Causes and Consequences of Polycystic Ovary Syndrome: Insights From Mendelian Randomization
Open accessAbstract
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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Preliminary evidence suggests that several genes related to obesity, metabolic and reproductive function may play a causal role in the pathogenesis of PCOS.
“Nevertheless, preliminary evidence suggests that several genes related to obesity, metabolic and reproductive function, may play a causal role in the pathogenesis of PCOS [90,91].”
From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [90]
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SINDROM POLICISTIČNIH JAJČNIKOV, LAKTOGENEZA IN DOJENJE
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- Authors
- Zhu, T., & Goodarzi, M. O.
- Affiliations
- Cedars-Sinai Medical Center (US)
- Corresponding author
- 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
- 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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