Enclomiphene Citrate: A Comprehensive Clinical and Pharmacological Review for the Treatment of Secondary Male Hypogonadism

Section 1: Pharmacological Profile of Enclomiphene Citrate

The therapeutic potential and clinical profile of any pharmaceutical agent are fundamentally dictated by its chemical structure and its interaction with biological systems. Enclomiphene citrate is a prime example of rational drug design, where a specific stereoisomer of an existing compound was isolated to optimize therapeutic effects while minimizing undesirable actions. This section delineates the fundamental pharmacological identity of enclomiphene citrate, covering its chemical nature, its precise mechanism as a Selective Estrogen Receptor Modulator (SERM), and its distinct pharmacokinetic properties. Understanding these foundational elements is crucial for appreciating its clinical applications and differentiating it from its parent compound, clomiphene citrate.

1.1. Chemical Identity and Isomeric Specificity

Enclomiphene citrate is the citrate salt of enclomiphene, a nonsteroidal compound belonging to the triphenylethylene group.[1] Its chemical formula is $C_{26}H_{28}ClNO \cdot C_{6}H_{8}O_{7}$.[3] The defining characteristic of enclomiphene is its stereochemistry; it is specifically the (E)-stereoisomer, or trans-isomer, of the compound clomiphene.[1] This isomeric specificity is not a minor chemical detail but is, in fact, the central principle underlying its development as a distinct therapeutic agent.

Its parent compound, clomiphene citrate (marketed as Clomid), is an FDA-approved medication for female infertility that exists as a racemic mixture of two distinct stereoisomers: enclomiphene (the trans-isomer) and zuclomiphene (the (Z)- or cis-isomer).[5] In this mixture, enclomiphene constitutes approximately 62% of the total drug substance, while zuclomiphene makes up the remaining 38%.[1]