Enclomiphene
Enclomiphene raises the body's own testosterone, LH and FSH in men with secondary hypogonadism while keeping sperm counts in the normal range, which testosterone therapy does not. It is not FDA-approved: in the US it comes from clinics and telehealth services through compounding pharmacies. Its trials did not test symptoms such as sex drive, energy or bone strength, so no benefit for them has been shown.
Prescription medication: not a dietary supplement
This is an FDA-approved (or investigational) drug, not a supplement. It requires a prescription and medical supervision. The information below summarizes clinical-trial evidence for education only. It is not a recommendation to obtain or use it without a doctor.
Quick decision guide
May help most
Men with confirmed secondary hypogonadism who want to keep sperm production, treated by a clinician experienced in male hormones, with a prescription
Common dosing range
No approved dose. Trials studied 12.5 mg or 25 mg by mouth once daily; a prescriber sets the dose
When to expect effects
Testosterone rose within about 2 weeks in trials; sperm results were measured at 3 to 6 months
Watch out for
Not approved by FDA or EMA; the EMA recommended refusal in 2018, citing blood clot risk and missing symptom data; compounded products are not FDA-checked for quality
What is it
Enclomiphene (also spelled enclomifene; usually given as enclomiphene citrate) is a selective estrogen receptor modulator (SERM) taken by mouth. It is one of the two isomers that make up clomiphene, an FDA-approved drug; the other is zuclomiphene, and clomiphene is 50 to 70 percent enclomiphene. Enclomiphene itself is not approved by the FDA or by the European Medicines Agency (EMA). In 2015 its developer, Repros Therapeutics, announced that FDA had not approved its application (a complete response), saying the phase 3 trials were not designed to show clinical benefit, and in January 2018 the EMA's medicines committee recommended refusing a marketing application under the name EnCyzix. In the US it is prescribed off-label by clinics and telehealth services and made by compounding pharmacies, which may compound it only for a named patient with a valid prescription. FDA lists it as a compounding ingredient still under evaluation (Category 1). Its advisory committee voted 8 to 4 in June 2022 against adding it to the list of allowed compounding ingredients, but FDA has not issued a final rule. Compounded versions are not FDA-approved, so FDA does not check their safety, effectiveness or quality before they are sold.
Is it worth it for you?
Use this as a quick fit check, not a diagnosis.
Worth considering if…
Probably skip if…
Evidence at a glance
| Goal | Effect | Best fit | Time |
|---|---|---|---|
testosterone levels in secondary hypogonadism Good Evidence | About 274 ng/dL higher than placebo (95% CI 191.87 to 355.66 ng/dL, pooled with clomiphene); similar to testosterone gel | Men with low testosterone and low or normal LH (secondary hypogonadism), including overweight men | Within about 2 weeks |
LH and FSH levels Good Evidence | LH 4.66 IU/L and FSH 4.59 IU/L higher than placebo; opposite in direction to testosterone gel | Men with secondary hypogonadism whose pituitary signals are low or inappropriately normal | Within about 2 weeks |
sperm counts compared with testosterone therapy Limited Evidence | Sperm concentration 70.40 million/mL higher than with testosterone gel; no clear difference from placebo | Men with secondary hypogonadism who want to keep their fertility, or who are coming off testosterone | Measured at 3 to 6 months |
testosterone levels in secondary hypogonadism
- Effect
- About 274 ng/dL higher than placebo (95% CI 191.87 to 355.66 ng/dL, pooled with clomiphene); similar to testosterone gel
- Best fit
- Men with low testosterone and low or normal LH (secondary hypogonadism), including overweight men
- Time
- Within about 2 weeks
LH and FSH levels
- Effect
- LH 4.66 IU/L and FSH 4.59 IU/L higher than placebo; opposite in direction to testosterone gel
- Best fit
- Men with secondary hypogonadism whose pituitary signals are low or inappropriately normal
- Time
- Within about 2 weeks
sperm counts compared with testosterone therapy
- Effect
- Sperm concentration 70.40 million/mL higher than with testosterone gel; no clear difference from placebo
- Best fit
- Men with secondary hypogonadism who want to keep their fertility, or who are coming off testosterone
- Time
- Measured at 3 to 6 months
Evidence for 3 uses
AI-assisted evidence assessment. Talk to your doctor before relying on any single supplement.
