Enclomiphene is the trans-isomer of clomiphene (Clomid), sold as a separate compound. Like clomiphene, it is a selective estrogen receptor modulator (SERM): it blocks estrogen’s brake on the pituitary, so LH and FSH rise and the testes make more testosterone and sperm. In two Phase 3 trials in overweight men with low testosterone, it raised testosterone and kept sperm counts in the normal range, while testosterone gel lowered them (Kim 2016).

No regulator has approved it. FDA issued a complete response letter in 2015, the EU refused a license in 2018, and the trials never showed an improvement in symptoms (EMA 2018). This page covers the trials, the regulatory history, side effects, how it compares with clomiphene and testosterone, and what is known about using it with or after SARMs.

Enclomiphene at a glance

What it is SERM; the trans-isomer of clomiphene. Other names: enclomifene, Androxal, EnCyzix
What it does Raises LH, FSH and the body’s own testosterone; keeps sperm production
Studied in Men with secondary hypogonadism (low testosterone with low or normal LH), mostly overweight
Furthest stage Phase 3; marketing applications filed in the US and EU, not approved
Half-life About 8–10 hours (EMA 2018)
Sport Banned at all times as an isomer of clomifene (WADA S4.2) (WADA 2026)

How enclomiphene works

How Does Enclomiphene Therapy Work

The pituitary releases LH and FSH when it senses low hormone levels; estrogen is one of the signals that holds it back. Enclomiphene blocks estrogen receptors there, so LH and FSH rise. LH drives testosterone production in the testes and FSH drives sperm production. FDA’s 2022 review describes the same mechanism (FDA 2022).

Testosterone therapy works the other way round: it supplies testosterone from outside, which shuts LH and FSH down. That is why gel lowered sperm counts in the head-to-head trials and enclomiphene did not (Kim 2016).

Why one isomer? Clomiphene contains both enclomiphene and zuclomiphene. Zuclomiphene clears very slowly and builds up: in men on long-term clomiphene its blood level was about 20 times that of enclomiphene (Helo 2017). In male mice, zuclomiphene harmed reproductive tissues while enclomiphene raised testosterone without those changes (Fontenot 2016, animal study). Giving enclomiphene alone avoids the build-up.

Regulatory history

Date What happened
Dec 2015 Repros Therapeutics announced an FDA complete response letter for Androxal: FDA said the Phase 3 design was no longer adequate to show clinical benefit and recommended more Phase 3 work (BioSpace).
25 Jan 2018 EMA’s CHMP gave a negative opinion on EnCyzix for overweight men with hypogonadotropic hypogonadism (EMA).
6 Apr 2018 EU marketing authorization refused. Reasons: benefit on symptoms was not shown, and a risk of blood clots (EMA).
8 Jun 2022 FDA’s Pharmacy Compounding Advisory Committee voted 4 yes, 8 no on adding enclomiphene citrate to the 503A bulks list; the no votes cited a lack of efficacy evidence (FDA minutes).
14 May 2026 FDA’s 503A list still shows enclomiphene citrate in Category 1, “under evaluation” (FDA).
2026 UK: unlicensed. The British Society for Sexual Medicine says use should be limited to experienced clinicians, ideally in research settings (BSSM 2026).

What the trials found

Most of the trials below were run by the drug’s developer, and several were never published as full papers.

