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Review
. 2025 Mar 24;169(4):e250021.
doi: 10.1530/REP-25-0021. Print 2025 Apr 1.

POLYCYSTIC OVARY SYNDROME: ORIGINS AND IMPLICATIONS: Polycystic ovary syndrome: an evolutionary metabolic adaptation

Daniel A Dumesic, Vasantha Padmanabhan, David H Abbott
Review

POLYCYSTIC OVARY SYNDROME: ORIGINS AND IMPLICATIONS: Polycystic ovary syndrome: an evolutionary metabolic adaptation

Daniel A Dumesic et al. Reproduction. .

Abstract

In brief: Polycystic ovary syndrome has ancient genetic origins that favored preferential abdominal fat accumulation, ovarian hyperandrogenism and insulin resistance. This review examines how endocrine-metabolic changes in normal-weight hyperandrogenic PCOS women originated as an evolutionary metabolic adaptation to balance enhanced fat storage with increased glucose and fatty acid availability for optimal energy use for survival and reproduction.

Abstract: Polycystic ovary syndrome (PCOS) is a common endocrinopathy of reproductive-aged women, characterized by hyperandrogenism, oligo-anovulation and insulin resistance in combination with preferential abdominal fat accumulation. As an ancestral primate trait, PCOS in humans likely underwent relatively recent preferential selection when scarcity of food in hunter-gatherers of the Pleistocene selected for enhanced fat storage and insulin resistance as a survival advantage to maintain glucose homeostasis for brain and reproductive function. As an evolutional model for PCOS, healthy normal-weight women with hyperandrogenic PCOS have subcutaneous (SC) abdominal adipose stem cells that favor exaggerated lipid accumulation during adipocyte development in vitro accompanied by reduced systemic insulin sensitivity and preferential accumulation of highly lipolytic intra-abdominal fat. Programmed by genetic inheritance and epigenetic events during early life, such a metabolic adaptation in PCOS, provides a balance between enhanced SC adipose fat storage and increased circulating glucose and free fatty acid availability as energy substrate for crucial target tissues. The accompanying increased muscle strength and oligo-anovulation in PCOS women of antiquity also enabled sustained energy use during endurance activities in combination with greater time as a rearing advantage for children and a lower risk of maternal mortality. Heritable PCOS characteristics that originally evolved in primates as a genetically and epigenetically enhanced metabolic adaptation to favor fat storage now predispose to lipotoxicity and pregnancy complications, calling for improved preventive healthcare, with early lifestyle and therapeutic choices to optimize the long-term health of PCOS women and their children in today's obesogenic environment.

Keywords: androgen heritability; fat metabolism; hyperandrogenism; polycystic ovary syndrome.

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Conflict of interest statement

Declaration of Interest (potential conflict of interest)

D.A.D has consulted for Spruce Biosciences Inc, Precede Biosciences Inc, Ferring Research Institute, Ferring Pharmaceuticals, and Organon LLC. D.H.A. declares no conflicts of interest, financial or otherwise. V.P. declares no conflicts of interest, financial or otherwise. VP is an editor for this special series and serves on the Editorial board of Reproduction. She was not involved in the peer review process of this article on which she is listed as an author.

This paper forms part of a special series on Polycystic Ovary Syndrome: Origins and Implications. The Guest Editors for this special series are Professor Daniel A Dumesic (David Geffen School of Medicine at UCLA, Los Angeles, CA, USA), Professor Emerita (in service) Vasantha Padmanabhan (University of Michigan, Ann Arbor MI, USA), and Professor David H. Abbott (University of Wisconsin and Wisconsin National Primate Research Center, Madison, WI, USA.

References

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