testosterone levels in secondary hypogonadism
Biomarker supportIn two phase 3 trials (ZA-304 and ZA-305), overweight men aged 18 to 60 with morning testosterone of 300 ng/dL or less and low or normal LH took enclomiphene, testosterone gel or placebo for 16 weeks. Testosterone rose in all active groups, and enclomiphene restored normal testosterone levels. In a 6-week phase 2 trial (44 men completed it), men on 25 mg daily reached 604 ± 160 ng/dL, compared with 500 ± 278 ng/dL on testosterone gel, a difference that was not significant. A 2025 meta-analysis of 10 randomized trials (819 men, followed 2 to 30 weeks), which pooled enclomiphene with clomiphene, found testosterone about 274 ng/dL higher than placebo (moderate-quality evidence) and no significant difference from testosterone gel. The phase 2 trial was led by researchers at the developer, Repros Therapeutics, and all the trials were short.
Bottom line: It reliably raises testosterone on blood tests; that number alone has not been shown to make men feel better.
LH and FSH levels
Biomarker supportEnclomiphene raises the pituitary hormones LH and FSH, while testosterone gel lowers them. For LH, this opposite effect appeared within the first 2 weeks of a 6-week phase 2 trial and was still present at 16 weeks in the phase 3 trials. In the phase 2 trial, LH and FSH rose above the normal range. In the 2025 meta-analysis, which pooled enclomiphene with clomiphene, LH was 4.66 IU/L and FSH 4.59 IU/L higher than with placebo (moderate-quality evidence), and both were also higher than with testosterone gel.
Bottom line: It works through the body's own hormone signals, which is thought to be why sperm counts were kept in trials.
sperm counts compared with testosterone therapy
Biomarker supportIn the phase 3 trials, sperm concentration stayed in the normal range over 16 weeks on enclomiphene, while testosterone gel caused a marked fall. In a small open-label trial of 12 men who had previously used testosterone gel, enclomiphene raised sperm counts in 7 of 7 men at 3 months and 6 of 6 men at 6 months, while the gel did not raise counts above 20 million/mL in any of the 5 men at 3 months. The 2025 meta-analysis found sperm concentration 70.40 million/mL higher than with testosterone gel, and far fewer men below 15 million/mL (risk ratio 0.10). Sperm count is a lab measure: the trials did not report pregnancies or live births.
Bottom line: Unlike testosterone, it does not shut down sperm production; whether that leads to more pregnancies is unknown.
Evidence is mixed
Compared with placebo, the meta-analysis found no significant difference in sperm concentration (7.50 million/mL, p = 0.59). A retrospective study of 46 men on enclomiphene found no significant change in sperm concentration, though total motile sperm count rose. The clearest effect is avoiding the drop that testosterone causes, not raising counts above normal.
How it works
How to take it
What to track
Bottom line: An unapproved, compounded drug with short-term hormone data; any use needs a prescriber, a clear goal and regular blood tests.
Safety
Know the common side effects, key cautions, and who should avoid it.
Common side effects
Serious risks
Blood clots in the veins (venous thromboembolism), such as deep vein thrombosis and pulmonary embolism. The EMA named this risk as a reason to refuse approval, and FDA's 2022 review listed both among serious events in a safety study.
Heart and circulation events. In FDA's summary of a safety study, serious events included slow heart rate, chest pain, transient ischemic attack (mini-stroke), low blood pressure and atrial flutter, and the EMA review found cardiac and clot events slightly more often than with testosterone. A 2026 case report described atrial flutter in a 46-year-old man with earlier heart valve surgery after he took 50 mg instead of 25 mg daily; the authors could not establish that the drug caused it.
Eye effects. Blurred vision was among the side effects that led people to stop in the EMA review, and cataracts were seen in animal studies. The EMA found no conclusive evidence of cataracts in people but asked for eye safety monitoring. An early trial excluded men with cataracts.
Raised estradiol, PSA and hematocrit (red blood cell level). FDA listed these as safety concerns; in the phase 3 trials one man on 25 mg stopped because of high hematocrit and one because of high PSA.
