Enclomiphene Benefits for Men: Hormonal Health and More

Key Takeaways:

• Enclomiphene boosts natural testosterone production by stimulating the hypothalamic-pituitary-gonadal (HPG) axis, making it a promising alternative to testosterone replacement therapy (TRT).

• Unlike TRT, enclomiphene preserves fertility, since it raises LH and FSH rather than suppressing them. This factor can be a major advantage for men who are planning to have kids.

• Potential benefits of enclomiphene for men may extend beyond hormone balance, including support for sexual function, fertility, muscle mass, bone density, and mood, though more research is needed.
  

Though more research is needed about enclomiphene benefits for men, it has promise for becoming an alternative to testosterone replacement therapy (TRT). The drug may be a particularly interesting option for men who want to boost testosterone without lowering their sperm count, which is an effect of TRT.

Below, we’ll explain how enclomiphene works and how, for some men, increasing testosterone can improve other aspects of health, including cognitive health, body composition, and more.

Enclomiphene belongs to a class of drugs known as selective estrogen receptor modulators (SERMs). Unlike TRT, which shuts down testosterone production and pumps a synthetic version of the hormone into your system, enclomiphene kick-starts your body’s natural testosterone production by acting on the hypothalamic-pituitary-gonadal (HPG) axis.

Here’s how enclomiphene works:

• Enclomiphene binds to estrogen receptors in the hypothalamus, preventing negative feedback.

• This blocking effect prompts the pituitary gland to secrete more gonadotropins, specifically luteinizing hormone (LH) and follicle-stimulating hormone (FSH).

• LH then signals the Leydig cells in the testes to produce more testosterone, and FSH stimulates the Sertoli cells to make more sperm.

Enclomiphene is closely related to clomiphene citrate (Clomid^®), an FDA-approved medication for female infertility. Clomid is actually a mix of two isomers, or chemical compounds: enclomiphene and zuclomiphene. Enclomiphene is not approved by the Food and Drug Administration (FDA).

Both Clomid and enclomiphene are sometimes prescribed off-label for men with secondary hypogonadism, which is low testosterone caused by faulty signaling between the brain and testes. The problem is, Clomid’s zuclomiphene component can act like estrogen, leading to side effects such as hot flashes,  male breast growth (gynecomastia), and mood swings. Research suggests that most of Clomid’s benefits come from the enclomiphene portion, while zuclomiphene adds little beyond unwanted estrogenic side effects.

Studies comparing enclomiphene to exogenous testosterone show that both treatments increase testosterone to reach the normal range within two weeks. However, the two treatments have opposite effects on LH and FSH levels.

Unlike TRT, which suppresses LH and FSH levels, enclomiphene increases LH and FSH levels in addition to testosterone. Also notable is that after treatment stops, testosterone levels remain elevated in enclomiphene users for at least a week, while levels drop for TRT users.

Another study comparing enclomiphene therapy to topical testosterone therapy found that both treatments increased testosterone levels, but only enclomiphene maintained sperm concentrations in the normal range. Sperm counts declined in men taking topical testosterone.

Because enclomiphene boosts FSH levels, which signals the testes to produce more sperm, it’s possible that enclomiphene may increase sperm production and improve fertility.

In one small 2013 study that compared enclomiphene to testosterone gel in men previously treated with TRT, both treatments restored total testosterone levels to the normal range within six months, but only men taking enclomiphene experienced significantly elevated sperm counts.

Another study compared enclomiphene to clomiphene in men with low testosterone and infertility who were trying to achieve pregnancy with a female partner. Men taking enclomiphene had higher LH and FSH levels, while those on clomiphene had higher estradiol (estrogen) levels. Ultimately, couples were more likely to get pregnant when the male partner was on the enclomiphene treatment. 

Enclomiphene is still considered an investigational medication, so there’s a lot we don’t know about its long-term effects and how well it can impact other aspects of men’s health.

What we do know is that enclomiphene is effective at increasing low testosterone levels. And testosterone is a key hormone in reproductive health, sexual function, mental health, and more.

Here are some of the potential benefits of taking enclomiphene to raise testosterone levels — based on what we know about how the hormone works in the body.

