INTRODUCTION: Polycystic ovary syndrome (PCOS) is a prevalent multisystem disorder with major reproductive and metabolic consequences. Understanding the interconnected molecular pathways linking insulin resistance (IR), hyperinsulinemia, and hyperandrogenism is crucial, as these mechanisms form the foundation for effective clinical management and targeted therapeutic strategies. AREAS COVERED: This review examines current evidence on the metabolic underpinnings of PCOS, focusing on how IR and compensatory hyperinsulinemia alter ovarian steroidogenesis, impair granulosa cell aromatase activity, and disrupt follicular development. We summarize downstream systemic consequences-including dyslipidemia, impaired glucose tolerance, cardiovascular risk, and nonalcoholic fatty liver disease-while integrating emerging data on environmental disruptors, oxidative stress, and adipose tissue dysfunction. Literature was identified through a comprehensive search of PubMed, Scopus, Google Scholar, and ScienceDirect for studies published between 1985 and 2025, including clinical, experimental, and mechanistic work relevant to metabolic aspects of PCOS. EXPERT OPINION: Clarifying the metabolic and endocrine mechanisms driving both reproductive and systemic dysfunction provides a critical basis for developing targeted therapies capable of improving ovulatory function and long-term cardiometabolic outcomes. Deepening mechanistic insight remains essential for advancing individualized and integrative treatment approaches in this heterogeneous and evolving syndrome.
Pappas et al. (2026) studied this question.