Is Enclomiphene Safe? Side Effects and Risks of Enclomiphene

If you’re looking for a way to boost low testosterone levels without hijacking your fertility (a notorious symptom of testosterone replacement therapy, or TRT), you may have come across a medication called enclomiphene citrate.

Unlike TRT, which introduces synthetic testosterone into the body, drugs like clomiphene and enclomiphene stimulate your body’s hormone production. If you have clinically low testosterone levels, this may help support your energy levels, sex drive, and mood, making it an appealing option if you’re seeking hormonal support without compromising your reproductive health.

But like any drug that affects your hormone levels, enclomiphene isn’t totally risk-free. Below, we’ll answer some of the top questions around this medication, including:

• Is enclomiphene safe?

• What are the side effects of enclomiphene?

• How does enclomiphene stack up against TRT?

First, let’s start with what enclomiphene is and how it works.

Enclomiphene is a selective estrogen receptor modulator (SERM) and one of two isomers in Clomid^® (clomiphene citrate), an FDA-approved fertility drug for women that is also sometimes used in men with secondary hypogonadism (a type of low testosterone caused by faulty signaling between the brain and the testes). While Clomid is more widely known, enclomiphene is gaining attention for its targeted effects and potentially fewer side effects.

Unlike Clomid, enclomiphene is not FDA-approved. Any use is considered off-label, and the medication is only available as a compounded drug product. The FDA does not approve or verify compounded drugs for safety, effectiveness, or quality.

Hims offers access to enclomiphene citrate if you’re approved for treatment after a medical consultation. There are two formulations: enclomiphene as a monotherapy and enclomiphene + tadalafil (Cialis^®) to help increase testosterone levels while improving symptoms of erectile dysfunction, a common symptom of low testosterone.

Enclomiphene has a mechanism of action similar to Clomid. It increases testosterone levels by blocking estrogen signals in the brain, prompting the hypothalamus to release gonadotropin-releasing hormone (GnRH). This stimulates the pituitary gland to secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The release of LH and FSH signals the testes to produce more testosterone and sperm.

One significant difference between enclomiphene and Clomid is that Clomid contains two active ingredients: enclomiphene, which blocks estrogen, and zuclomiphene, which increases estrogen and has a longer half-life (it stays active in the body longer).

Enclomiphene’s long-term safety and effectiveness have not been well established in men. More rigorous, large-scale clinical trials are needed before the medication can be considered a fully validated treatment option.

With that said, one narrative review from 2016 describes enclomiphene as well-tolerated with few adverse effects, but it was mostly studied in women.

Phase II and III clinical trials have reported side effects such as elevated estradiol levels (a form of estrogen), headaches, and abdominal discomfort, with no known long-term complications. Other studies have found that side effects appear less extensive than those linked to clomiphene or traditional testosterone replacement therapy. 

Not only has enclomiphene been shown to raise testosterone levels safely, but it may also help maintain sperm count, making it a compelling option for men concerned about male infertility.

Keep reading for a closer look at the potential side effects.

The research done so far indicates that enclomiphene may have fewer side effects than Clomid and doesn’t adversely affect fertility. However, it does carry its own risks.

Potential side effects of enclomiphene may include:

• Nausea

• Headaches

• Hot flashes

• Aggression

• Muscle spasms

• Blurred vision

• Increase in estradiol, a form of estrogen

Rarely, more serious side effects can occur.

Trials also showed that the use of enclomiphene was linked to a higher risk of venous thromboembolic events (blood clots), cardiac disorders, increased red blood cells and prostate-specific antigen (PSA), eye disorders, and psychiatric disorders compared to placebo users.

Due to the slight risk of blood clots and cardiac disorders, enclomiphene may not be suitable for those with a pre-existing risk of blood clots or those taking blood thinners. Enclomiphene may also not be the right choice for those with a history of heart disease.

Enclomiphene may also not be useful for men with primary hypogonadism, a form of low testosterone that stems from testicular dysfunction.

