Enclomiphene Side Effects in Men: What Trials and Regulators Reported

Enclomiphene side effects are best described from the trial data, because the drug has no FDA-approved label. The most detailed public summary comes from the European Medicines Agency's review of the clinical trials, quoted in the FDA's 2022 briefing document. This guide lists what was reported, how often serious problems showed up, and how enclomiphene compares with Clomid.

The most common side effects

According to the EMA review, the most frequent side effects in the enclomiphene trials were:

• Headache
• Hot flushes
• Nausea
• Muscle spasms

The side effects that most often made men stop treatment were blurred vision, muscle spasm, headache and aggression.

Rare but serious risks regulators flagged

The EMA noted that some events known from testosterone therapy also appeared in the enclomiphene trials, more often than in the placebo group:

• Blood clots: four thromboembolic events were reported, one of them fatal. No such events were reported in men on testosterone or placebo in those trials.
• Heart events: cardiac events were slightly more common than in men on testosterone (0.9% vs 0.7%).
• Lab changes: higher hematocrit (red blood cell share) and PSA.
• Eye and psychiatric events were also reported more often than with placebo.

The EMA said it was unclear whether the clots were caused by higher testosterone, higher estradiol, obesity in the study population, or the drug class. It refused to authorize the product in 2018, concluding safety had not been sufficiently demonstrated.

What about the eyes?

Cataracts showed up in animal studies, so the human trials included eye exams. The EMA found no conclusive evidence that enclomiphene causes or worsens cataracts in men, but recommended continued eye safety monitoring. The FDA briefing also notes that the clomiphene (Clomid) label lists retinal thrombosis among post-marketing reports. Report any vision change to your clinician quickly.

Enclomiphene vs Clomid side effects

Clomid contains enclomiphene plus a second isomer, zuclomiphene. In a 2024 Baylor study of 66 men who took clomiphene and later enclomiphene, decreased libido, low energy and mood changes were all reported significantly less often on enclomiphene, and the odds of any side effect were about 82% lower (odds ratio 0.18). Estradiol also fell slightly on enclomiphene instead of rising. It was a retrospective study, so it shows an association, not proof.

For a full comparison, see our guide to enclomiphene vs Clomid.

Searches people make: hair loss, gyno and stopping

Hair loss is not listed among the most common effects in the trial summaries we reviewed. Breast tenderness or enlargement (gynecomastia) is usually linked to high estradiol, which is one reason clinicians track it.

After stopping, the main change is that testosterone drops back. In a small 2013 trial, levels returned to pre-treatment values within one month. If symptoms of low testosterone come back, that is expected rather than a new side effect.

Labs that help catch problems early

• Total testosterone: confirms the drug is working and not overshooting.
• Estradiol: high levels can cause breast tenderness, mood changes or water retention.
• Hematocrit: a high value thickens the blood, which matters given the clot signal.
• PSA: prostate marker that rose in some trial participants.

Most online programs require labs before prescribing. Our provider comparison shows which ones include follow-up labs and which charge extra. Tell your clinician about any history of blood clots, heart disease, eye disease or mood disorders before you start.

Is enclomiphene safe?

The honest answer is that it is promising but not fully proven. Trials show it raises testosterone without lowering sperm counts, and men report fewer side effects than on Clomid. Regulators in Europe and the United States have not approved it, mainly because of the clot signal and limited long-term data. That is why lab monitoring and a prescriber who follows up matter more than the monthly price.

If you are comparing programs, our T-TIME review explains how one low-cost provider handles labs and follow-up.

How this compares with TRT side effects

Testosterone therapy has its own list. Outside testosterone lowers sperm production, and the large TRAVERSE trial of 5,246 men saw more atrial fibrillation, acute kidney injury and pulmonary embolism on testosterone than on placebo, although major heart events were similar (7.0% vs 7.3%). Enclomiphene keeps sperm production going, but its trials were short and small, so rare long-term risks are less well known. Our enclomiphene vs TRT guide compares the two in more detail.

Whichever you choose, the pattern is the same: confirm low testosterone first, start with a clinician who orders follow-up labs, and report new symptoms early rather than waiting for the next scheduled check.

FAQ

What are the most common side effects of enclomiphene?

Headache, hot flushes, nausea and muscle spasms were the most frequent in the trials reviewed by the EMA. Blurred vision, muscle spasm, headache and aggression were the most common reasons men stopped.

Can enclomiphene cause blood clots?

Four clot events, one fatal, were reported in the trials, and none in the testosterone or placebo groups. The cause was not established, but it is the main safety concern regulators raised.

Does enclomiphene cause hair loss?

Hair loss was not among the most common effects in the trial summaries we reviewed. Any drug that raises testosterone can affect hair in men prone to pattern hair loss, so mention it if it is a concern.

Does enclomiphene have fewer side effects than Clomid?

In one 66-man study, the odds of a side effect were about 82% lower on enclomiphene, with less loss of libido, energy and mood. Larger trials are still needed.

Common misconception: no FDA approval means no regulation at all?

Not quite. Compounding pharmacies are regulated and need a prescription, but compounded drugs are not FDA-approved, so FDA has not reviewed this specific product for safety and effectiveness.

What should I do if I notice vision changes?

Stop and contact your prescriber promptly. Blurred vision was a leading reason for stopping in the trials, and eye safety is still being monitored.