enclomiphene is taken orally, and adherence to the prescribed dosage and schedule is crucial for effectiveness. It typically takes a few weeks to notice hormonal changes, and enclomiphene should be purchased from reputable pharmacies with a prescription. Consulting with a healthcare professional is essential for proper use and management of potential side effects.

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Enclomiphene is perhaps best known under its brand name Androxal. It is a significant advancement in the treatment of secondary hypogonadism in men and primarily focuses on elevating serum total testosterone levels while maintaining normal sperm counts at the same time.

This prescription medication is a non-steroidal selective estrogen receptor modulator, which can provide a potential alternative to some of the traditional testosterone replacement therapies that are currently available. Many of these have the negative effect of suppressing spermatogenesis.

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The development of enclomiphene has been closely monitored by the medical community, especially following the FDA’s Complete Response Letter in 2015, which indicated that the drug could not be approved in its present form at that time. Today, we will take a look into what enclomiphene is used for, its mechanism of action, dosage guidelines, side effects, interactions with other drugs, and warnings and precautions that you should be aware of.

What is Enclomiphene?

Enclomiphene is a pharmaceutical medication that is classified as a non-steroidal selective estrogen receptor modulator (SERM). Chemically, it is derived from one of the isomers of clomiphene citrate, which has been used in the past for the treatment of female infertility. However, enclomiphene is focused more specifically on the treatment of male hormonal imbalances, particularly secondary hypogonadism.

Enclomiphene works by blocking estrogen receptors in the brain. This results in an increase in the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus, increased secretion of luteinizing hormone (LH), and follicle-stimulating hormone (FSH) from the pituitary gland, which in turn plays a role in stimulating testicular testosterone production. It allows enclomiphene to raise serum testosterone levels while still preserving, or even enhancing, sperm production and fertility levels, which are often decreased when using traditional testosterone replacement therapies.

What Does Enclomiphene Do?

Enclomiphene works by directly influencing the hormonal feedback mechanism within the body, which primarily targets the estrogen receptors located in the hypothalamus. The hypothalamus is an important part of the brain that is responsible for hormone regulation. By antagonizing these receptors, enclomiphene works to disrupt the normal negative feedback loop that estrogen has on the production of gonadotropin-releasing hormone.

This disruption results in an increased secretion of GnRH, which then stimulates the pituitary gland, sending a signal to release higher levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These hormones are essential for the stimulation of the testes in males, which can lead to an increased production of testosterone and can also play a role in helping to maintain the level of sperm production.

Unlike other traditional testosterone therapies that only replace testosterone, enclomiphene works differently. It boosts the body’s natural testosterone production, which is crucial for maintaining the balance between testosterone replacement and ensuring the preservation of fertility.

The increase in natural testosterone production can be especially beneficial for men with secondary hypogonadism, a condition where the issue lies not in the testes themselves but in the brain’s ability to regulate testosterone production properly.

What is Enclomiphene Used For?

Enclomiphene is usually used for treating men with secondary hypogonadism, a condition characterized by low testosterone levels due to problems originating from the hypothalamus or pituitary gland rather than the testes themselves. This condition often shows symptoms such as decreased libido, fatigue, muscle loss, and infertility, which can significantly impact a man’s overall quality of life.

One of the key benefits of enclomiphene is its ability to increase serum testosterone levels while simultaneously maintaining, or in some cases improving, sperm count and overall reproductive health.3 This dual functionality of the drug sets it apart from traditional testosterone replacement therapies. These typical therapies often suppress the body’s natural hypothalamic and pituitary activity, which can lead to a decrease in sperm production and potentially even infertility.

Enclomiphene stimulates the body’s natural testosterone production by antagonizing estrogen receptors in the brain.4 This antagonism reduces the estrogenic feedback inhibition on the hypothalamus. This process can help to increase the release of gonadotropin-releasing hormone. This increase in GnRH levels then promotes the secretion of luteinizing hormone and follicle-stimulating hormone from the pituitary gland, which in turn enhances testicular testosterone production and supports the generation of new sperm.

The medical use of enclomiphene is especially valuable for men who want to improve their testosterone levels without compromising their fertility. This medication is a promising alternative for anyone who is looking for treatment for symptoms that are associated with low testosterone due to secondary hypogonadism, including mood disturbances, decreased bone density, and sexual dysfunction.

How Much Does Enclomiphene Raise Testosterone?

Enclomiphene has been shown to have a considerable effect in raising testosterone levels in men diagnosed with secondary hypogonadism. Clinical studies have shown that taking enclomiphene can result in a significant increase in serum testosterone levels, which can address the core hormonal imbalance in those that are affected.

Research indicates that enclomiphene can increase testosterone levels to within the normal physiological range. For example, clinical trials have reported that dosages of 12.5 mg and 25 mg of enclomiphene citrate can significantly elevate total testosterone levels in hypogonadal men.5 These increases are often comparable to or exceed those achieved with topical testosterone applications, while also having the advantage of maintaining fertility. Enclomiphene has been documented to increase testosterone levels by approximately 50% to 100% from baseline in most patients, effectively doubling their testosterone levels in some cases. The degree of increase can vary based on several factors, including the individual’s baseline hormone levels, age, body mass index (BMI), and overall health condition.

How to Take Enclomiphene

Enclomiphene is administered orally and is primarily prescribed to treat secondary hypogonadism in men by raising their testosterone levels while also preserving their sperm count. It’s very important for patients to strictly stick to the prescribed dosage and schedule to ensure the drug’s effectiveness and minimize any potential risks or side effects.

The typical dosages of enclomiphene are 12.5 mg and 25 mg tablets. The appropriate dose varies based on individual factors such as the level of the testosterone deficiency, the response to the treatment, and any other underlying health conditions. Doctors usually start by prescribing the lowest effective dose and may adjust it depending on how the patient responds to therapy.

