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Metabolic dysfunction in polycystic ovary syndrome: Pathogenic role of androgen excess and potential therapeutic strategies

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Sanchez-Garrido, Miguel A., Tena-Sempere, Manuel·2020·Molecular Metabolism
DOI 10.1016/j.molmet.2020.01.001PMC PMC7115104
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Abstract

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among reproductive age women. Although its cardinal manifestations include hyperandrogenism, oligo/anovulation, and/or polycystic ovarian morphology, PCOS women often display also notable metabolic comorbidities. An array of pathogenic mechanisms have been implicated in the etiology of this heterogeneous endocrine disorder; hyperandrogenism at various developmental periods is proposed as a major driver of the metabolic and reproductive perturbations associated with PCOS. However, the current understanding of the pathophysiology of PCOS-associated metabolic disease is incomplete, and therapeutic strategies used to manage this syndrome's metabolic complications remain limited. SCOPE OF REVIEW: This study is a systematic review of the potential etiopathogenic mechanisms of metabolic dysfunction frequently associated with PCOS, with special emphasis on the metabolic impact of androgen excess on different metabolic tissues and the brain. We also briefly summarize the therapeutic approaches currently available to manage metabolic perturbations linked to PCOS, highlighting current weaknesses and future directions. MAJOR CONCLUSIONS: Androgen excess plays a prominent role in the development of metabolic disturbances associated with PCOS, with a discernible impact on key peripheral metabolic tissues, including the adipose, liver, pancreas, and muscle, and very prominently the brain, contributing to the constellation of metabolic complications of PCOS, from obesity to insulin resistance. However, the current understanding of the pathogenic roles of hyperandrogenism in metabolic dysfunction of PCOS and the underlying mechanisms remain largely incomplete. In addition, the development of more efficient, even personalized therapeutic strategies for the metabolic management of PCOS patients persists as an unmet need that will certainly benefit from a better comprehension of the molecular basis of this heterogeneous syndrome.

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  • Any diet that guarantees weight loss can improve insulin resistance, hyperandrogenism and fertility in women with polycystic ovary syndrome.

    “It is important to highlight that any diet that guarantees weight loss can improve IR, hyperandrogenism and fertility in PCOS women.”

    From Low-Calorie Ketogenic Diet: Potential Application in the Treatment of Polycystic Ovary Syndrome in Adolescents (2023) · cites this paper as [7]

    The “Lifestyle interventions and pharmacological approaches” section says diet and exercise aimed at weight loss are recommended and that weight reduction improves metabolic homeostasis and hyperandrogenism in women with PCOS. It does not establish that any weight-loss diet improves insulin resistance and fertility; the reproductive improvements it describes are linked to treatments such as metformin, not diet alone. No page number is available in our copy. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • The ketogenic diet has attracted significant interest for the treatment of insulin resistance and for the control of carbohydrate metabolism, and has proven beneficial for several dysmetabolic conditions, including polycystic ovary syndrome.

    “Recently, the ketogenic diet (KD) has attracted significant interest for the treatment of IR and for the control of carbohydrate metabolism, which has proven to be beneficial for several dysmetabolic conditions, including PCOS.”

    From Low-Calorie Ketogenic Diet: Potential Application in the Treatment of Polycystic Ovary Syndrome in Adolescents (2023) · cites this paper as [7]

    Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

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  • The obesity-induced metabolic impact of the polycystic ovary syndrome phenotype appears to be reversible after weight loss.

    “The obesity-induced metabolic impact of PCOS phenotype appears to be reversible after weight loss [7].”

    From Low-Calorie Ketogenic Diet: Potential Application in the Treatment of Polycystic Ovary Syndrome in Adolescents (2023) · cites this paper as [7]

    The Introduction says obesity exacerbates metabolic complications in PCOS, and the Lifestyle interventions section says weight reduction improves metabolic homeostasis. The Bariatric surgery section also reports improved metabolic measures after surgery, but the paper does not establish that the obesity-related metabolic impact is fully reversed after weight loss. No page numbers are available in our copy. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • The majority of women with PCOS manifest multiple metabolic features including obesity, insulin resistance, hyperlipidemia and hyperandrogenism.

    “The majority of women with PCOS manifest multiple metabolic features including obesity, insulin resistance (IR), hyperlipidemia and hyperandrogenism [19,20].”

    From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [19]

    The Introduction says a large proportion of women with PCOS are obese or overweight, and the insulin-resistance section reports IR in 65–70% of patients. It also identifies hyperandrogenism as a PCOS feature and dyslipidemia as a metabolic comorbidity, but does not establish that a majority have all four listed features or specifically have hyperlipidemia rather than dyslipidemia. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Experimental studies in primates, sheep, rats and mice show that PCOS-like syndromes can be induced by a range of treatments including androgens, anti-Mullerian hormone and letrozole.

    “Experimental studies in primates, sheep, rats and mice show that PCOS-like syndromes can be induced by a range of treatments including androgens, anti-Mullerian hormone and letrozole [19,44,46].”

    From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [19]

    The Developmental factors section reports that prenatal androgen exposure induces PCOS-like phenotypes in monkeys, sheep, rats and mice. It also describes a mouse model in which gestational anti-Müllerian hormone exposure may cause a PCOS-like reproductive phenotype. The passages do not support the letrozole part of the claim (searched: letrozole); page numbers were unavailable. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Sanchez-Garrido, M. A., & Tena-Sempere, M.
Affiliations
Instituto de Salud Carlos III (ES)
Corresponding author
Sanchez-Garrido, Miguel A.
ORCID
Sanchez-Garrido, Miguel A.
Venue
Molecular Metabolism
Publisher
Elsevier BV
Published
2020-05
Volume
35
Pages
100937
ISSN
2212-8778 (ISSN-L)
DOI
10.1016/j.molmet.2020.01.001
PMC
PMC7115104
OpenAlex
W3005398252
Cited by
557
References
31
Citations by year
2026: 86 · 2025: 106 · 2024: 110 · 2023: 95 · 2022: 89 · 2021: 53 · 2020: 16 · 2018: 1
FWCI
9.36
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Metabolism (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • RISalud Institutional Health Repository of Andalucía (submittedVersion, cc-by-nc-nd)
  • UTUPub (University of Turku) (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Universidad de Córdoba
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
Keywords
polycystic ovary syndrome, metabolic dysfunction, hyperandrogenism, insulin resistance, obesity, adipose tissue, liver, pancreas, skeletal muscle, brain, PCOS pathogenesis
MeSH terms
Adipose Tissue, Androgens, Animals, Female, Humans, Insulin Resistance, Obesity, Polycystic Ovary Syndrome, Hyperandrogenism, Metabolic Syndrome, Bariatric Surgery, Mice

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