Enclomiphene

Enclomiphene is the trans-isomer of clomiphene citrate, isolated from the racemic mixture that also contains zuclomiphene (the cis-isomer). While traditional clomiphene (Clomid) contains both isomers, enclomiphene is preferred because zuclomiphene has a much longer half-life and accumulates, potentially causing estrogenic side effects. Enclomiphene acts as a selective estrogen receptor modulator (SERM), blocking estrogen receptors in the hypothalamus and pituitary. By blocking estrogen's negative feedback at the hypothalamus, enclomiphene increases GnRH pulse frequency, which stimulates LH and FSH release from the pituitary. This results in increased endogenous testosterone production while maintaining — or even improving — spermatogenesis.

This makes enclomiphene an attractive option for men who want to optimize testosterone levels while preserving fertility, or as an alternative to TRT for men with secondary hypogonadism. It can also be used alongside TRT at low doses to maintain gonadotropin signaling.