Clomiphene, 1500mg (25mg/capsule)

Clomiphene is a racemic mixture of approximately 38% enclomiphene (trans-isomer) and 62% zuclomiphene (cis-isomer). Enclomiphene is predominantly an ER antagonist with a ~10-hour half-life. Zuclomiphene is a mixed ER agonist/antagonist with a ~30-day half-life, leading to accumulation with repeated dosing.

Apex Peptides also supplies isolated enclomiphene (ENCLOMFNE-60) for studies requiring pure trans-isomer pharmacology without the zuclomiphene background.

Zuclomiphene accumulates with repeated dosing (t½ ~30 days vs. enclomiphene's ~10 hours), creating a progressively increasing background of ER agonist/antagonist activity that is difficult to control or quantify in repeat-dose study designs. This accumulation confounds attribution of pharmacodynamic effects to the enclomiphene component — the presumed primary active isomer for HPG-axis modulation.

Researchers studying acute or isomer-specific ER antagonism at the HPG axis typically prefer isolated enclomiphene to avoid this confound.

Clomiphene's primary HPG-axis mechanism is ER antagonism at hypothalamic arcuate nucleus KNDy neurons and pituitary gonadotrophs. Oestrogen-mediated negative feedback normally suppresses GnRH pulsatility and gonadotropin secretion. ER antagonism by clomiphene's enclomiphene component reduces this negative feedback, increasing GnRH pulse frequency and downstream LH/FSH secretion.

The zuclomiphene component provides a counteracting partial ER agonist background that partially offsets this effect, resulting in the net gonadotropin-stimulating profile of the racemic mixture.