Enclomiphene vs Clomiphene: What a 2024 Study Found

Medically reviewed by Lauren Orta, FNP-C

When men switched from clomiphene to enclomiphene, they reported far fewer side effects and their estradiol stopped climbing. Testosterone held up at least as well.

TL;DR

• Baylor researchers tracked 66 men with low T who took clomiphene, then switched to enclomiphene.
• Odds of a side effect were about 82% lower on enclomiphene (OR 0.18).
• Estradiol rose 17.5 pg/mL on clomiphene but dipped 5.9 pg/mL on enclomiphene.
• Testosterone rose a median 166 ng/dL on enclomiphene vs 98 on clomiphene, but that difference was not statistically significant.

What the study did

Clomiphene (Clomid) is a mix of two mirror-image molecules. Enclomiphene is just one of them, the one that does the work of telling your brain to send more LH and FSH to the testes. The other half lingers in the body longer and is suspected of causing many of clomiphene's mood and estrogen side effects.

This 2024 study in Translational Andrology and Urology (PubMed 39434750; full text on PMC; DOI 10.21037/tau-24-238) looked back at 66 men at Baylor College of Medicine who took clomiphene first, then switched to enclomiphene. Each man had two testosterone readings under 300 ng/dL with symptoms. Average age was about 38, average BMI about 30, and 78% had secondary hypogonadism. Researchers compared labs and documented side effects on each drug, using clomiphene values as the new baseline for enclomiphene.

What it found

• Fewer side effects: lower odds of any adverse event on enclomiphene (odds ratio 0.18; 95% CI 0.07 to 0.44). Decreased libido, low energy and mood changes were each significantly less frequent.
• Estrogen stayed in check: estradiol change was −5.92 pg/mL on enclomiphene vs +17.50 pg/mL on clomiphene (P = 0.001).
• Testosterone: median rise of 166 ng/dL on enclomiphene vs 98 ng/dL on clomiphene. The difference was not statistically significant (P = 0.20), so the fair read is "at least comparable," not "better."

What it means for you

For men with low T who want to keep their own production running, and keep fertility on the table, this is the core appeal of enclomiphene. TRT replaces testosterone from outside and suppresses sperm. Enclomiphene pushes your own system to make more. An older randomized phase II trial found enclomiphene raised testosterone, LH and FSH while conserving sperm counts, unlike testosterone gel (Wiehle et al., Fertil Steril 2014).

This study adds a real-world signal: men who'd already tried clomiphene tolerated enclomiphene better. If clomiphene made you moody or flat, that's worth knowing.

Go deeper: enclomiphene vs TRT, understanding enclomiphene, Clomid vs TRT, and TRT and fertility. Whether enclomiphene fits depends on your type of low T, covered in primary vs secondary hypogonadism.

The fine print

• Retrospective chart review, not a randomized trial. Every man took clomiphene first, so order effects and time can't be ruled out.
• Small: 66 men at one academic clinic.
• Side effects were what got documented in charts, not tracked with standard questionnaires.
• It didn't measure sperm counts.
• Enclomiphene is not FDA-approved. It's prescribed off-label and made by a compounding pharmacy.
• Two authors disclosed consulting ties to testosterone and men's-health companies.

FAQ

Is enclomiphene better than clomiphene?

In this 2024 study of 66 men who switched, enclomiphene had far fewer documented side effects and no estradiol rise. Testosterone gains were comparable. It was a retrospective study, so it is a signal, not proof.

Does enclomiphene raise estrogen?

In this study estradiol fell slightly on enclomiphene (−5.92 pg/mL) while it rose on clomiphene (+17.50 pg/mL).

Does enclomiphene protect fertility?

This study did not measure sperm. An earlier randomized phase II trial found enclomiphene conserved sperm counts while testosterone gel did not.

Is enclomiphene FDA-approved?

No. It is prescribed off-label and prepared by a compounding pharmacy.

Next step

Want to raise T and keep your own production running? Talk it through with a provider. See AZTRT enclomiphene, or book a free consult. AZTRT serves men in Arizona through licensed telehealth providers.

Sources

1. Saffati G et al. Safety and efficacy of enclomiphene and clomiphene for hypogonadal men. Transl Androl Urol. 2024;13(9):1984-1990. PubMed · DOI
2. Wiehle RD et al. Enclomiphene citrate stimulates testosterone production while preventing oligospermia: a randomized phase II clinical trial comparing topical testosterone. Fertil Steril. 2014. PubMed · DOI

This article is for education, not medical advice. Treatment decisions are made with a licensed provider after an evaluation and labs. Results vary.