Short answer: clomiphene (Clomid) is two drugs in one pill, and enclomiphene is the faster, more targeted half of it. Clomiphene is a mix of two isomers, enclomiphene and zuclomiphene. Both products block estrogen feedback in the brain, so LH, FSH and testosterone rise. Enclomiphene alone clears in about 8–10 hours, while zuclomiphene lingers for over a month. Clomiphene is an approved medicine (for women; off-label in men). Enclomiphene reached Phase 3 trials in men but was refused approval in the US and the EU.
Enclomiphene vs clomiphene at a glance
| Enclomiphene | Clomiphene | |
|---|---|---|
| What it is | Selective estrogen receptor modulator (SERM); the trans-isomer of clomiphene | Selective estrogen receptor modulator (SERM); a mixture of two isomers, enclomiphene (trans) and zuclomiphene (cis) |
| Approval | Not approved; furthest stage: Phase 3 (marketing applications filed; not approved) | Approved (FDA 1967) for ovulatory dysfunction in women; off-label in men |
| Human studies (counted in our records) | 7 | 815 |
| Half-life | ~8–10 h | No single value: enclomiphene part ~5–10 h; zuclomiphene part ~24 h with a very long tail (detectable for over a month) |
| Testosterone suppression score | 0/3 | 0/3 |
| Liver risk score | 1/3 | 1/3 |
| Evidence score | 2/3 | 2/3 |
| WADA | Prohibited at all times (in and out of competition) (S4.2 Anti-estrogenic substances) | Prohibited at all times (in and out of competition) (S4.2 Anti-estrogenic substances) |
| Isomers | Trans isomer only | Enclomiphene (trans) + zuclomiphene (cis) |
| Estradiol | Rises less in comparison studies | Rises during treatment |
| SwissChems product | Enclomiphene (12.5mg/capsule), 60 Capsules | Clomiphene, 1500mg (25mg/capsule) |
Scores run from 0 (none) to 3 (high); see our methodology. Data from the SARMs database.
Source: Sarmguide compound database; Enclomiphene value: EnCyzix (enclomifene): public assessment report, EMA/88321/2018 (2018).
How they work
Both are SERMs (selective estrogen receptor modulators). In the hypothalamus and pituitary, estrogen normally tells the body to make less LH and FSH. Blocking that signal makes the pituitary release more LH and FSH, and the testes respond with more testosterone and sperm. This is the opposite of what testosterone itself does: testosterone gel lowered LH and FSH in the same trials. That is why both are discussed for restarting natural production after SARMs or steroids.
The difference is the second isomer. Zuclomiphene has a much longer half-life than enclomiphene and stays detectable for more than a month after single doses; in men on long-term clomiphene, zuclomiphene builds up in the blood. In a mouse study, the two isomers had different effects on reproductive tissues, which is the basis for the idea that enclomiphene alone may be “cleaner”.
What the trials show
| Evidence | Enclomiphene | Clomiphene |
|---|---|---|
| Raises testosterone in hypogonadal men | Yes, in Phase 2 and Phase 3 trials (e.g. +197 to +259 ng/dL in 3 months) | Yes; meta-analysis of 19 studies, 1,642 men |
| Compared with testosterone gel | Similar testosterone; LH, FSH and sperm counts kept, unlike gel | Similar testosterone to gel in 11 studies; lower libido scores than testosterone |
| Sperm | Sperm counts stayed normal in two Phase 3 trials (61–66% met the combined goal vs 16% on gel) | Used off-label for male infertility |
| Symptoms (libido, energy) | Not shown; FDA and EMA said symptom benefit was not demonstrated | Symptom scores improved in the meta-analysis |
| Long-term use | 6-month open-label safety study (490 men) | Studies of up to 3+ years in men |
A 2025 meta-analysis of randomized trials that pooled both drugs found that SERM therapy raised total testosterone by about 274 ng/dL over placebo, with LH and FSH up too, and no significant difference in testosterone compared with testosterone gel.
Head-to-head comparisons
There is no randomized head-to-head trial. Two observational studies compared them directly:
- In 66 men at one US clinic who switched from clomiphene to enclomiphene, the median testosterone rise was similar (166 vs 98 ng/dL, not significantly different), estradiol changed −5.9 vs +17.5 pg/mL, and decreased libido, low energy and mood changes were reported less often on enclomiphene.
- In a retrospective study of 46 men on enclomiphene and 32 on clomiphene for infertility, both raised testosterone, but only enclomiphene significantly raised LH, FSH and total motile sperm count.
Side effects
| Enclomiphene | Clomiphene |
|---|---|
| Headache, hot flushes, nausea, muscle spasm were the most frequent in EMA’s review | Visual symptoms (blurring, spots, flashes) are a label warning; usually reversible but can be prolonged |
| Four blood-clot events in men on enclomiphene in the trials (none on gel or placebo); EMA cited the risk in its refusal | Mood changes and breast tenderness in long-term male users (8% reported side effects over 3+ years) |
| Blurred vision and cataract slightly more common than placebo; eye monitoring requested | Estradiol rises; HDL fell vs placebo in one trial |
| Raised hematocrit and PSA listed as concerns | PSA and hematocrit unchanged in a year-long study of 77 men |
Approval and legal status
Clomiphene (Clomid) was approved by the FDA in 1967 for ovulatory dysfunction in women and is prescription-only; use in men is off-label. Enclomiphene (Androxal, EnCyzix) received an FDA complete response letter in 2015 asking for more Phase 3 work, and the EU refused authorization in 2018. The FDA lists enclomiphene citrate in 503A Category 1 (under evaluation for compounding). In the UK it is unlicensed. Both are banned in sport under WADA S4.2 (anti-estrogenic substances), and WADA’s 2026 technical letter covers clomifene and its isomers.
