Enclomiphene Side Effects: What the Studies Show and What to Ask

A 2016 review says enclomiphene appears to be well tolerated with few adverse effects. The side effects reported in trials include higher estradiol, headache and abdominal discomfort, and a 2024 comparison with clomiphene found fewer side effects on enclomiphene. The studies are small, and the review says the long-term effects of enclomiphene remain unknown, so the sections below cover what to ask before you decide.

What side effects does the research report with enclomiphene?

A 2016 enclomiphene review says the side effects reported in phase II and III trials have included elevated estradiol levels, headache and abdominal discomfort. The same review says adverse effects of enclomiphene have not been directly studied, so this list comes from side effects that came up in trials rather than from a dedicated safety study.

A 2024 study from one academic center followed 66 men who took clomiphene and then switched to enclomiphene. Each man was his own comparison, and there was no washout period between the two drugs.

The study was retrospective, small and at a single center, and it did not exclude men with a history of mental health conditions. Its authors call for a blinded randomized trial to confirm the findings.

Is enclomiphene safer than TRT?

The studies compare specific outcomes with testosterone gel. They do not give an overall safety ranking.

• In a 2016 phase III trial of overweight men with secondary hypogonadism, enclomiphene maintained sperm concentration in the normal range, while the abstract says that with testosterone gel “sperm counts were not maintained.”
• A 2025 meta-analysis of randomized trials found no significant difference in total testosterone between SERM therapy (clomiphene and enclomiphene pooled) and testosterone gel. SERM therapy did significantly raise LH and FSH compared with testosterone gel.
• The 2016 review notes FDA concerns about testosterone therapy and its putative cardiovascular risk, and says the long-term effects of enclomiphene remain unknown.

Which option fits you depends on your health history, your fertility goals and your prescriber’s advice.

What happens when you start enclomiphene?

The trials measured hormone changes over weeks and months. In a 2013 study of 12 men, testosterone rose by 3 months on enclomiphene and gel, and LH and FSH increased only in the enclomiphene group. The 2016 review adds that enclomiphene is rapidly absorbed with a half-life of approximately 10 hours. The studies report hormone timing, not day-by-day symptoms, so ask your prescriber what to watch for in the first weeks.

Is it bad to take enclomiphene every day, and how long can you stay on it?

The phase III trial gave men daily oral doses for 16 weeks. In the 2024 study, the median time on enclomiphene was 8.9 months (interquartile range 5.2 to 13.3 months). The 2016 review says the long-term effects of enclomiphene remain unknown. The research does not set a safe length of use. Your prescriber decides that, and the MedlinePlus testosterone levels test page notes that a testosterone test can be used to monitor you if you are taking hormone therapy.

Is 25 mg of enclomiphene too much?

The 2016 review describes a phase II trial of several doses up to 25 mg. All enclomiphene doses increased LH, and men on 25 mg averaged a testosterone of 604 ng/dL. Bring your dose to your prescriber and ask what it means for you.

Does enclomiphene make you feel good, and can you build muscle on it?

The 2016 review says none of the enclomiphene studies evaluated symptom improvement or quality of life using validated measures. It adds that the impact on hypogonadal symptoms remains unknown. In the 2024 comparison, no man on enclomiphene reported mood changes, against 9.1% on clomiphene.

The trial results in this article are about testosterone, LH, FSH, estradiol and sperm counts. Muscle is not one of the outcomes reported, so ask your prescriber whether muscle is a goal they track.

Does enclomiphene raise estrogen, and what about breast changes?

The 2016 review lists elevated estradiol among the side effects seen in enclomiphene trials. In the 2024 study, the median estradiol change was 17.5 pg/mL on clomiphene and −5.92 pg/mL on enclomiphene (P=0.001). That study listed gynecomastia (breast tissue enlargement) among clomiphene effects, but it could not calculate a comparison for it because of too few cases. If you notice breast changes, tell your prescriber.

What about side effects after stopping?

For stopping, the research gives hormone timing. In the 2013 study, testosterone fell back to pretreatment values one month after treatment ended. The 2016 review notes that testosterone increases persisted for at least 7 days after discontinuing. Clomiphene is different: its zuclomiphene isomer has a half-life of about 30 days, which the review links to persistent side effects. Ask your prescriber what to expect when treatment ends and which labs will be checked.

What are the dangers of taking enclomiphene?

The main documented risks are the side effects listed above, and the long-term picture is unknown. Separately, the FDA warns about a wider problem. Its page on tainted sexual enhancement products says that many products that claim to help with sexual enhancement or treat sexual dysfunction “are likely to be contaminated with dangerous hidden ingredients,” that they “pose a serious health risk,” and that they “can lead to severe health issues and hospitalization.”

Is enclomiphene FDA approved, and where can you get it?

The 2016 review says the FDA began reviewing enclomiphene in 2007 and did not approve it for secondary hypogonadism. A meeting to review the application was canceled in November 2015 over concerns about the bioanalytical method, and the review concludes that “at this point, the future of enclomiphene is uncertain.” This is the 2016 status. For the current status, check the FDA’s drug information or ask your pharmacist. This is information, not legal advice.

When you look for it near you, ask a prescriber and a pharmacy to confirm the product name and the maker on the label. This page does not name sellers.

What are the benefits of enclomiphene in the studies?

The research reports higher testosterone, higher LH and FSH, and maintained sperm counts. The table lists the studies behind those results.

The 2016 review notes that none of the enclomiphene studies measured symptom improvement with validated tools, so the benefit on how you feel is still open.

What should you combine with enclomiphene?

The studies here compare enclomiphene with placebo, testosterone gel or clomiphene. The 2025 meta-analysis pooled a combination: its abstract says SERM therapy and SERM plus hCG both produced higher testosterone than hCG alone. Whether any combination fits you is a decision for your prescriber, who can review every medicine and supplement you take.

What to bring to your prescriber

• What dose you would start on, and how and when it would be adjusted.
• How long treatment is expected to last, and which lab tests will be checked before and during.
• Which side effects to report, such as libido, energy, mood or breast changes, and how quickly to report them.
• Whether any medicines or supplements you take should be reviewed with your pharmacist.
• What the product costs, and the name and maker printed on the label.

MedlinePlus advises not stopping any medicine unless your provider tells you to. To keep a clear record, the medication side effects and adverse events guide shows how to build a timeline, and the Prolia side effects guide shows the kind of question list that works for another prescription.

By the Clear Health Evidence Team

This article is for general information purposes only and does not constitute medical advice. Consult your doctor or qualified healthcare provider before making changes to your health routine.