Enclomiphene side effects and risks: what the evidence shows

Enclomiphene citrate is one of the two isomers that make up clomiphene, a fertility drug for women that is also prescribed off-label to men with low testosterone. It raises testosterone by making the brain release more luteinizing hormone (LH) and follicle-stimulating hormone (FSH), so the testes produce more of their own. The question this article answers is what that costs in side effects and risks.

The evidence base is thin, and that shapes every answer below. The trials that exist were run by a drug company for a marketing application. In December 2015 the company announced that the FDA had issued a complete response rather than an approval, and the European Medicines Agency (EMA) recommended refusal in January 2018.^[1] Since then, most data come from small studies and retrospective clinic records. Everything here is general information about men treated for low testosterone; it does not replace an assessment by a licensed clinician.

Are there downsides to enclomiphene?

Yes: the main downsides of enclomiphene are its side effects, the gaps in its safety data and the fact that no approved product exists. The FDA summarized the EMA's 2018 assessment in a slide deck for its Pharmacy Compounding Advisory Committee in June 2022. Headache, hot flushes, nausea and muscle spasms led the list of adverse events. Events that led men to stop treatment were blurred vision, muscle spasm, headache and aggression.^[1]

The regulatory status is a downside of its own. In the US, enclomiphene is not an FDA-approved drug, so pharmacies that supply it compound it. A compounded drug has not gone through the FDA's review of safety, effectiveness and manufacturing quality for that product. At the June 2022 meeting, the FDA proposed not adding enclomiphene citrate to the list of bulk substances that pharmacies may use for compounding.^[2] Cost is the third downside. With no approved product, insurance rarely pays. A HealthRX cost report updated on 26 May 2026 puts the out-of-pocket price at US compounding pharmacies at 30 to 120 dollars a month. Dose, pharmacy and any telehealth subscription decide where in that range a man lands.^[3] HealthRX sells treatments in this market, so read the range as an estimate. The comparison of enclomiphene and clomiphene^[4] explains the chemistry and the approval history in more detail.

How risky is enclomiphene?

How risky enclomiphene is cannot be stated precisely, because no long-term controlled trial has measured it. The largest data set is an open-label phase 3 safety study, listed on ClinicalTrials.gov as NCT01534208. It gave 12.5 mg to 216 men and 12.5 mg increasing to 25 mg to 283 men, for 26 weeks.^[1]

The serious events listed in the same study were mostly single cases, among them bradycardia, chest pain, a transient ischemic attack, deep vein thrombosis, pulmonary embolism and atrial flutter.^[1] The study had no placebo group, so these counts cannot show whether enclomiphene caused any of them. The EMA reported that cardiac and thromboembolic events were slightly more frequent with enclomiphene than in men treated with testosterone.

The FDA drew its own conclusion from all sources. Its slides name cardiac and thromboembolic events, elevated estradiol, increased PSA (prostate-specific antigen) and increased hematocrit as the safety concerns. They also note limited data on dose adjustment for people with kidney or liver problems.^[1] In plain terms: the known side effects are mostly mild, but the rare serious ones have not been studied in enough men to rule them out.

Will enclomiphene give you gyno?

Enclomiphene is unlikely to cause gynecomastia, the enlargement of breast tissue in men, judging by the small amount of data available. In a 2024 retrospective study at Baylor College of Medicine, 66 men took clomiphene first and enclomiphene later. Gynecomastia was recorded in 2 men (3 percent) on clomiphene and in none on enclomiphene. Estradiol, a form of estrogen, rose by a median of 17.5 pg/mL on clomiphene and fell by 5.92 pg/mL on enclomiphene.^[5]

That fits with how the two isomers differ. Clomiphene also contains zuclomiphene, and in 15 men on long-term clomiphene, blood levels of zuclomiphene were about 20 times those of enclomiphene.^[6] Enclomiphene alone leaves that isomer out. The Baylor study is small, retrospective and from a single center, and two of its authors report consulting work for drug companies. It also only counted side effects that were coded in the medical notes. The FDA still lists elevated estradiol among enclomiphene's safety concerns,^[1] so breast tenderness or swelling is worth reporting to the prescribing clinician.

Can enclomiphene cause permanent damage?

No study has shown permanent damage from enclomiphene, but no study has followed men long enough to rule it out. The best reassurance concerns hormones. In a trial of 12 men, testosterone fell back to pretreatment values one month after enclomiphene was stopped, while sperm counts had risen during treatment.^[7] That suggests its effect on the hormone axis wears off rather than lasting.