Anti-Aging

Research on testosterone and aging has often framed the hormone as some sort of longevity tonic for strength, libido, and energy levels. But the evidence for testosterone therapy’s anti-aging benefits is mixed. It’s true that testosterone levels decline with age, and many men with testosterone deficiency who try therapy report feeling more energetic or younger. While this may hold anecdotal validity, know that direct anti-aging effects of TRT — or alternatives like enclomiphene — remain scientifically unproven.

Muscle Restoration

Testosterone plays a key role in building lean muscle mass by promoting protein synthesis and reducing protein breakdown. Studies in men support the notion that testosterone not only drives muscle growth but also boosts strength, and levels can rise acutely after a bout of heavy resistance training. However, the magnitude of this response depends on factors like age, sex, and the structure of the workout.

Whether enclomiphene can make you stronger or increase muscle mass is not yet known. But research on TRT and clomiphene can give us an idea of how muscles respond to increased testosterone levels.

For instance, one small 2022 study concluded that treatment stimulates muscle growth even during calorie deficits. A 2018 study found that men with hypogonadism and obesity gained lean muscle mass throughout 12 weeks of taking clomiphene (which contains enclomiphene).

However, enclomiphene isn’t a steroid, and there’s no medical literature that suggests the medication can be used in men with normal testosterone levels solely for performance enhancement.

Increased Bone Density

Low testosterone is a known risk factor for low bone density and conditions like osteopenia and osteoporosis.

In a small study of 46 hypogonadal men, clomiphene significantly raised testosterone levels and improved bone mineral density in men who were taking the medication for more than a year.

Other research has demonstrated that TRT can help maintain bone mineral density and protect against fractures in men with hypogonadism and low bone density.

Enclomiphene may offer similar bone-protecting benefits by increasing testosterone, but like the other benefits mentioned in this list, this hasn’t yet been the direct subject of research. More investigation is needed before we can say for sure.

Memory Retention

Studies show that sex hormones like testosterone play a crucial role in cognitive health.

Higher levels have links to sharper brain function and less buildup of certain proteins associated with Alzheimer’s disease. Low testosterone, on the other hand, has connections to memory loss and a higher risk of developing Alzheimer’s.

Testosterone may help protect the brain by supporting immune cells that clear out waste and reduce inflammation. Research also supports that testosterone therapy in men with low T may help cognitive performance, memory, and executive function.

However, there are conflicting results to support these claims.

This 2017 study showed that one year of testosterone treatment among older men with low testosterone and age-associated memory impairment didn’t result in improved memory or other cognitive functions.

Some animal research suggests clomiphene may also help clear proteins linked to Alzheimer’s and improve cognition, but more human research is needed to understand the full impact of clomiphene and enclomiphene on brain health.

Improved Sexual Function

Some of the most common symptoms of low testosterone are low libido and erectile dysfunction (ED).

Studies show that “normalizing” testosterone levels in men with low T at baseline can improve their libido and erectile function if ED symptoms are mild. Testosterone therapy is especially useful in men with hypogonadism and mild ED who don’t respond to typical ED medications like sildenafil or tadalafil. However, testosterone therapy may not work for men with moderate or severe ED, as the root cause may include other medical conditions like neurological damage or diabetes. There also doesn’t seem to be any added benefit of using TRT to improve sexual function once T levels have leveled.

Men using clomiphene have achieved similar results. In a small study of men with low testosterone and erectile dysfunction, clomiphene improved sexual function in 75 percent of participants. Men who didn’t respond as well were more likely to be older or have health issues such as diabetes, high blood pressure, or heart disease.

Again, more studies are needed to know how enclomiphene impacts symptoms of male hypogonadism, like low libido and ED.

In some cases, using enclomiphene and ED medication at the same time may provide a stronger benefit than either medication alone. Hims offers enclomiphene + tadalafil (the active ingredient in Cialis^®) to improve testosterone and erectile function simultaneously. To find out if you qualify for treatment, schedule a medical consultation to receive an at-home testosterone testing kit and discuss personalized treatment plans with a licensed healthcare provider. 

