Is Enclomiphene FDA-Approved?

Key Takeaways: 

• Enclomiphene citrate isn’t FDA-approved, but studies show it can raise testosterone levels and may help preserve sperm counts more effectively than testosterone replacement therapy.

• The medication works by stimulating your body’s own testosterone production, which can make it appealing for men who want to maintain fertility. Other therapies supplement natural levels of the hormone and may be associated with fertility risks. 

• While enclomiphene is generally well-tolerated, long-term safety and effectiveness are unconfirmed because existing studies are small and short-term.

• You can access enclomiphene through certain compounding pharmacies with a prescription after a medical evaluation and hormone testing.
  

Enclomiphene is a non-steroidal selective estrogen receptor modulator (SERM) that helps stimulate your body’s natural testosterone production. While it’s not FDA-approved, it’s one of the two isomers found in clomiphene citrate — a medication that is FDA-approved to treat female infertility. Clomiphene citrate is also sometimes prescribed off-label to men with low testosterone.

Unlike other treatments for low testosterone, like testosterone replacement therapy (TRT), medications like enclomiphene and clomiphene don’t suppress sperm production. In fact, studies show enclomiphene may even improve sperm count in men with secondary hypogonadism, a type of low testosterone caused by faulty signaling between the brain and the testes.

So why doesn’t the Food and Drug Administration (FDA) approve enclomiphene? It’s impossible to say for sure, but a key reason is regulatory: The FDA determined that the clinical trial data for the medication were not sufficient to prove a clear benefit. Enclomiphene remains investigational in the U.S., and research and regulatory oversight continue.

Keep reading if you’re curious about how enclomiphene is regulated and what the latest science specifies about its benefits and risks.

Here are five fast facts about enclomiphene:

• Enclomiphene is not approved by the FDA. Despite this truth, the drug is one of the active ingredients in clomiphene citrate (sold under the brand name Clomid^®), an FDA-approved fertility medication for women that’s sometimes used off-label to treat low T in men.

• Enclomiphene’s efficacy for treating low testosterone is still the subject of research. While some healthcare providers may prescribe it through compounding pharmacies, enclomiphene is not widely accessible. The ability to fill a prescription for it may depend on local pharmacy practices and state rules.

• You need a prescription to take enclomiphene. Enclomiphene isn’t a dietary supplement. You can only acquire it with a prescription, typically through select compounding pharmacies, though not all compounding pharmacies may fill the prescription.

• Enclomiphene is generally safe and well-tolerated. Clinical trials and reviews describe enclomiphene as leading to mostly mild side effects, such as headache or hot flashes. Still, long-term safety data are limited, and larger clinical trials are needed.

• Enclomiphene may preserve fertility while increasing testosterone. Unlike TRT, which can reduce sperm production, enclomiphene helps stimulate the body’s testosterone production and may even improve sperm counts in some men with secondary male hypogonadism.

Small randomized and controlled studies show that oral enclomiphene can raise testosterone and tends to preserve or improve sperm counts in weeks or months. However, the evidence is limited to relatively small and short trials, and larger, longer trials are needed to confirm the benefits and long-term safety.

Like clomiphene, enclomiphene raises testosterone by stimulating the body’s own hormone production. However, clomiphene contains zuclomiphene, the cis-isomer with a longer half-life and partial estrogen-agonist activity. Research links zuclomiphene to side effects such as mood changes, male breast growth (gynecomastia), and elevations in estradiol (a potent form of estrogen). By isolating enclomiphene — the trans-isomer with primarily anti-estrogenic activity — researchers aimed to achieve the testosterone-boosting benefits that clomiphene offers, but with fewer estrogen-related effects.

Enclomiphene itself is an estrogen receptor antagonist. It helps your body make more testosterone by interfering with estrogen’s negative feedback on the hypothalamic-pituitary-gonadal axis, in turn prompting the release of gonadotropins.

