Cussen Leanne, McDonnell Tara, Miller Clare, McIlroy Marie, O'Reilly Michael W
Reproduction. 2025 Jul 4;170(2). doi: 10.1530/REP-25-0102. Print 2025 Aug 1.
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.
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.
多囊卵巢综合征（PCOS）是一种复杂的内分泌紊乱疾病，其特征为雄激素过多，这不仅会导致生殖功能障碍，还会引发显著的代谢紊乱。本综述概述了经典雄激素和11-氧化雄激素在组织特异性代谢功能障碍中的作用机制，以及它们如何发展为PCOS女性中所见的代谢表现。
多囊卵巢综合征（PCOS）是一种复杂的内分泌紊乱疾病，其特征为雄激素过多、生殖功能障碍和代谢紊乱。除了对生殖的影响外，高雄激素血症在代谢功能障碍的发病机制中起核心作用，导致胰岛素抵抗、2型糖尿病（T2DM）、代谢相关脂肪性肝病（MASLD）和心血管疾病（CVD）。虽然经典雄激素长期以来一直被认为与之有关，但越来越多的证据表明外周雄激素代谢，特别是11-氧化雄激素，在驱动代谢失调方面发挥着作用。雄激素过多会促进组织特异性变化，导致内脏脂肪增加、脂肪细胞功能受损、骨骼肌胰岛素抵抗增加以及肝脏脂质蓄积和纤维化。胰岛素抵抗和雄激素过多之间的双向关系进一步加剧了这些代谢紊乱，形成了一个自我延续的代谢功能障碍循环。流行病学和体内研究支持高雄激素血症与T2DM之间存在因果关系，且独立于肥胖，强调了其作为PCOS关键代谢驱动因素的作用。虽然PCOS对心血管的长期影响仍存在争议，但新出现的证据表明CVD风险增加，尤其是在高雄激素表型中。本综述探讨了PCOS中雄激素过多与代谢功能障碍之间的机制相互作用，将转化医学见解整合到PCOS中日益被认识到的代谢紊乱的临床表现中。