Trial Who Dose and length Result
Phase 2 vs testosterone gel (Wiehle 2013) 44 men with secondary hypogonadism 6.25, 12.5 or 25 mg/day, 6 weeks All doses raised testosterone and LH. At 25 mg/day, morning testosterone was 604 ± 160 ng/dL vs 500 ± 278 on gel. IGF-1 fell more on enclomiphene
Phase 2b, placebo and gel (Wiehle 2014); results posted as NCT01270841 83 men with secondary hypogonadism 12.5 or 25 mg/day, 3 months Testosterone change: +258.5 ng/dL (12.5 mg), +197.3 (25 mg), +253.7 (gel), −16.9 (placebo). LH and FSH rose on enclomiphene and fell on gel
Phase 3 ZA-304 and ZA-305 (EMA 2018) Overweight men aged 18–60 with acquired hypogonadotropic hypogonadism 12.5 mg/day, raised to 25 mg/day at week 4 if testosterone stayed below 450 ng/dL; 16 weeks Testosterone in range plus sperm ≥10 million/mL: 61.0% and 65.9% on enclomiphene vs 16.3% on gel. Sperm below 10 million/mL: 1 of 41 and 1 of 44 men vs 19 of 43 and 10 of 42 on gel
Phase 3 ZA-301 (EMA 2018) Overweight men, placebo-controlled 12.5 mg/day, raised to 25 mg/day if needed 78.8% (89 of 113) reached a normal 24-hour average testosterone
Open-label safety study ZA-300 (NCT01534208) 499 men 12.5 mg/day, escalated to 25 mg/day; 6 months Morning testosterone at 26 weeks: 511.6 ng/dL (stayed on 12.5 mg) and 416.7 ng/dL (escalated). Serious adverse events in 15 of 490 men
With diet and exercise (NCT02651688) 50 men 12.5 or 25 mg/day, 48 weeks Posted results: testosterone +173.8 and +237.2 ng/dL vs +43.3 on placebo; lean mass +3.1 and +2.4 kg vs +1.1 kg. No peer-reviewed paper found

Independent data are newer and observational. In a retrospective study of 46 men on enclomiphene and 32 on clomiphene, both raised testosterone, but only enclomiphene significantly raised LH, FSH and total motile sperm count (Thomas 2023). A 2025 meta-analysis of randomized trials found that clomiphene and enclomiphene raised total testosterone by about 274 ng/dL vs placebo and did not differ from gel (Hohl 2025).

What has not been shown

  • Symptoms. The pivotal trials measured hormones and sperm, not symptoms such as libido, energy or bone health. Both EMA and FDA said clinical benefit on symptoms was not shown (FDA 2022).
  • Fertility outcomes. FDA noted that semen results alone do not prove fertility (FDA 2022).
  • Long-term safety. Most randomized trials ran 6 to 16 weeks. One small randomized study ran 48 weeks but has only posted results, not a paper (NCT02651688), and the longest open-label study ran 6 months.
  • Use after steroids or SARMs. A 2026 review says enclomiphene has not been validated in steroid-induced hypogonadism (Bandura 2026).

Side effects

Side effect What the evidence says Evidence
Headache, hot flushes, nausea, muscle spasm The most frequent adverse events in EMA’s review. Events that led people to stop included blurred vision, muscle spasm, headache and aggression (FDA 2022). Trial
Rates in a 6-month study Headache 35 of 490 men, upper respiratory infection 53, muscle spasms 22, hot flush 11 (ZA-300). Trial
Blood clots Four thromboembolic events in men taking enclomiphene (one DVT with pulmonary embolism, two DVTs, one fatal ischemic stroke), none on testosterone or placebo. All four had other risk factors. EMA judged the risk important and cited it in the refusal (EMA 2018). Trial
Blurred vision, cataract “Vision blurred” 0.5% vs 0% and “cataract” 0.3% vs 0% in pooled trials. EMA found no conclusive evidence that it causes cataracts but asked for eye-safety monitoring (EMA 2018). Trial
Raised hematocrit, PSA and estradiol Listed by EMA as safety concerns shared with testosterone therapy (EMA 2018). Trial
Erectile dysfunction, aggression Erectile dysfunction 0.6% vs 0% on gel or placebo (EMA 2018). Trial
Atrial flutter One case in a man with prior heart valve surgery who took 50 mg/day by mistake; causality rated “possible” (Tariq 2026). Case report
Organ toxicity in animals High doses affected rat prostate, testes and kidneys; high-dose dog deaths were linked to liver toxicity. Not seen in human trials (FDA 2022). Animal

Lipids, TSH, cortisol and bone markers did not change significantly over 6 weeks in the Phase 2 study (Wiehle 2013).

