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Cited by 131Ovarian function and disordersReproductive Biology and FertilitySexual Differentiation and Disorders

Hyperandrogenic origins of polycystic ovary syndrome-Implications for Pathophysiology and Therapy

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Abbott, David H, Dumesic, Daniel A, Levine, Jon E·2019·Expert Review of Endocrinology & Metabolism
DOI 10.1080/17446651.2019.1576522PMC PMC6992448
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Abstract

INTRODUCTION: Polycystic ovary syndrome (PCOS) diagnosis comprises combinations of female hyperandrogenism, menstrual irregularity and polycystic ovaries. While it is a familial and highly prevalent endocrine disorder, progress towards a cure is hindered by absence of a definitive pathogenic mechanism and lack of an animal model of naturally occurring PCOS. AREAS COVERED: These include an overview of PCOS and its potential etiology, and an examination of insights gained into its pathogenic origins. Animal models derived from experimentally-induced hyperandrogenism during gestation, or from naturally-occurring PCOS-like traits, most reliably demonstrate reproductive, neuroendocrine and metabolic pathogenesis. EXPERT OPINION: Genetic studies, while identifying at least 17 PCOS risk genes, account for <10% of women with PCOS. A number of PCOS risk genes involve regulation of gonadotropin secretion or action, suggesting a reproductive neuroendocrine basis for PCOS pathogenesis. Consistent with this notion, a number of animal models employing fetal androgen excess demonstrate epigenetic induction of PCOS-like traits, including reproductive neuroendocrine and metabolic dysfunction. Monkey models are most comprehensive, while mouse models provide molecular insight, including identifying the androgen receptor, particularly in neurons, as mediating androgen-induced PCOS-like programming. Naturally-occurring female hyperandrogenism is also demonstrated in monkeys. Animal models are poised to delineate molecular gateways to PCOS pathogenesis.

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  • Elevated prenatal testosterone is a well-established cause of PCOS.

    “Whereas elevated prenatal testosterone is a well‐established cause of PCOS (Abbott et al., 2019; Filippou & Homburg, 2017), understanding endometriosis as a developmental disorder involving reduced prenatal testosterone exposure is a novel contribution with diverse clinical, research, and theoretical implications.”

    From Endometriosis and polycystic ovary syndrome are diametric disorders (2021) · cites this paper as Abbott et al., 2019

    The Expert Commentary says gestational testosterone excess produces PCOS-like phenotypes in animal models, while human evidence is mostly circumstantial; it calls a hyperandrogenic developmental origin a credible pathogenic origin. The maternal-fetal environments section says a comparable pathogenic mechanism in humans remains to be demonstrated. Thus, the source supports prenatal androgen excess as a plausible contributor, not elevated prenatal testosterone as a well-established cause of human PCOS. Page numbers were not supplied. (LLM, conf=0.89)

    Experimental — accuracy not yet measured

  • Prenatal exposure to androgenic EDC (triclosan, glyphosate, tributyltin, nicotine) is of increasing concern, given the suspected epigenetic role of in utero androgen exposure in the pathogenesis of PCOS.

    “Prenatal exposure to androgenic EDC (triclosan, glyphosate, tributyltin, nicotine) is of increasing concern, given the suspected epigenetic role of in utero androgen exposure in the pathogenesis of PCOS [48,200,201].”

    From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [201]

    The Expert Commentary and “Epigenetic pathogenic origins for PCOS” sections (page numbers unavailable) support a suspected epigenetic role for gestational androgen excess in PCOS-like development. Our copy does not link prenatal exposure to triclosan, glyphosate, tributyltin, or nicotine to that mechanism, or describe concern about those exposures. (LLM, conf=0.87)

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Authors
Abbott, D. H., Dumesic, D. A., & Levine, J. E.
Affiliations
  • University of Wisconsin System (US)
  • University of California, Los Angeles (US)
  • University of Wisconsin–Madison (US)
Corresponding author
Abbott, David H
ORCID
Venue
Expert Review of Endocrinology & Metabolism
Publisher
Informa UK Limited
Published
2019-02-15
Volume
14
Issue
2
Pages
131-143
ISSN
  • 1744-6651 (ISSN-L)
  • 1744-8417
DOI
10.1080/17446651.2019.1576522
PMC
PMC6992448
OpenAlex
W2914893853
Cited by
131
References
181
Citations by year
2026: 6 · 2025: 7 · 2024: 22 · 2023: 18 · 2022: 27 · 2021: 20 · 2020: 16 · 2019: 13 · 2018: 2
FWCI
2.68
Type
journal article
Language
en
Open access
Locations
  • Expert Review of Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
NIH (: P50 HD028934, P50 HD044405, P50 HD071836, P51 ODO11092 and UL1TR001881)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
Keywords
polycystic ovary syndrome, hyperandrogenism, PCOS pathogenesis, epigenetic programming, androgen receptor, gonadotropin regulation, neuroendocrine dysfunction, metabolic dysfunction, monkey model, mouse model, menstrual irregularity
MeSH terms
Animals, Disease Models, Animal, Female, Genetic Testing, Humans, Maternal-Fetal Exchange, Polycystic Ovary Syndrome, Pregnancy, Hyperandrogenism, Epigenesis, Genetic

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