The eyes are the open question. Cataracts appeared in animal studies, so eye examinations were part of the phase 2 and 3 trials. The EMA concluded that the data gave no conclusive evidence that enclomiphene causes new or worsening cataracts. It still recommended ocular safety monitoring in a risk management plan.^[1] For clomiphene, the parent drug, the FDA label is more direct. It warns that visual disturbances are usually reversible, but that prolonged cases have been reported and they may be irreversible, especially at higher doses or with longer use.^[8] Any new blurring, spots or flashes are a reason to call the clinician.

What's the downside of taking testosterone shots?

The main downside of testosterone shots is that they suppress the body's own testosterone and sperm production, and they bring their own risks. The Endocrine Society recommends against testosterone therapy in men planning fertility in the near term.^[9] The American Urological Association (AUA) guideline gives clinicians separate advice for men who want to preserve fertility, for men with cardiovascular disease and for men with prostate cancer.^[10]

Heart safety has the best data. The TRAVERSE trial gave testosterone gel or placebo to 5,246 men aged 45 to 80 with heart disease or a high risk of it. Major cardiac events occurred in 7.0 percent on testosterone and 7.3 percent on placebo. Atrial fibrillation, acute kidney injury and pulmonary embolism were more frequent with testosterone.^[11] The trial used a gel, not injections, and AbbVie, a testosterone maker, funded it.

The comparison is uneven by design: testosterone has much larger trials behind it. Which route fits depends mostly on fertility plans, and the guide to TRT vs enclomiphene^[12] works through that choice.

What are the downsides of taking enclomiphene?

The downsides of taking enclomiphene, as men experience them, are mostly mild symptoms plus the effort of monitoring. In the Baylor records, side effects were noted in 8 of 58 men on enclomiphene (13.8 percent), compared with 31 of 66 on clomiphene (47 percent).^[5]

These figures come from men who switched from clomiphene to enclomiphene, so men who tolerated treatment are overrepresented. They also show that a drug meant to treat low-testosterone symptoms such as low libido can still come with them. Monitoring is part of the treatment. Because the FDA names hematocrit, PSA and estradiol as concerns, expect a clinician to check them in follow-up blood tests. The Elenra guide to the testosterone blood test^[13] explains timing and cost.

What to avoid while taking enclomiphene?

While taking enclomiphene, avoid three things: unsupervised use, unreported new medicines and ignoring changes in your vision. Each one follows from the evidence above.

• Unsupervised or unregulated supply. Enclomiphene is a prescription medicine, prescribed by a licensed clinician after a diagnosis. Products sold online without a prescription have no quality review at all.
• New medicines without a pharmacist check. The body breaks enclomiphene down mainly through the liver enzyme CYP2D6. The EMA asked for more data on dosing in men whose CYP2D6 works poorly and in men with kidney or liver impairment.^[1] Ask a pharmacist whether any medicine you take affects that enzyme.
• Driving with new visual symptoms. Clomiphene's label warns that visual symptoms can make driving or operating machinery more hazardous, especially in changing light.^[8] Report blurring or flashes on enclomiphene before you drive again.

Before treatment starts, the guideline path applies. The American Urological Association names a total testosterone level below 300 ng/dL, measured on two separate mornings and combined with symptoms or signs, as the threshold that supports a diagnosis.^[14] The Endocrine Society asks for a low result to be confirmed with a repeat morning measurement and for LH and FSH to be measured, to tell testicular from pituitary causes.^[9] Take this list of side effects and questions to your clinician or pharmacist. They can weigh it against your own health history, which a general article cannot do.

Frequently asked questions

What are the most common side effects of enclomiphene?

Trial data summarized by the FDA put headache first, followed by hot flushes, nausea and muscle spasms. Most were mild, and the trials were short.

Is enclomiphene safer than clomiphene?

In one retrospective study of 66 men, side effects were recorded less often on enclomiphene than on clomiphene. No randomized trial has compared the two for safety.

Does enclomiphene affect fertility?

In small trials, sperm counts rose or were preserved on enclomiphene, unlike on testosterone. A licensed clinician should confirm whether that applies to your situation.

Sources

1. fda.gov
2. fda.gov
3. healthrx.com
4. elenra.com
5. pubmed.ncbi.nlm.nih.gov
6. pubmed.ncbi.nlm.nih.gov
7. pubmed.ncbi.nlm.nih.gov
8. dailymed.nlm.nih.gov
9. endocrine.org
10. pubmed.ncbi.nlm.nih.gov
11. pubmed.ncbi.nlm.nih.gov
12. elenra.com
13. elenra.com
14. auanet.org