POLYCYSTIC OVARY SYNDROME: ORIGINS AND IMPLICATIONS: Polycystic ovary syndrome: the impact of androgen excess on metabolic health

Abstract

In brief: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder characterised by androgen excess, which drives not only reproductive dysfunction but also significant metabolic disturbances. This review outlines the mechanistic role of classical and 11-oxygenated androgens in tissue-specific metabolic dysfunction and their progression to the metabolic manifestations seen in women with PCOS.

Abstract: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder characterised by androgen excess, reproductive dysfunction and metabolic disturbances. Beyond its reproductive implications, hyperandrogenism plays a central role in the pathogenesis of metabolic dysfunction, contributing to insulin resistance, type 2 diabetes mellitus (T2DM), metabolic-associated steatotic liver disease (MASLD) and cardiovascular disease (CVD). While classical androgens have long been implicated, increasing evidence highlights the role of peripheral androgen metabolism, particularly 11-oxygenated androgens, in driving metabolic dysregulation. Androgen excess promotes tissue-specific changes, leading to increased visceral adiposity, impaired adipocyte function, increased skeletal muscle insulin resistance and hepatic lipid accumulation and fibrosis. These metabolic perturbations are further compounded by the bidirectional relationship between insulin resistance and androgen excess, establishing a self-perpetuating cycle of metabolic dysfunction. Epidemiological and in vivo studies support a causal link between hyperandrogenism and T2DM, independent of obesity, underscoring its role as a key metabolic driver in PCOS. While the long-term cardiovascular implications of PCOS remain debated, emerging evidence suggests an increased risk of CVD, particularly in hyperandrogenic phenotypes. This review examines the mechanistic interplay between androgen excess and metabolic dysfunction in PCOS, integrating translational insights into the clinical manifestations of the metabolic disturbances increasingly recognised in PCOS.

Keywords: 11-oxygenated androgens; androgen excess; cardiovascular disease; insulin resistance; metabolic dysfunction; polycystic ovary syndrome; type 2 diabetes.