That said, there are still gaps in our knowledge about enclomiphene, a drug that has not received FDA approval, so work closely with a healthcare provider if you’re considering this medication.

Studies show that SERMs like enclomiphene and clomiphene are metabolized by the liver with the help of the enzyme CYP2D6. If this enzyme is inhibited, it’s possible that the SERMs won’t be sufficiently broken down, but more data is needed.

Rare cases of liver injury in clomiphene users have occurred, but these cases are usually mild and reversible. Drug‑safety summaries on clomiphene have also revealed a risk of elevated hepatic enzymes and hepatitis, though such risks have typically been associated with ovarian hyperstimulation syndrome, which doesn’t apply to male users.

When it comes to enclomiphene, more research is needed to fully understand its risks for the liver.

Enclomiphene is meant to be taken long term, as discontinuing the medication returns testosterone levels to pre-treatment baseline within a month of taking the last dose.

A longitudinal study comparing enclomiphene to clomiphene over two years shows that enclomiphene improved testosterone levels with a lower rate of side effects typically associated with clomiphene, such as mood swings and gynecomastia (breast enlargement). 

However, the authors note that the study doesn’t fully capture enclomiphene’s other potential long-term effects on bone health, body composition, and sexual function.

No, enclomiphene isn’t FDA-approved, but it is an active ingredient in clomiphene, which is an FDA-approved fertility medication for women. 

Using enclomiphene or clomiphene for male hypogonadism is an off-label use. Enclomiphene is also investigational and may be obtained through compounding pharmacies with a prescription or by joining a clinical trial. The FDA does not approve or verify compounded drugs for safety, effectiveness, or quality.

Testosterone replacement therapy is often considered the go-to treatment for clinically diagnosed low testosterone, but it comes with a catch, especially for anyone hoping to have kids. Unlike drugs like clomiphene and enclomiphene, which encourage your body to produce more of its own testosterone, TRT suppresses natural testosterone production, which can have an impact on fertility.

In a study comparing enclomiphene to topical TRT in men with secondary hypogonadism — a condition where the testes produce insufficient testosterone because of a problem in the brain — both treatments boosted testosterone levels, but only enclomiphene did so without compromising sperm production. Meanwhile, more than half of the participants on TRT alone became oligospermic (low sperm count) during treatment, as compared with about 15 percent of men in the enclomiphene citrate group.

Other TRT side effects can include:

• Testicular shrinkage

• Acne

• Skin reactions to topical treatments and injections

• Allergic reactions

• Breast tissue growth

• Hair loss

• Male factor infertility

Other risks of TRT include:

• Enlarged prostate

• Cardiovascular risks

• Obstructive sleep apnea

• Blood clots

When used as prescribed, enclomiphene may be an effective treatment for men with low testosterone. However, there are side effects and risks you should know about.

Here’s what we know:

• Enclomiphene increases testosterone without compromising fertility. Unlike traditional TRT, which can suppress sperm production and reduce fertility, enclomiphene stimulates the body’s natural testosterone production by increasing LH and FSH levels. Studies show that enclomiphene raises testosterone without reducing sperm count.

• Enclomiphene isn’t risk-free. Reported side effects include nausea, headaches, and abdominal discomfort. Rare but more serious risks, like blood clots or cardiac issues, exist, especially in those with pre-existing conditions. We also need more research to fully understand enclomiphene’s long-term safety.

• Enclomiphene isn’t FDA-approved. Enclomiphene isn’t FDA-approved on its own, but it’s a key ingredient in clomiphene, an FDA-approved fertility drug. Doctors can prescribe enclomiphene off-label, typically through compounding pharmacies.

Enclomiphene can be a game-changer in improving hormonal health, but it’s not the only option. There are many ways to help optimize your testosterone production, including following a healthy diet, staying active, getting enough sleep, and more. Learn more in our guide to increasing testosterone naturally.

Hims offers access to enclomiphene and other testosterone treatments for men with low testosterone. If you think you might be a good candidate, schedule a consultation with a healthcare provider to order an at-home testosterone test and explore your options.