Enclomiphene Reference

Reference summary

Wiehle 2013 BJU Int demonstrated that enclomiphene citrate raises endogenous LH, FSH, and testosterone in secondary hypogonadism men with a pharmacokinetic and pharmacodynamic profile distinct from racemic clomiphene. The argument for enclomiphene over racemic clomiphene is that the zuclomiphene isomer is the longer-half-life estrogen-receptor-agonist component of racemic clomiphene; the enclomiphene-only isomer should produce cleaner antagonist-driven gonadotropin elevation. Phase 3 outcome data for the regulatory submission were the basis of the 2015 FDA non-approval.

Regulatory and posture

Categories

Hormonal, Reproductive

Aliases

Androxal (investigational; not FDA-approved as a single agent), Trans-isomer of clomiphene citrate, Selective estrogen receptor modulator (small molecule, not a peptide)

Evidence posture

human - Investigational; FDA non-approval in 2015. Available only as off-label compounded product in the US.

Regulatory status

Not FDA-approved as a single-agent product for any indication. The Androxal program (Repros Therapeutics) targeted secondary hypogonadism in men but failed Phase 3 FDA approval in 2015 due to the trial design and FDA-identified concerns with the secondary-hypogonadism endpoint framework. Available in the United States only as off-label compounded enclomiphene; the trans-isomer is not separately marketed as a finished pharmaceutical product. WADA-prohibited at all times under S4 (hormone and metabolic modulators).

Content review status

research reference