Enclomiphene vs clomiphene vs testosterone gel

Enclomiphene Clomiphene Testosterone gel
Testosterone Rises (own production) Rises (own production) Supplied from outside
LH and FSH Rise Rise Fall
Sperm counts Kept (1 of 41 below 10 million/mL) Kept in studies Fell (19 of 43 below 10 million/mL)
Estradiol −5.9 pg/mL after switching (one clinic) +17.5 pg/mL (same clinic) (Saffati 2024) Not compared here
Approved Nowhere Women only (1967) Yes, for men with hypogonadism (Bhasin 2018)
Half-life 8–10 h Zuclomiphene part lingers for weeks Not applicable

In the 66-man clinic study, testosterone rose by a median 166 ng/dL on enclomiphene vs 98 on clomiphene (not significant), and side effects were reported less often on enclomiphene (Saffati 2024). No randomized head-to-head trial exists. More: clomiphene for men.

Enclomiphene with SARMs, and as PCT

Some people take enclomiphene during or after a SARM cycle to keep LH and testosterone up. No study has tested either use.

  • During a cycle: SARMs push LH and testosterone down through the androgen receptor; enclomiphene pushes LH up through the estrogen receptor. Nobody has measured what happens when both are taken. LGD-4033 lowered testosterone even at 0.1–1 mg/day in its trial (Basaria 2013).
  • After a cycle: the post-steroid PCT data are for clomiphene, not enclomiphene (İbis 2026), and a 2026 review says enclomiphene has not been validated for this (Bandura 2026).

Compound-by-compound suppression data: SARMs PCT. Timelines and markers: PCT & Bloodwork Planner.

Doses used in studies

Trials used 6.25, 12.5 and 25 mg/day. The Phase 3 trials started at 12.5 mg/day and raised the dose to 25 mg/day in men whose testosterone stayed below 450 ng/dL at week 4 (EMA 2018). These are study doses in men with secondary hypogonadism, not recommendations. The effect on testosterone outlasted the drug: levels stayed up for at least a week after stopping in one trial (Wiehle 2013).

One caution from EMA’s review: people who are CYP2D6 poor metabolizers had about 5 times higher peak levels and 7 times higher overall exposure (EMA 2018).

Bloodwork measured in the trials

The trials and EMA’s safety review tracked total testosterone, LH, FSH, estradiol, hematocrit and PSA, plus semen analysis where fertility mattered. These are the markers the research used, not a monitoring plan. What each one means and typical ranges: SARMs bloodwork.

Where Status
United States Not FDA-approved. Listed in 503A Category 1 (under evaluation); compounded products need a prescription (FDA).
European Union Marketing authorization refused in 2018; not an authorized medicine (EMA).
United Kingdom Unlicensed (BSSM 2026).
Germany Clomifen, including its isomers, is in the Anti-Doping Act annex (AntiDopG).
Sport Prohibited at all times (WADA S4.2, as clomifene). WADA’s 2026 technical letter counts zuclomifene and enclomifene together, with a 2.0 ng/mL reporting level in urine (WADA TL26).

Where to buy enclomiphene

Enclomiphene is not an approved medicine anywhere. Sarmguide’s current pick for research-grade enclomiphene is SwissChems Enclomiphene 12.5 mg, 60 capsules, sold for laboratory research use with third-party lab results per batch. See Buy PCT and the SwissChems review.

Bottom line

Enclomiphene does what it was designed to do in the trials: it raises testosterone through the body’s own system and keeps sperm counts. What it has not done is win approval, because the trials did not show symptom benefit and raised a blood-clot signal. For use with or after SARMs there are no data at all. Related: 13 things to know about SERMs, SARMs database.

