The DOI matches its Crossref record; 49 of the 51 references it cites were found in a registry or an index.
Developmental origin of polycystic ovary syndrome—a hypothesis
Open accessAbstract
Polycystic ovary syndrome (PCOS) is a common but complex endocrine disorder and is a major cause of anovulation and consequent subfertility. It is also associated with a metabolic disturbance, characterized by hyperinsulinaemia and insulin resistance that carries an increased risk of type 2 diabetes in later life. Despite its prevalence little is known about its aetiology, but there is increasing evidence for an important genetic involvement. On the basis of experimental observations in the prenatally androgenized sheep and rhesus monkey, and supported by data from human studies, we propose that the clinical and biochemical features of PCOS can arise as a consequence of genetically determined hypersecretion of androgens by the ovary during, or very likely long before, puberty. The resulting hyperandrogenism results in 'programming' of the hypothalamic-pituitary unit to favour excess LH secretion, and encourages preferential abdominal adiposity that predisposes to insulin resistance. The severity of hyperinsulinaemia and insulin resistance (which has a profound influence on the phenotype of PCOS) is further influenced by both genetic factors (such as polymorphism in the insulin gene regulatory region) and environmental factors, notably obesity. This hypothesis therefore suggests a unifying, 'linear' model to explain the aetiology of the heterogeneous phenotype.
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“Dietary and environmental factors are hypothesized to have an impact on developmental programming of susceptible gene variants in women with PCOS [41,42,43].”
From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [42]
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“In keeping with this model, multiple lines of evidence suggest that inherited PCOS gene variants are developmentally programmed in a way that primes them for activation by nutritional and environmental factors in postnatal life [41,42,98].”
From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [42]
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“Fetal, neonatal, prepubertal, and/or pubertal ovaries may be genetically predisposed to increased androgen secretion [100, 101].”
From Polycystic Ovary Syndrome: Pathophysiology, Presentation, and Treatment With Emphasis on Adolescent Girls (2019) · cites this paper as [100]
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The Diagnosis of Polycystic Ovary Syndrome during Adolescence
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Witchel, S. F., Oberfield, S. E., & Peña, A. S. (2019) · Journal of the Endocrine Society · doi:10.1210/js.2019-00078 · Cited by 653
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Self-citation
Metadata
- Authors
- Abbott, D., Dumesic, D., & Franks, S.
- Affiliations
- University of Wisconsin–Madison (US)
- University of London (GB)
- ORCID
- Franks, S
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2002-07-01
- Volume
- 174
- Issue
- 1
- Pages
- 1-5
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2130933461
- Cited by
- 504
- References
- 51
- Citations by year
- 2026: 13 · 2025: 9 · 2024: 13 · 2023: 12 · 2022: 17 · 2021: 17 · 2020: 15 · 2019: 24 · 2018: 20 · 2017: 21 · 2016: 24 · 2015: 23 · 2014: 22 · 2013: 30 · 2012: 23
- FWCI
- 3.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Reproductive Medicine › Reproductive Biology and Fertility
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
- Keywords
- polycystic ovary syndrome, etiology, developmental programming, prenatal androgen exposure, hyperandrogenism, ovary, luteinizing hormone secretion, insulin resistance, hyperinsulinemia, type 2 diabetes, obesity, anovulation, subfertility, sheep, rhesus monkeys
- MeSH terms
- Androgens, Animals, Female, Humans, Insulin, Insulin Resistance, Luteinizing Hormone, Macaca mulatta, Ovarian Diseases, Polycystic Ovary Syndrome, Pregnancy, Prenatal Exposure Delayed Effects, Sheep
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