Enclomiphene works by binding to estrogen receptors in the brain, which signals the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Increased LH and FSH levels lead the testes to produce more sperm and testosterone.

Enclomiphene is not FDA-approved.

Originally developed under the brand name Androxal^® by Repros Therapeutics Inc.^®, enclomiphene’s request for FDA approval was rejected in a Complete Response Letter (CRL) in 2015. The FDA advisory committee determined that the studies Repros submitted were not designed well enough to demonstrate a clear clinical benefit of taking enclomiphene. Importantly, a CRL does not necessarily mean a drug is unsafe; it indicates that the FDA requires more robust evidence before granting approval. 

In enclomiphene’s case, the FDA recommended that Repros Therapeutics complete additional Phase 3 trials to address its concerns. However, those studies were never completed, possibly due to corporate shifts after Allergan acquired Repros in 2017.

Enclomiphene remains unapproved and is not included on the 503A Bulks List, which defines the bulk substances permitted for compounding under Section 503A of the Federal Food, Drug, and Cosmetic Act. This omission followed a 2022 Pharmacy Compounding Advisory Committee (PCAC) vote, which makes routine compounding nationwide more tricky. However, though enclomiphene is not on the 503A bulks list, certain pharmacies can compound it because it is a component of an FDA-approved drug, clomiphene. 

We don’t know much about the long-term safety of enclomiphene, but the medication is generally well-tolerated with few adverse effects.

Side effects of enclomiphene recorded in trials include:

• Headaches

• Dizziness

• Nausea

• Hot flashes

• Blurred vision

• Muscle spasms

Adverse events in published trials were generally uncommon and mostly mild, but trials were also notably small and not powered to detect rare serious events. For this reason, the long-term safety of taking enclomiphene remains unestablished.

Far less common but more serious side effects have also been reported, including an increased risk of blood clots, elevated red blood cell counts, cardiac issues, eye problems, psychiatric disorders, and elevated prostate-specific antigen (PSA) levels.

Multiple studies have shown enclomiphene to be effective in increasing blood testosterone levels in hypogonadal men and preserving sperm counts better than exogenous testosterone (TRT).

In a small placebo-controlled study that compared enclomiphene to testosterone gel, enclomiphene increased free and total testosterone in a dose-dependent manner over the course of 14 days.

At the start of the study, participants had low-to-borderline-low testosterone, averaging 275 nanograms per deciliter (ng/dL). After two weeks, men taking enclomiphene saw clear, dose-dependent improvements and a restoration of normal testosterone levels:

• On average, a 12.5-mg dose increased testosterone to 412 ng/dL

• On average, a 25-mg dose increased testosterone to 520 ng/dL

• On average, a 50-mg dose increased testosterone to 589 ng/dL

Testosterone gel, on the other hand, raised levels to 473 ng/dL, similar to the mid-dose of enclomiphene. However, unlike testosterone gel — which disproportionately boosted dihydrotestosterone (DHT), an androgen linked to side effects like hair loss and prostate enlargement — enclomiphene maintained a more balanced testosterone-to-DHT ratio. 

Data on clinical outcomes, including improvements in symptoms of low testosterone (libido, mood, energy), long-term safety, cardiovascular risk, or prostate health, remain limited. (The aforementioned study had few participants.) Larger, longer-duration studies are needed to confirm both efficacy and safety in broader populations.

There is not enough data to know for sure how enclomphene impacts symptoms of low T.

Research does support a link between testosterone deficiency and a number of symptoms, including low libido, erectile dysfunction (ED), mood changes, fatigue, depression, reduced muscle mass and strength, increased body fat, and even decreased body hair.

Furthermore, clomiphene citrate, which contains enclomiphene, is proven to improve both clinical symptoms and biochemical markers of male hypogonadism.

It’s also true that enclomiphene and clomiphene provide the same magnitude of improvement in testosterone levels in a head-to-head comparison. However, enclomiphene has a lower rate of documented adverse events.

