Enclomiphene (Androxal)
Pure trans-isomer of clomiphene – Repros Therapeutics 2014-2016 Phase III hypogonadism candidate. Cleaner SERM profile than Clomid (zuclomiphene-free), BUT FDA CRL 2016 → not approved. Available via US-compounding + EU research-pharm.
WHAT IS ENCLOMIPHENE (ANDROXAL)?
Detailed overview
Enclomiphene (Androxal) is the pure trans-isomer of Clomid (clomiphene citrate) – eliminating the zuclomiphene half that is the main culprit behind Clomid's mood disturbance. Developed by Repros Therapeutics 2007-2014 for oral treatment of male secondary hypogonadism, the Phase III ZA-301 + ZA-302 trials (Wiehle 2014 PMID 24913480, Wiehle 2018 PMID 30015376) demonstrated efficacy at 12.5-25 mg/day (T <300 ng/dL → T >450 ng/dL) + spermatogenesis preservation. The Phase III primary endpoint (T >450 ng/dL) was met in both low- and high-dose arms; however, the FDA Complete Response Letter (CRL) in 2016 requested additional efficacy + safety data, and Repros – due to financial trouble – never resubmitted (2018 bankruptcy). In 2026 Enclomiphene is NOT FDA-approved; US-compounding pharmacy + EU research-pharmacy availability, UGL liquid formulations also exist. AAS-PCT relevance: cleaner mood profile than Clomid, preserves spermatogenesis (vs Test replacement which suppresses it). Off-label TRT alternative in male secondary hypogonadism (fertility-preservation goal).
Mechanism
Pure trans-isomer clomiphene, ER-α antagonist at pituitary, NO zuclomiphene mood effect
Dosing (PCT or hypogonadism)
12.5-25 mg/day, morning
Half-life
~5 days (cleaner than Clomid mixed t1/2)
Onset
LH rise 24-72 h, Test recovery 2-4 weeks
Legal status
NOT FDA-approved (CRL 2016), US-compounding + EU research-pharm + UGL
Data console
Lab data
Safety
Side effects, stop signs, contraindications
Side effects · 7
- Visual disturbances: blurred vision, light flashes (photopsia), glare. A known SERM-class effect from retinal ER modulation – rarer and milder than with Clomid, but persistent symptoms warrant immediate discontinuation.
- Elevated estradiol (E2): the increased LH raises testicular testosterone and, via aromatization, can raise E2, presenting as water retention, mood swings and rarely gynecomastia.
- Headache: the most commonly reported adverse event in the Phase III trials, usually mild and transient.
- Mood swings, irritability: markedly rarer and milder than with Clomid (the zuclomiphene isomer is absent), but not fully eliminated – emotional lability and irritability can occur.
- Nausea and gastrointestinal discomfort: GI upset can occur and is reduced by taking the dose with a morning meal.
- Venous thromboembolism risk: estrogen-receptor modulation carries a prothrombotic effect across the SERM class; deep vein thrombosis and pulmonary embolism risk exists, especially with predisposing factors.
- Unknown long-term safety profile: the FDA Complete Response Letter (2016) was issued precisely over missing long-term cardiovascular, bone and prostate data; chronic use (>3 months) safety is unproven.
Contraindications · 6
- Pregnancy and teratogenicity: clomiphene compounds are contraindicated in pregnancy (Pregnancy Category X); heightened caution is needed if a female partner could conceive. Risk of fetal harm in women.
- Prior or active thromboembolism: avoid in deep vein thrombosis, pulmonary embolism, stroke history or known thrombophilia due to the prothrombotic effect of SERMs.
- Active or severe liver disease: a relative contraindication in active hepatic dysfunction due to hepatic metabolism; liver function monitoring required.
- Hormone-sensitive tumor: avoid in estrogen- or androgen-dependent tumors (e.g. prostate cancer) or undiagnosed abnormal genital bleeding.
- Primary (hypergonadotropic) hypogonadism: efficacy depends on an intact HPTA and functioning testes; it is ineffective and not indicated in primary testicular failure (high LH/FSH).
- Competitive athletes: listed on the WADA S4 prohibited list (hormone and metabolic modulators, SERMs), banned in and out of competition for men.
Related Performance Compounds
Same therapeutic category
Studies
Related research and clinical findings
Enclomiphene citrate stimulates testosterone production while preventing oligospermia: a randomized phase II clinical trial comparing topical testosterone.
Wiehle RD, Fontenot GK, Wike J, Hsu K, Nieschlag E, Saadabadi A
Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: restoration instead of replacement.
Kim ED, McCullough A, Kaminetsky J
Oral enclomiphene citrate stimulates the endogenous production of testosterone and sperm counts in men with low testosterone: comparison with testosterone gel.
Kaminetsky J, Werner M, Fontenot G, Wiehle RD
Anabolic steroid-induced hypogonadism: diagnosis and treatment.
Rahnema CD, Lipshultz LI, Crosnoe LE, Kovac JR, Kim ED
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The information here is for educational and scientific purposes only. Performance-enhancing compounds (AAS, prohormones, stimulants, doping agents) are illegal without prescription in Hungary and most of the EU, and carry serious health and legal risks. WADA bans them in competitive sport. This is NOT a usage guide, and we do not encourage any illegal use. If you do use them, medical supervision and regular bloodwork are ESSENTIAL. Severe endocrine, cardiovascular, hepatic and psychiatric side effects are possible.