Vol. 7, Issue 1, Part A (2025)

Polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic disorder affecting up to 10% of reproductive-age women globally. Central to its pathophysiology is the disruption of gonadotropin-releasing hormone (GnRH) pulsatility, which skews luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion, favoring hyperandrogenism and anovulation. This neuroendocrine imbalance is further amplified by insulin resistance and hyperinsulinemia—common metabolic features of PCOS—that disrupt hypothalamic signaling and contribute to excessive ovarian androgen production. Despite advances in clinical management, most current therapies focus on symptom mitigation rather than addressing the central neuroendocrine dysfunction. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), primarily used in type 2 diabetes and obesity, are emerging as promising agents that bridge metabolic regulation with reproductive endocrinology. This review synthesizes evidence implicating GLP-1 in modulating GnRH neuron excitability, potentially restoring physiological pulsatility patterns. By improving insulin sensitivity, reducing androgen excess, and promoting weight loss, GLP-1 RAs offer a multifaceted therapeutic strategy. Their impact on LH: FSH dynamics, SHBG elevation, and free androgen reduction underscores their dual metabolic and reproductive benefits. Furthermore, emerging data suggest their ability to normalize menstrual cyclicity and enhance fertility outcomes, especially in phenotypes with significant metabolic burden. The review advocates for targeted interventions that integrate neuroendocrine and metabolic modulation, highlighting GLP-1 RAs as a next-generation approach in PCOS management. Further randomized controlled trials are essential to validate their efficacy in modulating GnRH pulsatility and optimizing reproductive health.