Unknown long-term safety. Trials lasted weeks to months, and data on dosing in older adults and in people with kidney or liver impairment are incomplete.
Compounded product quality. Compounded drugs are not FDA-approved, so FDA does not verify their safety, effectiveness or quality before they are sold, and poor compounding can produce too much or too little active ingredient.
Who should avoid it
- People with a history of liver disease (liver toxicity was also seen in high-dose animal studies)
- People with uncontrolled adrenal or thyroid problems
- People with certain pituitary conditions
- People allergic to clomiphene or enclomiphene
- People who have had a blood clot or have a high clot risk, unless a specialist has weighed that risk, because clot risk was a reason for the EMA refusal
- Women who are or may become pregnant: it is intended for men, and animal studies showed pregnancy loss
Pregnancy & breastfeeding
Enclomiphene is developed and prescribed for men and has no established use in pregnancy. In animal studies summarized by FDA, it was linked to pregnancy loss (more resorptions and post-implantation loss) and altered sperm.
Choosing a product
What to look for on the label, and what to be skeptical of.
Look for…
Be skeptical of…
Frequently asked questions
Is enclomiphene FDA-approved?⌄
No. No FDA-approved drug contains enclomiphene as its active ingredient, and the European Medicines Agency's medicines committee recommended refusing it in 2018. In 2015 the developer announced that FDA had not approved its application because the phase 3 trials were not designed to show clinical benefit. Clomiphene, which contains enclomiphene as one of its two parts, is an approved drug.
How do people in the US get enclomiphene?⌄
Through a prescription from a clinic or telehealth service, filled by a compounding pharmacy. FDA lists enclomiphene as a compounding ingredient still under evaluation. Its advisory committee voted 8 to 4 in June 2022 against adding it to the list of allowed ingredients, but FDA has not made a final decision. Compounded versions are not FDA-approved, so FDA does not check their safety, effectiveness or quality before they are sold.
Will enclomiphene improve my sex drive or energy?⌄
That has not been shown. The main trials measured testosterone, LH, FSH and sperm counts, and FDA's 2022 review noted that enclomiphene trials did not evaluate symptoms or quality of life. The EMA cited this gap when it refused approval, and FDA guidance says it is unclear whether raising testosterone in this group brings clinical benefit. Talk with your doctor about what is known for your situation.
Does enclomiphene protect fertility?⌄
It keeps sperm counts in the normal range in short trials, while testosterone gel lowers them. But no trial reported pregnancy or live birth rates, and FDA does not consider better semen results alone proof of better fertility.
How is enclomiphene different from clomiphene?⌄
Clomiphene is a mix of two forms of the same molecule (geometric isomers), enclomiphene and zuclomiphene, and is 50 to 70 percent enclomiphene. Zuclomiphene acts more like estrogen, while enclomiphene is the form that raises LH and FSH. A retrospective study of 66 men found fewer reported side effects after they moved from clomiphene to enclomiphene, but a study of that kind cannot prove the difference.
What are the main safety concerns?⌄
Blood clots in the veins, heart rhythm and other cardiac events, eye effects such as blurred vision, and rises in estradiol, PSA and hematocrit, with no long-term safety data. Compounded products add a quality risk. Ask your doctor or pharmacist how these apply to you.
References by claim
testosterone levels in secondary hypogonadism
sperm counts compared with testosterone therapy
Safety
European Medicines Agency: Refusal of the marketing authorisation for EnCyzix (enclomifene), EMA/CHMP/54473/2018 · EMA link
FDA Pharmacy Compounding Advisory Committee, transcript of June 8, 2022 meeting (FDA presentation on enclomiphene citrate) · FDA link
Tariq et al., 2026 · PMC (2026) link
Foster et al., 2026 · PMC (2026) link
FDA: Compounding and the FDA, questions and answers · FDA link
Track Enclomiphene with Pilora
Set up dose reminders, check interactions, and join the community in the Pilora app.
Disclaimer: This page summarizes published clinical-trial data for educational purposes and is not medical advice or a recommendation to use this prescription medication. Dosing, eligibility, and monitoring must be decided by a licensed prescriber.