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ResearchEnclomiphene

Enclomiphene vs Clomiphene for Secondary Hypogonadism | What the Evidence Shows

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dr_pepper154 Trust

May 14, 2026

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Most discussions conflate clomiphene and enclomiphene but they have meaningfully different pharmacological profiles. Clomiphene is a racemic mixture: enclomiphene (trans-isomer) and zuclomiphene (cis-isomer). The estrogenic side effects commonly reported - visual disturbances, mood changes, gyno risk - are largely attributable to zuclomiphene, which has a much longer half-life (30 days vs 10 hours for enclomiphene). Enclomiphene selectively blocks hypothalamic and pituitary estrogen receptors, restoring LH and FSH pulsatility without the accumulating estrogenic burden. Phase 3 trials showed testosterone restoration in 75-85% of secondary hypogonadal men at 12.5-25mg daily. Key practical implications: - Enclomiphene clears rapidly - cleaner cycling than clomiphene - Lower estrogenic side effect burden for longer protocols - Maintains fertility unlike TRT - Not FDA approved but widely available as research compound
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