Enclomiphene should be taken once daily. For best results, it is recommended to take the medication at the same time each day to maintain steady hormone levels. Consistency in the timing of the dosage will help the body adjust to the new regimen and optimize the overall hormonal response.

The duration for which enclomiphene is usually prescribed can vary from person to person. Some men may need to take the medication for several months, while others might require a longer-term treatment. The continuation of treatment depends on the individual’s hormonal levels, the improvement of their symptoms, and their overall health. Receiving regular monitoring through blood tests is essential in order to assess the effectiveness and adjust the treatment if necessary.

Adhering to the prescribed enclomiphene regimen is crucial. Deviating from the advised dosage or schedule can significantly alter the effectiveness of the treatment. Overdosing can lead to increased risks of side effects such as mood swings, acne, or possibly more severe health issues, while underdosing might not adequately treat the testosterone deficiency.

Patients should never adjust their dosage without consulting their healthcare provider. Abruptly stopping the medication can also cause levels of testosterone to fall very quickly, which might lead to an influx of symptoms. Regular consultations and follow-up appointments with a healthcare provider will go a long way to helping ensure that any potential side effects are managed right away and adjustments to the treatment plan are made based on detailed health evaluations.

Ignoring medical advice or altering the treatment plan without speaking to a health care professional first could lead to hormonal imbalances that might affect mental health, physical health, and even overall quality of life.

How Long Does Enclomiphene Take to Work?

The length of time that it can take for enclomiphene to begin elevating testosterone levels can vary between patients depending on several individual factors. Patients may begin to notice an increase in testosterone levels within a few weeks of starting treatment. Clinical studies have shown that significant hormonal changes are typically noticeable within two to six weeks.

There are also many factors that can influence the speed and effectiveness of enclomiphene, which include the patient’s baseline testosterone levels, age, body weight, overall health, and the specific dosage prescribed. Men with extremely low initial testosterone levels may have a faster improvement, and younger individuals might also experience quicker results due to a more responsive hormonal system compared to older adults.

The patient’s metabolic rate and the body’s ability to absorb and process the medication also play important roles in how quickly enclomiphene takes effect. Sticking to the prescribed regimen by taking the medication consistently at the same time each day without missing a dose, and taking it exactly how it is prescribed will help maximize its effectiveness.

Where Can I Buy Enclomiphene Citrate?

Enclomiphene citrate is available for purchase primarily through a prescription from licensed healthcare providers. To obtain enclomiphene legally, patients must first speak with a healthcare professional who can provide a diagnosis and determine if enclomiphene citrate is the right treatment option for their condition. After a proper physical and bloodwork analysis, the doctor will then issue a prescription.

When looking to purchase enclomiphene citrate, it is very important to use a reputable pharmacy. Patients have the option of buying the medication from traditional brick-and-mortar pharmacies or through verified online pharmacies. In either case, it is essential to ensure that the pharmacy is properly licensed in the jurisdiction where it operates. Websites like the National Association of Boards of Pharmacy in the United States provide a list of accredited online pharmacies that meet safety and regulatory standards.

To avoid any type of counterfeit product, patients should be highly aware of outlets that offer enclomiphene without a prescription, sell the medication at a price that is significantly lower than the going rate, or do not provide adequate contact information on their website. Counterfeit drugs may not only be ineffective but also very harmful to your health.

Patients should also take into consideration the storage and shipping conditions that are offered by the pharmacy that they use to ensure that the medication maintains its efficacy. Always inspect the packaging for signs of tampering or damage upon receiving it and confirm that the product details match what was prescribed by the healthcare provider. By following these guidelines, patients can safely purchase enclomiphene citrate and avoid all of the risks that are associated with counterfeit medications.

Enclomiphene’s Role in Hormonal Health

Enclomiphene is an important treatment option for men who have secondary hypogonadism. It is unique in the way that it provides a method to effectively increase testosterone levels while also potentially preserving fertility at the same time. It stimulates natural testosterone production, which differentiates it from the traditional testosterone replacement therapies that are available on the market today.

As with any prescription medication, it is very important that you consult with a healthcare professional before starting enclomiphene. Doing so will ensure the treatment is appropriate for your specific condition and will help you manage any potential side effects. Always make sure that you get enclomiphene through legitimate channels and follow the prescribed guidelines to achieve the best possible outcomes.

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[2] Sizar O, Schwartz J. Hypogonadism. (Updated 2022 Jun 27). In: StatPearls {Internet}. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532933/;

[3] Rodriguez KM, Pastuszak AW, Lipshultz LI. Enclomiphene citrate for the treatment of secondary male hypogonadism. Expert Opin Pharmacother. 2016 Aug;17(11):1561-7. doi: 10.1080/14656566.2016.1204294. Epub 2016 Jul 4. PMID: 27337642; PMCID: PMC5009465.;

[4] Patel AS, Leong JY, Ramos L, Ramasamy R. Testosterone Is a Contraceptive and Should Not Be Used in Men Who Desire Fertility. World J Mens Health. 2019 Jan;37(1):45-54. doi: 10.5534/wjmh.180036. Epub 2018 Oct 10. PMID: 30350483; PMCID: PMC6305868.;

[5] Wiehle R, Cunningham GR, Pitteloud N, Wike J, Hsu K, Fontenot GK, Rosner M, Dwyer A, Podolski J. Testosterone Restoration by Enclomiphene Citrate in Men with Secondary Hypogonadism: Pharmacodynamics and Pharmacokinetics. BJU Int. 2013 Jul 12;112(8):1188–200. doi: 10.1111/bju.12363. Epub ahead of print. PMID: 23875626; PMCID: PMC4155868.;