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Polycystic ovary syndrome as a metabolic disease

Nature Reviews Endocrinology volume 21, pages 230–244 (2025)Cite this article

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Abstract

Polycystic ovary syndrome (PCOS) is a heterogeneous familial disorder affecting up to one in five women. The aetiology remains unclear, but available evidence suggests it is a polygenic disorder with epigenetic, developmental, and environmental components. The diagnostic criteria for PCOS are based on reproductive features, and the syndrome is categorized into several phenotypes that can vary by race and ethnicity. Insulin resistance and metabolic dysfunction have a crucial role in the pathogenesis of the syndrome and contribute to many adverse metabolic outcomes that place a substantial burden on the health of women with PCOS across their lifespan. Metabolic abnormalities like those identified in women with PCOS are also present in their female and male first-degree relatives. Overall, more emphasis is required on defining PCOS as a metabolic disorder in addition to a reproductive one. This approach could affect the management and future treatment options for the syndrome. The rationale of the current review is to identify and analyse existing evidence for PCOS as a metabolic, as well as a reproductive, disease.

Key points

  • Beyond reproductive features, polycystic ovary syndrome (PCOS) is associated with an increased prevalence of several metabolic abnormalities, some of which are also observed in the first-degree relatives of women with PCOS.

  • Insulin resistance and compensatory hyperinsulinaemia, intrinsic to PCOS and exacerbated by obesity, are major drivers of metabolic complications and strong determinants of reproductive dysfunction and hyperandrogenaemia in affected women.

  • The clinical presentation of PCOS is heterogeneous and can be categorized into several phenotypes that can vary by life stage, race and/or ethnicity and degree of adiposity.

  • Cluster analysis suggests that there are reproducible reproductive and metabolic PCOS subtypes with distinct genetic architecture, which cannot be identified by the current diagnostic criteria.

  • With advances in omics-based studies and artificial intelligence-based methods, it might be possible to classify women with PCOS into subgroups that correlate with the clinical severity and identify those at high risk of long-term metabolic complications.

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Fig. 1: Pathophysiology of PCOS.
Fig. 2: Adipose tissue dysfunction in PCOS.
Fig. 3: Metabolic dysfunction in PCOS phenotypes.

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  1. Division of Endocrinology and Metabolism, Ankara Ataturk Sanatoryum Training and Research Hospital, Ankara, Turkey

    Nafiye Helvaci

  2. Division of Endocrinology and Metabolism, Department of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey

    Bulent Okan Yildiz

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Helvaci, N., Yildiz, B.O. Polycystic ovary syndrome as a metabolic disease. Nat Rev Endocrinol 21, 230–244 (2025). https://doi.org/10.1038/s41574-024-01057-w

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