Charts

Doses used in human studies of Enclomiphene What the published studies used and found. These are research doses reported in the studies, not recommendations. Dots mark each dose a study tested (per-kg doses are listed in the table only).
Doses used in human studies of Enclomiphene44 men (2013): 6.3–25 mg; 83 men (2014): 13–25 mg; Overweight men (2018): 13–25 mg; Overweight men (2018): 13–25 mg; 499 men (2013): 13–25 mg; 50 men (2017): 13–25 mg0 mg10 mg20 mg30 mg44 men (2013)44 men (2013): 6.3–25 mg6.3–25 mg83 men (2014)83 men (2014): 13–25 mg13–25 mgOverweight men (2018)Overweight men (2018): 13–25 mg13–25 mgOverweight men (2018)Overweight men (2018): 13–25 mg13–25 mg499 men (2013)499 men (2013): 13–25 mg13–25 mg50 men (2017)50 men (2017): 13–25 mg13–25 mg
Dose studiedWho took partDurationWhat the study foundSource
6.25, 12.5 or 25 mg/day44 men with secondary hypogonadism (per-protocol), vs transdermal testosterone gel6 weeksAll doses raised testosterone and LH. At 25 mg/day, morning total testosterone was 604 ± 160 ng/dL vs 500 ± 278 ng/dL on gel. Gel suppressed LH. IGF-1 fell more with enclomiphene.PubMed 2013
12.5 or 25 mg/day83 men with secondary hypogonadism; placebo and topical testosterone (Testim) arms (NCT01270841)3 monthsMean change in morning testosterone: +258.5 ng/dL (12.5 mg), +197.3 ng/dL (25 mg), +253.7 ng/dL (gel), −16.9 ng/dL (placebo). LH and FSH rose on enclomiphene and fell on gel.PubMed 2014
12.5 mg/day, raised to 25 mg/day at week 4 if morning testosterone was below 450 ng/dLOverweight men (BMI 25–42) aged 18–60 with acquired hypogonadotropic hypogonadism; two Phase 3 trials (ZA-304, ZA-305) vs AndroGel 1.62% and placebo16 weeksComposite success (testosterone 300–1040 ng/dL and sperm ≥10 million/mL): 61.0% (ZA-304) and 65.9% (ZA-305) on enclomiphene vs 16.3% on gel in both trials. Sperm concentration fell below 10 million/mL in 1 of 41 and 1 of 44 men on enclomiphene vs 19 of 43 and 10 of 42 on gel.ema.europa.eu 2018
12.5 mg/day, raised to 25 mg/day if neededOverweight men with acquired hypogonadotropic hypogonadism, placebo-controlled Phase 3 (ZA-301)12 weeks (18 weeks if up-titrated)89 of 113 men (78.8%) on enclomiphene reached a 24-hour average testosterone in the normal range (300–1040 ng/dL).ema.europa.eu 2018
12.5 mg/day, escalated to 25 mg/day if needed499 men with secondary hypogonadism, open-label safety study (ZA-300, NCT01534208)6 monthsMean morning testosterone at 26 weeks: 511.6 ng/dL (stayed on 12.5 mg) and 416.7 ng/dL (escalated to 25 mg). LH and FSH rose. Serious adverse events in 15 of 490 men.clinicaltrials.gov 2013
12.5 or 25 mg/day with diet and exercise50 men with acquired hypogonadotropic hypogonadism, placebo-controlled (NCT02651688)48 weeksPosted results: testosterone rose by 173.8 ng/dL (12.5 mg) and 237.2 ng/dL (25 mg) vs 43.3 ng/dL on placebo. Lean mass rose 3.1 kg and 2.4 kg vs 1.1 kg on placebo. No peer-reviewed paper of this trial was found.clinicaltrials.gov 2017

Sources: the studies linked in the table.

