Cited by 132Ovarian function and disordersGenetic and Kidney Cyst DiseasesEndometriosis Research and Treatment

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Causes and Consequences of Polycystic Ovary Syndrome: Insights From Mendelian Randomization

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Zhu, Tiantian, Goodarzi, Mark O·2022·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/clinem/dgab757PMC PMC8852214

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Abstract

Context: Although polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age, risk factors that may cause the syndrome are poorly understood. Based on epidemiologic studies, PCOS is thought to cause several adverse outcomes such as cardiovascular disease; however, the common presence of comorbidities such as obesity may be responsible for such associations, rather than PCOS in and of itself. To overcome the limitations of observational studies, investigators have employed Mendelian randomization (MR), which uses genetic variants to interrogate causality between exposures and outcomes. Evidence Acquisition: To clarify causes and consequences of PCOS, this review will describe MR studies involving PCOS, both as an exposure and as an outcome. The literature was searched using the terms “Mendelian randomization,” “polycystic ovary syndrome,” “polycystic ovarian syndrome,” and “PCOS” (to May 2021). Evidence Synthesis: MR studies have suggested that obesity, testosterone levels, fasting insulin, serum sex hormone-binding globulin concentrations, menopause timing, male-pattern balding, and depression may play a causal role in PCOS. In turn, PCOS may increase the risk of estrogen receptor–positive breast cancer, decrease the risk of endometrioid ovarian cancer, and have no direct causal effect on type 2 diabetes, coronary heart disease, or stroke. Conclusions: The accumulation of genome-wide association studies in PCOS has enabled multiple MR analyses identifying factors that may cause PCOS or be caused by PCOS. This knowledge will be critical to future development of measures to prevent PCOS in girls at risk as well as prevent complications in those who have PCOS.

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Authors: Zhu, T., & Goodarzi, M. O.
Affiliations: Cedars-Sinai Medical Center (US)
Corresponding author: Goodarzi, Mark O
ORCID: Zhu, Tiantian
Goodarzi, Mark O
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2021-10-20
Volume: 107
Issue: 3
Pages: e899-e911
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/clinem/dgab757
PMC: PMC8852214
OpenAlex: W3205635727
Cited by: 126
References: 53
Citations by year: 2026: 19 · 2025: 33 · 2024: 41 · 2023: 25 · 2022: 7 · 2021: 1
FWCI: 3.28
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Center for Advancing Translational Sciences (UL1TR000124)
National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (P30-DK063491)
Eris M. Field Chair in Diabetes Research
Topics: Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
Keywords: polycystic ovary syndrome, causality, obesity, testosterone, insulin, sex hormone-binding globulin, menopause timing, androgenetic alopecia, depression, estrogen receptor-positive breast cancer, endometrioid ovarian cancer, type 2 diabetes, coronary artery disease, stroke, PCOS prevention
MeSH terms: Breast Neoplasms, Depression, Female, Humans, Ovarian Neoplasms, Polycystic Ovary Syndrome, Risk Factors, Causality, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Mendelian Randomization Analysis

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Causes and Consequences of Polycystic Ovary Syndrome: Insights From Mendelian Randomization

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