POLYCYSTIC OVARY SYNDROME (PCOS) WITH PATHOPHYSIOLOGY AND EMERGING THERAPIES

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder that affects approximately 8–13% of women of reproductive age worldwide, depending on the diagnostic criteria and population studied.[1] Clinically, it is defined by the presence of hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology, after exclusion of other related conditions.[2] PCOS is associated with significant reproductive, metabolic, and psychological complications, extending far beyond fertility concerns. Insulin resistance, present even in lean phenotypes, plays a central role in amplifying hyperandrogenism and disrupting folliculogenesis, ultimately leading to chronic anovulation.[3] This interplay contributes to long-term consequences including obesity, type 2 diabetes mellitus, dyslipidaemia, cardiovascular risk, and an increased likelihood of endometrial pathology.[4] Over the past decade, advances in research and international guideline updates have shaped the diagnostic framework and therapeutic strategies for PCOS. The 2023 International Evidence-Based Guideline reaffirmed the Rotterdam criteria for adults, clarified adolescent diagnostic parameters, and emphasized the role of anti-Müllerian hormone (AMH) as a marker of polycystic ovarian morphology in adults, but not as a stand-alone diagnostic test.[5] Management continues to rely on lifestyle modification as the cornerstone of therapy, combined oral contraceptives for cycle regulation and hyperandrogenism, and letrozole as first-line pharmacological treatment for anovulatory infertility. Metformin remains an important adjunct for insulin resistance and metabolic risk reduction. In recent years, novel pharmacotherapies such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium–glucose cotransporter 2 (SGLT2) inhibitors have demonstrated promise in improving metabolic parameters and weight management, though further large-scale studies are required to confirm their long-term safety and reproductive benefits. This review explores the pathophysiological mechanisms underlying PCOS, synthesizes existing literature, and evaluates current and emerging therapeutic options with a focus on clinical translation and future research directions.