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Half-life of Enclomiphene compared Elimination half-life in people, where measured (log scale; bars show the reported range). Values from different studies and routes are not directly comparable.
Half-life of Enclomiphene comparedTesamorelin: ~8–11 min; Ipamorelin: ~2 h; Enclomiphene: ~8–10 h; Clomiphene: ~5–24 h (No single value: enclomiphene part ~5–10 h; zuclomiphene part ~24 h with a very long tail (detectable for over a month)); Ostarine: ~14–24 h; LGD-4033: ~24–36 h (24–36 h); RAD-140: ~45 h; Anastrozole: ~2–2.1 days (~50 h); Tamoxifen: ~5–7 days (~5–7 days (tamoxifen); ~14 days (N-desmethyltamoxifen, main active metabolite)); CJC-1295: ~5.8–8.1 days (~6–8 days)6 min30 min1 h3 h6 h12 h1 day3 days1 weekTesamorelinTesamorelin: ~8–11 min~8–11 minIpamorelinIpamorelin: ~2 h~2 hEnclomipheneEnclomiphene: ~8–10 h~8–10 hClomipheneClomiphene: ~5–24 h (No single value: enclomiphene part ~5–10 h; zuclomiphene part ~24 h with a very long tail (detectable for over a month))~5–24 hOstarineOstarine: ~14–24 h~14–24 hLGD-4033LGD-4033: ~24–36 h (24–36 h)~24–36 hRAD-140RAD-140: ~45 h~45 hAnastrozoleAnastrozole: ~2–2.1 days (~50 h)~2–2.1 daysTamoxifenTamoxifen: ~5–7 days (~5–7 days (tamoxifen); ~14 days (N-desmethyltamoxifen, main active metabolite))~5–7 daysCJC-1295CJC-1295: ~5.8–8.1 days (~6–8 days)~5.8–8.1 days

Source: Sarmguide compound database; Enclomiphene value: EnCyzix (enclomifene): public assessment report, EMA/88321/2018 (2018).

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More on Enclomiphene

Frequently asked questions

Is enclomiphene a SARM?

No, a SERMEvidence: Human data

Enclomiphene, the trans-isomer of clomiphene, blocks estrogen feedback at the pituitary, which raises LH, FSH and the body's own testosterone. SARMs act on the androgen receptor instead.

Read the full section

Is enclomiphene FDA-approved?

NoEvidence: Law

FDA did not approve it after a 2015 complete response letter, and EMA refused a European license in 2018. As of May 2026 FDA still lists it as under evaluation (503A Category 1).

Read the full section

Does enclomiphene raise testosterone?

Yes, in trialsEvidence: Trial

In one Phase 3 trial in men with secondary hypogonadism, 78.8% reached a normal 24-hour average testosterone. The trials did not show improvement in symptoms.

Read the full section

What is the difference between enclomiphene and clomiphene?

One isomer vs a mix of twoEvidence: Human data

Clomiphene is a mix of enclomiphene and zuclomiphene (30–50% zuclomiphene, according to the label); enclomiphene is one isomer on its own. Zuclomiphene builds up: in men on long-term clomiphene its level was about 20 times that of enclomiphene.

Read the full section

Does enclomiphene affect sperm count or fertility?

Sperm counts were kept in trialsEvidence: Trial

In two 16-week Phase 3 trials, sperm fell below 10 million/mL in 1 of 41 and 1 of 44 men on enclomiphene, vs 19 of 43 and 10 of 42 on testosterone gel. FDA notes that semen results alone do not prove fertility.

Read the full section

What side effects were reported with enclomiphene?

Headache, hot flushes, clot signalEvidence: Trial

The most common were headache, hot flushes, nausea and muscle spasm. EMA also found a signal for blood clots (four events in men taking it), more blurred vision, and rises in hematocrit, PSA and estradiol.

Read the full section

Can you take enclomiphene with SARMs?

Not studiedEvidence: Limited

SARMs lower LH and testosterone through the androgen receptor; enclomiphene raises LH through the estrogen receptor. What happens when both are taken has not been measured, and both are banned in sport.

Read the full section

Is enclomiphene used for PCT after steroids or SARMs?

Some use it; not testedEvidence: Limited

No trial has tested it, and a 2026 review says enclomiphene has not been validated in steroid-induced hypogonadism. The post-steroid PCT data are for clomiphene.

Read the full section

How long does enclomiphene stay in your system?

Half-life about 8–10 hoursEvidence: Human data

EMA gives a plasma half-life of about 8–10 hours, with at least 90% of a dose expected to leave the body within 14 days. Its effect on testosterone outlasted the drug by at least a week in one trial.

Read the full section

What doses of enclomiphene were used in studies?

