Enclomifene

Hormonal / PCT

Also known as: Androxal, Enclomiphene, Enclomiphene Citrate, trans-Clomifene

Selective Estrogen Receptor ModulatorsResearch phase: Phase 3Regulatory: Not FDA-approved. Received FDA Complete Response Letter. Available through compounding pharmacies and telehealth clinics.

Mechanism

Enclomifene is the purified active isomer of clomifene, isolated to provide cleaner anti-estrogenic effects without the weakly estrogenic zuclomifene isomer found in Clomid. It completed Phase 3 trials for male secondary hypogonadism, showing consistent testosterone elevation while preserving fertility — unlike exogenous testosterone which suppresses sperm production.

Technical detail

Enclomifene (trans-clomifene) is the pharmacologically active anti-estrogenic isomer of clomifene, purified to eliminate the zuclomifene isomer's confounding weak estrogenic activity and longer half-life. It selectively antagonizes ER at the hypothalamus and pituitary, increasing GnRH pulsatility and LH/FSH secretion. Phase 3 trials (ZA-304, ZA-305) in men with secondary hypogonadism demonstrated normalization of morning testosterone in ~75% of subjects while maintaining or improving sperm parameters. FDA issued a Complete Response Letter citing manufacturing and clinical concerns, and approval has not been granted.

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