Taken together, the evidence suggests that enclomiphene may offer the benefits of clomiphene but with fewer side effects. This makes enclomiphene an appealing option for men seeking to restore testosterone.

Still, while early findings are encouraging, the research is limited. Larger, longer-term studies are needed to confirm not just enclomiphene’s effect on hormone levels, but also whether it consistently improves the day-to-day symptoms that matter most, including energy, sexual function, mood, and overall quality of life.

You can only access enclomiphene through compounding pharmacies, and you’ll also need a valid prescription from a licensed healthcare provider. 

Hims offers access to enclomiphene and other testosterone treatments following a consultation with a healthcare provider and at-home blood testing. In addition to enclomiphene as a monotherapy, Hims also offers access to a 2-in-1 treatment containing enclomiphene and tadalafil (Cialis^®) to target low T and ED at once. 

Before you start treatment, you’ll need to undergo a thorough medical evaluation, which typically assesses testosterone levels, LH/FSH biomarkers, and overall health. 

Once you begin treatment, regular follow-up is key. Your provider will track your progress, adjust your dosage if necessary, and make sure your testosterone levels (and overall health) are moving in the right direction.

Whether or not you’re taking enclomiphene, you can also support your testosterone production naturally through lifestyle tweaks like following a healthier diet, lowering your stress levels, making time for exercise, and more.

Enclomiphene is emerging as a promising treatment option for men with low testosterone who don’t want to compromise their fertility while giving their T levels a boost. While the FDA does not approve the medication, enclomiphene is a potential alternative to testosterone replacement therapy (TRT) for certain people.

Here’s what we know:

• Enclomiphene isn’t FDA-approved — yet. The FDA rejected its application due to study-design issues. It remains investigational in the U.S. but can be accessed through certain compounding pharmacies with a valid prescription.

• Enclomiphene has promising benefits for testosterone and fertility. Unlike TRT, which suppresses sperm production, enclomiphene raises testosterone levels while preserving sperm count. This makes it especially appealing for men with low T who want to maintain fertility.

• Enclomiphene is generally safe, but more research is needed. Studies suggest enclomiphene is generally well-tolerated and effective at boosting testosterone, with fewer side effects than clomiphene and TRT. However, data on long-term safety and effectiveness remain limited.

Want to learn more about hormonal health? Check out our complete guide to testosterone. 

Is enclomiphene FDA-approved?

No. Enclomiphene isn’t FDA-approved, though it is one of the ingredients in clomiphene citrate, which is an FDA-approved fertility drug. 

How does enclomiphene work?

Enclomiphene blocks estrogen, stimulating the brain to release hormones that tell the testes to produce more testosterone and sperm. This is different from traditional testosterone replacement therapy (TRT), which supplies the hormone directly. 

How is enclomiphene different from testosterone replacement therapy?

Unlike TRT, enclomiphene doesn’t suppress sperm production and may even help preserve or improve fertility.

Is enclomiphene effective for low testosterone?

Research shows enclomiphene can raise testosterone levels and maintain sperm counts, but larger studies are needed to confirm long-term benefits.

Why hasn’t the FDA approved enclomiphene?

The FDA found that past clinical trials didn’t clearly prove the medication’s benefits, so more research is needed before approval.

Can doctors still prescribe enclomiphene?

Yes. Some healthcare providers prescribe enclomiphene off-label through compounding pharmacies after a medical evaluation.

Do I need a prescription for enclomiphene?

Yes. Enclomiphene isn’t available as an over-the-counter supplement and requires a prescription.

What’s the difference between enclomiphene and clomiphene?

Clomiphene contains two isomers: enclomiphene and zuclomiphene. Enclomiphene provides the testosterone-boosting effects with fewer estrogen-related side effects.

What are the common side effects of enclomiphene?

Headaches, dizziness, nausea, hot flashes, and blurred vision are the most commonly reported side effects.

This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment. Learn more about our editorial standards here.