Clomifene: A Comprehensive Monograph on its Pharmacology, Clinical Utility, and Evolving Therapeutic Landscape

I. Introduction and Executive Summary

Clomifene is a nonsteroidal triphenylethylene stilbene derivative that holds a seminal position in the history of reproductive medicine.[1] As a pioneering Selective Estrogen Receptor Modulator (SERM), it was the first widely adopted oral agent for the induction of ovulation.[3] Its approval by the United States Food and Drug Administration (FDA) in 1967 marked a paradigm shift, effectively launching the modern era of assisted reproductive technology by providing a simple, accessible treatment for anovulatory infertility.[3] For over half a century, clomifene has been a cornerstone therapy for millions of individuals seeking to conceive.

The primary mechanism of clomifene involves its action as an estrogen receptor antagonist within the hypothalamus. By blocking the negative feedback of endogenous estrogen, it stimulates an increased pulsatile release of gonadotropin-releasing hormone (GnRH), which in turn prompts the pituitary gland to secrete higher levels of Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH). This surge in gonadotropins drives ovarian follicular development, maturation, and ultimately, ovulation.[5] Consequently, its principal clinical indication is the treatment of anovulatory or oligo-ovulatory infertility, particularly in women with Polycystic Ovary Syndrome (PCOS).[1] It is also widely used, though largely in an off-label capacity, for the treatment of certain forms of male infertility by enhancing endogenous testosterone and sperm production.[9]