6.25 to 25 mg a dayEvidence: Trial

Trials used 6.25, 12.5 and 25 mg per day; the Phase 3 trials started at 12.5 mg/day and raised it to 25 mg/day in men whose testosterone stayed low. These are study doses, not recommendations.

Read the full section

Is enclomiphene banned in sport?

Yes, at all timesEvidence: Law

WADA lists clomifene under S4.2, prohibited at all times, and enclomifene is one of its isomers. WADA's 2026 technical letter counts zuclomifene and enclomifene together when reporting clomifene in urine.

Read the full section

Sources

  1. Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: restoration instead of replacement 2016 · PMID 26496621
  2. Refusal of the marketing authorisation for EnCyzix (enclomifene), EMA/CHMP/54473/2018 2018
  3. EnCyzix (enclomifene): public assessment report, EMA/88321/2018 2018
  4. World Anti-Doping Code International Standard: Prohibited List 2026 2025
  5. FDA Pharmacy Compounding Advisory Committee transcript, June 8, 2022 2022
  6. Serum levels of enclomiphene and zuclomiphene in men with hypogonadism on long-term clomiphene citrate treatment 2017 · PMID 27511863
  7. Differential effects of isomers of clomiphene citrate on reproductive tissues in male mice (animal study) 2016 · PMID 26220499
  8. FDA Denies Approval of Repros Therapeutics' Enclomiphene (BioSpace) 2015
  9. EnCyzix | European Medicines Agency 2018
  10. Final Summary Minutes of the Pharmacy Compounding Advisory Committee Meeting, June 8, 2022 2022
  11. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the FD&C Act (updated May 14, 2026) 2026
  12. British Society of Sexual Medicine: Position Statement for the Potential Use of Enclomiphene in the Treatment of Male Hypogonadism 2026 · PMID 41714894
  13. Testosterone Restoration by Enclomiphene Citrate in Men with Secondary Hypogonadism: Pharmacodynamics and Pharmacokinetics 2013 · PMID 23875626
  14. Enclomiphene citrate stimulates testosterone production while preventing oligospermia: a randomized phase II clinical trial comparing topical testosterone 2014 · PMID 25044085
  15. ClinicalTrials.gov NCT01270841: Normalization of Morning Testosterone Levels in Men With Secondary Hypogonadism (Phase 2, posted results) 2014
  16. ClinicalTrials.gov NCT01534208: Safety Study of Enclomiphene Citrate in the Treatment of Men With Secondary Hypogonadism (results) 2013
  17. ClinicalTrials.gov NCT02651688: Body composition and metabolic parameters with diet and exercise plus 12.5 mg or 25 mg enclomiphene (results) 2017
  18. Efficacy of Clomiphene Citrate Versus Enclomiphene Citrate for Male Infertility Treatment: A Retrospective Study 2023 · PMID 37546076
  19. Clomiphene or enclomiphene citrate for the treatment of male hypogonadism: a systematic review and meta-analysis of randomized controlled trials 2025 · PMID 41066380
  20. Clomiphene Citrate in off-Label Post-Cycle Therapy: Mechanisms, Efficacy and Diagnostic Challenges in Endocrine Recovery Following Anabolic Steroid Use 2026 · PMID 42387872
  21. Newly Detected Atrial Flutter After Enclomiphene Dose Escalation in a Patient With Prior Mitral Valve Repair and Chronic Immune Thrombocytopenia: A Case Report 2026 · PMID 42741668
  22. Safety and efficacy of enclomiphene and clomiphene for hypogonadal men 2024 · PMID 39434750
  23. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline 2018 · PMID 29562364
  24. The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men 2013 · PMID 22459616
  25. Post-cycle therapy after short-term anabolic-androgenic steroid use: comparative outcomes in recreational bodybuilders 2026 · PMID 41147237
  26. Anlage zum Anti-Doping-Gesetz (AntiDopG), BGBl. 2023 I Nr. 67 2023
  27. WADA Technical Letter TL26 – Clomifene (effective 1 January 2026) 2025