Enhanced Mood

Testosterone plays an important role in mood and mental health, and low levels have links to depression, anxiety, fatigue, and low quality of life.

Some studies suggest that raising testosterone with TRT can improve mood and ease depressive symptoms, possibly in part by restoring sexual function. However, when testosterone levels are pushed too high — such as in anabolic steroid use — negative effects like irritability, aggression, and anxiety can occur.

Because enclomiphene raises testosterone without pushing it to a range that’s way too high, it may offer mood-related benefits similar to TRT without the risks tied to excessive dosing. Still, more research is needed to understand enclomiphene’s full impact on mental health.

Enclomiphene is a treatment option for men with diagnosed secondary hypogonadism. The drug can be especially appealing for men who are planning to have kids, as — unlike TRT — enclomiphene won’t compromise fertility.

Though generally considered safe and well-tolerated, enclomiphene can cause side effects in some users and may not be suitable for those with certain health conditions.

Potential side effects of enclomiphene include:

• Headaches

• Nausea

• Dizziness

• Blurred vision

• Muscle spasms

• Hot flashes

• Increase in red blood cell count

Enclomiphene may also not be suitable for men with primary hypogonadism, a type of low testosterone that originates in the testes.

It’s also not recommended for men with normal testosterone levels, athletes seeking performance enhancement, or those with a preexisting risk of blood clots.

Read more about enclomiphene’s safety and side effects.

No, enclomiphene is not approved by the Food and Drug Administration (FDA), but it is one of the isomers in clomiphene, which is an FDA-approved medication for female infertility.

Enclomiphene is accessible via compounding pharmacies in the U.S., but you’ll need a prescription from a healthcare provider. Currently, the FDA does not approve or verify compounded drugs for safety, effectiveness, or quality, so your provider will need to prescribe enclomiphene to you off-label. You can read more about enclomiphene’s safety and side effects here.

Enclomiphene citrate is emerging as a promising alternative to testosterone replacement therapy for men with low testosterone levels. But can it do more than give your hormone levels a boost?

Here’s what we know:

• Enclomiphene supports your natural production of testosterone. Unlike TRT, which replaces your testosterone with a synthetic version of the hormone, enclomiphene stimulates the HPG axis, making it a potential alternative to TRT.

• Potential benefits may exceed higher hormone levels. Higher testosterone from enclomiphene may support fertility, sexual function, muscle mass, and even cognitive health, though much of the research is still early or indirectly supportive.

• Enclomiphene is best suited for men with secondary hypogonadism. It’s not a performance-enhancing drug for men with normal testosterone, and it’s currently not approved by the FDA. More studies are needed to confirm its long-term safety and effectiveness.

Want to learn more about how to support healthy testosterone production? Explore a full range of testosterone treatments through Hims, learn about our at-home lab testing, and schedule a consultation with a healthcare provider to see if enclomiphene is right for you. 

Also, learn tips and strategies on how to increase testosterone naturally, find out if testosterone boosters work, and explore the link between hypogonadism and ED.

Is enclomiphene as effective as testosterone replacement therapy (TRT)?

Studies show enclomiphene raises testosterone to normal levels just as effectively as TRT, but it also maintains LH, FSH, and sperm production. However, more research is needed to analyze enclomiphene’s long-term effects.

Can enclomiphene improve fertility?

Research suggests enclomiphene may boost sperm counts and improve fertility outcomes, making it an appealing option for men with low T who want to preserve reproductive potential.

What are the side effects of enclomiphene?

Possible side effects of enclomiphene include headaches, nausea, dizziness, blurred vision, hot flashes, and muscle spasms. It may also increase red blood cell count.

Is enclomiphene FDA-approved?

No. Enclomiphene is not FDA-approved. However, it’s an isomer of clomiphene (Clomid), which is FDA-approved for female infertility. Enclomiphene is available via compounding pharmacies with a prescription.

Who shouldn’t take enclomiphene?

Enclomiphene isn’t suitable for men with primary hypogonadism, men with normal testosterone levels, athletes seeking performance enhancement, or those at risk of blood clots.