Enclomiphene
Also known as: Androxal, trans-Clomifene
Selective Estrogen Receptor Modulator | Testosterone & Fertility Support
Overview
Enclomiphene is the trans-isomer of clomifene citrate, a selective estrogen receptor modulator (SERM) that acts primarily as an estrogen antagonist at the hypothalamus and pituitary. Unlike the racemic mixture clomifene (Clomid), which contains both enclomiphene and the cis-isomer zuclomifene, enclomiphene lacks significant estrogenic agonist activity. This makes it better suited for raising endogenous testosterone through increased LH and FSH secretion without the estrogenic side effects commonly associated with clomifene. It was developed under the trade name Androxal for the treatment of secondary hypogonadism in men but has not yet received FDA approval as a standalone product.
Key benefits
- Raises endogenous testosterone by stimulating the HPTA axis
- Preserves fertility and spermatogenesis (unlike exogenous testosterone)
- No estrogenic agonist activity (unlike racemic clomifene/Clomid)
- Oral dosing with no injections required
- Does not suppress the HPTA or cause testicular atrophy
- Effective for post-cycle therapy and secondary hypogonadism
- Well-tolerated with a favorable side effect profile
Mechanism of action
Enclomiphene competitively antagonizes estrogen receptors in the hypothalamus and anterior pituitary, blocking the negative feedback of estradiol on GnRH release. This disinhibition increases pulsatile GnRH secretion, which in turn stimulates the anterior pituitary to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Elevated LH drives Leydig cell testosterone synthesis in the testes, while FSH supports Sertoli cell function and spermatogenesis. Because enclomiphene lacks the estrogenic agonist properties of zuclomifene, it provides cleaner HPTA stimulation without paradoxical estrogenic effects on mood, vision, or other tissues.
Molecular data
- Type
- Trans-isomer of clomifene (selective estrogen receptor modulator)
- Half-life
- ~10 hours
Indications
What the research community uses this compound for, with self-reported effectiveness.
Testosterone Restoration
Post-Cycle Therapy
Male Fertility
Dosing protocols
Common protocols by delivery method. Adjust the curve below to model accumulation in your own cycle.
Delivery method
| Protocol | Dose | Frequency | Duration |
|---|---|---|---|
| — | 12.5mg | Once daily | — |
| — | 25mg | Once daily | — |
| — | 25mg | Once daily for 4-8 weeks | — |
| — | 50mg | Once daily for 4-6 weeks | — |
| — | 12.5-25mg | Once daily (ongoing with monitoring) | — |
Safety
Reported adverse effects, contraindications, and what to monitor on cycle.
Common side effects
- Headache
- Nausea or mild gastrointestinal discomfort
- Hot flashes or flushing
- Mood changes (irritability or emotional sensitivity)
- Fatigue during initial adjustment
Rare side effects
- Visual disturbances (blurred vision, floaters, light sensitivity)
- Elevated liver enzymes
- Thromboembolic events (very rare)
- Ovarian hyperstimulation (in females, off-label use)
Contraindications
- Known hypersensitivity to clomifene or enclomiphene
- Pre-existing liver disease or significantly elevated liver enzymes
- Active or history of thromboembolic disorders
- Pregnancy or women who may become pregnant (teratogenic risk)
- Primary hypogonadism (testicular failure -- enclomiphene requires functional testes)
- Pituitary tumors or undiagnosed pituitary pathology
References
Primary literature and clinical-trial data informing this entry.