Enclomiphene, developed by Repros Therapeutics Inc, is a nonsteroidal estrogen receptor antagonist that promotes testosterone secretion by increasing levels of gonadotropin produced by the testes.

Enclomiphene constitutes the trans-stereoisomer of clomiphene citrate, a widely prescribed drug for several decades for the treatment of female ovulatory dysfunction.

Because of enclomiphene’s antagonistic effects, the drug has the potential to increase serum testosterone levels in men with secondary hypogonadism by restoring endogenous physiological testosterone secretion while maintaining testicular volume and, potentially, spermatogenesis.

In clinical trials to date, enclomiphene has shown significant efficacy in physiological restoration of testosterone levels in males with secondary hypogonadism.

The compound has also shown an unexpected favorable effect on fasting blood glucose; this finding has been accompanied by the rapid accumulation of evidence from other investigators of a bidirectional relationship between low serum testosterone levels and obesity/metabolic syndrome (syndrome X) in men.

Short-term clinical safety data for enclomiphene were satisfactory and equivalent to safety data for testosterone gel and placebo.

Enclomiphene shows promise in the management of secondary hypogonadism associated with obesity, metabolic syndrome, and possibly infertility and should undergo randomized placebo-controlled clinical trials for these indications.

In the ‘enanched bodybuilding setting, enclomiphene comes as post cycle therapy (PCT) to replace clomiphene and tamoxifen.

Compared to the latter, enclomiphene demonstrates fewer side effects and greater efficacy.