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Characterizing skeletal muscle dysfunction in women with polycystic ovary syndrome

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Polycystic ovary syndrome (PCOS) is the most common endocrine condition affecting women. It has traditionally been viewed as a primarily reproductive disorder; however, it is increasingly recognized as a lifelong metabolic disease. Women with PCOS are at increased risk of insulin resistance (IR), type 2 diabetes mellitus, non-alcoholic fatty liver disease and cardiovascular disease. Although not currently a diagnostic criterion, IR is a cardinal pathophysiological feature and highly prevalent in women with PCOS. Androgens play a bidirectional role in the pathogenesis of IR, and there is a complex interplay between IR and androgen excess in women with PCOS. Skeletal muscle has a key role in maintaining metabolic homeostasis and is also a metabolic target organ of androgen action. Skeletal muscle is the organ responsible for the majority of insulin-mediated glucose disposal. There is growing interest in the relationship between skeletal muscle, androgen excess and mitochondrial dysfunction in the pathogenesis of metabolic disease in PCOS. Molecular mechanisms underpinning defects in skeletal muscle dysfunction in PCOS remain to be elucidated, but may represent promising targets for future therapeutic intervention. In this review, we aim to explore the role of skeletal muscle in metabolism, focusing particularly on perturbations in skeletal muscle specific to PCOS as observed in recent molecular and in vivo human studies. We review the possible role of androgens in the pathophysiology of skeletal muscle abnormalities in PCOS, and identify knowledge gaps, areas for future research and potential therapeutic implications. Despite increasing interest in the area of skeletal muscle dysfunction in women with PCOS, significant challenges and unanswered questions remain, and going forward, novel innovative approaches will be required to dissect the underlying mechanisms.

Funding

HRB Emerging Clinician Scientist Award (ECSA-2020-001)

History

Comments

The original article is available at https://journals.sagepub.com/

Published Citation

McDonnell T, Cussen L, McIlroy M, O'Reilly MW. Characterizing skeletal muscle dysfunction in women with polycystic ovary syndrome. Ther Adv Endocrinol Metab. 2022;13:20420188221113140.

Publication Date

18 July 2022

PubMed ID

35874313

Department/Unit

  • Medicine
  • Surgery
  • Beaumont Hospital

Research Area

  • Endocrinology
  • Cancer

Publisher

SAGE Publications

Version

  • Published Version (Version of Record)