Polycystic Ovary Syndrome as a Multi-System Disorder: A Comprehensive Review of Hormonal, Metabolic, and Inflammatory Crosstalk at the Cellular and Molecular Level

Background-Polycystic ovary syndrome (PCOS) is a prevalent and complex endocrine disorder affecting reproductive-aged women. It is characterized by reproductive, metabolic, and psychological manifestations, with pathophysiology involving genetic, hormonal, metabolic, and inflammatory crosstalk. Despite significant research advances, the heterogeneity of PCOS continues to challenge effective diagnosis and management. Objective- This review aims to provide a comprehensive overview of the cellular, molecular, and systemic mechanisms underlying PCOS, with emphasis on hormonal, metabolic, and inflammatory interactions. It also highlights clinical manifestations, therapeutic implications, and research gaps to guide future strategies. Methods- A narrative synthesis was conducted by reviewing literature from PubMed, Scopus, and Web of Science databases. Studies addressing pathophysiology, hormonal and metabolic mechanisms, immune and inflammatory crosstalk, clinical consequences, and therapeutic interventions in PCOS were included. Priority was given to recent high-impact studies, systematic reviews, and international guidelines. Results- The findings reveal that PCOS arises from the interplay of hypothalamic-pituitary-ovarian (HPO) axis dysfunction, hyperandrogenism, insulin resistance, chronic low-grade inflammation, and gut microbiota dysbiosis. At the cellular level, theca and granulosa cell dysfunction, impaired insulin signalling, mitochondrial dysfunction, and altered adipose–liver–ovary communication contribute to disease progression. Clinically, PCOS is associated with reproductive abnormalities, metabolic syndrome, cardiovascular risks, endometrial dysfunction, and psychological consequences. Current therapies—lifestyle modification, insulin sensitizers, oral contraceptives, and anti-androgens—offer partial relief, while emerging therapies such as GLP-1 agonists, AMPK activators, mTOR inhibitors, and microbiota-targeted strategies show promise. Research gaps include the need for integrative omics, systems biology approaches, patient-specific therapies, and longitudinal studies. Conclusion- PCOS is a multi-system disorder with interlinked endocrine, metabolic, and immune axes. Understanding the cellular and molecular underpinnings is crucial for developing holistic, precision-based, and long-term management strategies. A multidisciplinary approach is required to improve reproductive, metabolic, and psychological outcomes in affected women.