Enclomiphene citrate is the trans isomer of clomiphene citrate, a non-steroidal estrogen receptor antagonist.Clomiphene citrate is a mixture of two diastereoisomers, (cis) Zuclomiphene citrate (38%) and (trans) Enclomiphene citrate (62%). The commercial name for Enclomiphene citrate is Androxal®. Studies comparing Enclomiphene, Zuclomiphene, and clomiphene found clinically important pharmacologic differences between the three. Zuclomiphene, an estrogen receptor agonist, caused estrogenic side effects often reported with clomiphene use. Additionally, Zuclomiphene was found to have a longer half-life (30 days) when compared to clomiphene citrate (10 hours), resulting in persistent side effects lasting beyond the therapeutic effects of the drug. In contrast, Enclomiphene was identified as the isomer that raises LH and FSH levels, with a shorter half-life. This led to the hypothesis that treatment with Enclomiphene should have more favorable outcomes in treating androgen deficient men with the goal of maintaining fertility, potentially without the side effects associated with clomiphene citrate use and with a more favorable impact on hypogonadal symptoms.
Clomiphene citrate works at the level of the hypothalamus to block estradiol's negative feedback on GnRH production—thus leading to an increase in the secretion of GnRH and subsequently LH and FSH. The hypothalamic-pituitary-testicular axis function must be preserved for CC or EC to be effective.