After SARMs: which is used for PCT?
Neither has been tested in a trial for recovery after SARMs. The rationale for both is the same: raise LH and FSH so the testes restart. Observational data on recovery after anabolic steroids suggest most men recover within months without treatment, and post-cycle therapy has only been linked to faster recovery in observational studies. We do not give PCT protocols; see SARMs PCT, the PCT and bloodwork planner, Clomid PCT and the drug pages for enclomiphene and clomiphene.
Verdict
Both raise LH, FSH and testosterone. Clomiphene has decades of use and approval (for women) but drags along zuclomiphene, which lingers for weeks and is linked to more estrogenic side effects. Enclomiphene is the cleaner molecule with strong hormone data from Phase 3 trials, but it is not approved anywhere, and its trials raised a blood-clot signal and eye-safety questions. The only head-to-head data are observational and favor enclomiphene on side effects. For a comparison with tamoxifen, see Nolvadex vs Clomid.
Frequently asked questions
What is the difference between enclomiphene and clomiphene?
Enclomiphene is half of clomipheneEvidence: Human data
Clomiphene is a mixture of two isomers, enclomiphene and zuclomiphene. Enclomiphene is the trans isomer on its own, with a half-life of about 8–10 hours, while zuclomiphene stays detectable for over a month.
Is enclomiphene better than clomiphene?
Unclear; no head-to-head trialEvidence: Human data
There is no randomized head-to-head trial. In observational studies, enclomiphene raised testosterone similarly, with lower estradiol and fewer reported side effects, and raised LH, FSH and sperm more in one infertility study.
Is enclomiphene FDA approved?
NoEvidence: Law
The FDA issued a complete response letter in 2015 and the EU refused authorization in 2018. The FDA lists it in 503A Category 1 for compounding, under evaluation.
Is clomiphene the same as Clomid?
YesEvidence: Law
Clomid is a brand name for clomiphene citrate, approved by the FDA in 1967 for ovulation problems in women. Use in men is off-label.
Does enclomiphene raise estrogen?
Less than clomipheneEvidence: Human data
In men who switched from clomiphene, estradiol changed −5.9 pg/mL on enclomiphene vs +17.5 pg/mL on clomiphene. These are observational data, not a randomized trial.
Enclomiphene vs Clomid for PCT: which is used?
Neither tested for thisEvidence: Limited
Both are used off-label to restart LH and FSH after SARMs or steroids, but neither has been tested in a trial for that purpose.
What are the side effects of enclomiphene vs clomiphene?
Different risks for eachEvidence: Trial
Enclomiphene: headache, hot flushes, nausea and a blood-clot signal in trials. Clomiphene: visual symptoms (a label warning), mood changes, breast tenderness and higher estradiol.
Are enclomiphene and clomiphene banned in sport?
Yes, banned by WADAEvidence: Law
Both fall under WADA S4.2 (anti-estrogenic substances) and are prohibited at all times.
Sources
- Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: restoration instead of replacement
- Enclomiphene citrate stimulates testosterone production while preventing oligospermia: a randomized phase II clinical trial comparing topical testosterone
- Testosterone Restoration by Enclomiphene Citrate in Men with Secondary Hypogonadism: Pharmacodynamics and Pharmacokinetics
- Clomiphene citrate for men with hypogonadism: a systematic review and meta-analysis
- Clomiphene citrate versus testosterone replacement therapy in male hypogonadism: a systematic review of literature and meta-analysis
- Clomiphene or enclomiphene citrate for the treatment of male hypogonadism: a systematic review and meta-analysis of randomized controlled trials
- Safety and efficacy of enclomiphene and clomiphene for hypogonadal men
- Efficacy of Clomiphene Citrate Versus Enclomiphene Citrate for Male Infertility Treatment: A Retrospective Study
- Serum levels of enclomiphene and zuclomiphene in men with hypogonadism on long-term clomiphene citrate treatment
- Differential effects of isomers of clomiphene citrate on reproductive tissues in male mice (animal study)
- Long-Term Safety and Efficacy of Clomiphene Citrate for the Treatment of Hypogonadism
- Effects of clomiphene citrate on male obesity-associated hypogonadism: a randomized, double-blind, placebo-controlled study
- Characterising the safety of clomiphene citrate in male patients through prostate-specific antigen, haematocrit, and testosterone levels
- EnCyzix (enclomifene): public assessment report, EMA/88321/2018
- FDA Denies Approval of Repros Therapeutics' Enclomiphene (BioSpace)
- Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the FD&C Act (updated May 14, 2026)
- CLOMID (clomiphene citrate) tablets – prescribing information (DailyMed)
- WADA Technical Letter TL26 – Clomifene (effective 1 January 2026)
- Disruption and recovery of testicular function during and after androgen abuse: the HAARLEM study
- Factors predicting normalization of reproductive hormones after cessation of anabolic-androgenic steroids in men: a single center retrospective study
