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Polycystic Ovary Syndrome: Pathophysiology and therapeutic opportunities

Dong, Jiawen and Rees, D. Aled ORCID: 2023. Polycystic Ovary Syndrome: Pathophysiology and therapeutic opportunities. BMJ Medicine 2 , e000548. 10.1136/bmjmed-2023-000548

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Polycystic ovary syndrome (PCOS) is characterised by androgen excess and ovulatory dysfunction, and is one of the commonest endocrine disorders in women of reproductive age. PCOS arises as a result of polygenic susceptibility in combination with environmental influences that may include epigenetic alterations and in utero programming. In addition to the well-recognised clinical manifestations of hyperandrogenism and ovulatory dysfunction, women with PCOS are at increased risk of adverse mental health outcomes, pregnancy complications and cardiometabolic disease. Existing unlicensed treatments have limited efficacy, not least because drug development has been hampered by an incomplete understanding of the underlying pathophysiological processes. Advances in genetics, metabolomics and adipocyte biology have improved our understanding of key changes in neuroendocrine, enteroendocrine and steroidogenic pathways, including increased gonadotrophin-releasing hormone (GnRH) pulsatility, androgen excess, insulin resistance and alterations in the gut microbiome. 11-oxygenated androgens, with high androgenic potency, are abundant in many patients with PCOS and may mediate metabolic risk. These advances have prompted the development of new treatments, including those which target the neurokinin-kisspeptin axis upstream of GnRH, with the potential to mitigate adverse clinical sequelae and improve patient outcomes.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Publisher: BMJ Publishing Group
ISSN: 2754-0413
Date of First Compliant Deposit: 20 September 2023
Date of Acceptance: 18 September 2023
Last Modified: 27 Feb 2024 12:31

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