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

in Reproduction
Authors:
Daniel A Dumesic Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

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https://orcid.org/0000-0003-0387-1277
,
Vasantha Padmanabhan Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA

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, and
David H Abbott Department of Obstetrics and Gynecology, University of Wisconsin and Wisconsin National Primate Research Center, Madison, Wisconsin, USA

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Correspondence should be addressed to D A Dumesic: ddumesic@mednet.ucla.edu

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.

DOI:
https://doi.org/10.1530/REP-25-0021
Volume/Issue:
Volume 169: Issue 4
Article ID:
e250021
Article Type:
Review Article
Online Publication Date:
24 Mar 2025
Copyright:
© the author(s) 2025
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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.

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Print ISSN:
1470-1626
Online ISSN:
1741-7899

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