Enclomiphene

Also known as: enclomiphene, enclomiphene citrate, trans-clomiphene

Hormone Restoration

In plain English

Enclomiphene is the more active part of clomiphene, refined to raise a man's own testosterone while helping keep sperm production intact. It is used off-label as an alternative to testosterone replacement for men who want to preserve fertility. It is taken as a capsule. It is not currently an FDA-approved product.

The science

Enclomiphene is the trans-isomer of clomiphene, a selective estrogen receptor modulator that antagonizes hypothalamic estrogen feedback to raise LH, FSH, and endogenous testosterone. Compared with clomiphene it lacks the long-acting estrogenic zuclomiphene isomer. Phase 2 pharmacodynamic/pharmacokinetic and clinical trials (Wiehle 2013, 2014) demonstrated restoration of morning testosterone into the normal range with preserved—or increased—gonadotropins and conserved sperm counts, in contrast to topical testosterone which suppressed spermatogenesis. Despite favorable trial data, enclomiphene is not FDA-approved (its new drug application was not approved), so all use is via compounding and is off-label. Adverse effects mirror SERM class effects (headache, mood changes, rare visual symptoms); long-term outcome and safety data are limited.

References

• Wiehle et al., Fertil Steril 2014 (enclomiphene phase II RCT vs topical T)
• Wiehle et al., BJU Int 2013 (pharmacodynamics/pharmacokinetics)