Evolutionary determinants of polycystic ovary syndrome: part 2
Open accessAbstract
Polycystic ovary syndrome (PCOS) is a prehistoric complex genetic trait, perhaps dating back at least 50,000 years. The disorder also represents an evolutionary paradox, demonstrating clear reproductive disadvantages (i.e., lack of evolutionary fitness), albeit persisting tens of thousands of years. Here we examine possible explanations for this paradox. We evaluate a variety of possible benefits accruing to women in ancestral populations who possessed this trait, including considerations of whether dramatic changes in environment and lifestyle from the ancestral past to the contemporary present have altered the selection dynamics operating on the trait. Putative benefits include metabolic functioning, immune system dynamics, patterns of child-rearing and mothering, reproductive longevity, in utero or childhood survival, and musculoskeletal advantages. However, there is limited evidence that the persistence and relative homogeneity in the prevalence of PCOS can be accounted for by direct positive selection. Rather, PCOS evolution has likely been driven by nonadaptive evolutionary mechanisms, including genetic drift due to a serial founder effect and population balance due to sexually antagonistic selection. Ultimately, insights into the evolutionary origins of PCOS will emerge through the study not only of unique characteristics of affected individuals and their environments butalso through a broad consideration of the potential adaptive and beneficial aspects of vulnerability to the disorder, importantly including examination of populations whose fertility, disease load, and diet resemble those of ancestral humans.
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Several genetic variants are similar in both Han Chinese and European populations, implying that PCOS is an ancient disease.
“Several genetic variants are similar in both Han Chinese and European populations, implying that PCOS is an ancient disease [117].”
From Polycystic Ovary Syndrome: Pathophysiology, Presentation, and Treatment With Emphasis on Adolescent Girls (2019) · cites this paper as [117]
Cites
On aims and methods of ethology
Tinbergen, N. (1963) · Zeitschrift für Tierpsychologie · doi:10.1111/j.1439-0310.1963.tb01161.x · Cited by 4,551 · see citing works
Amenorrhea associated with bilateral polycystic ovaries
Stein, I. F., & Leventhal, M. L. (1935) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(15)30642-6 · Cited by 2,121 · see citing works
Criteria, Prevalence, and Phenotypes of Polycystic Ovary Syndrome
Lizneva, D., Suturina, L., Walker, W., Brakta, S., Gavrilova-Jordan, L., & Azziz, R. (2016) · Fertility and Sterility · doi:10.1016/j.fertnstert.2016.05.003 · Cited by 1,358 · see citing works
Self-citationHeritability of polycystic ovary syndrome in a Dutch twin-family study
Vink, J. M., Sadrzadeh, S., Lambalk, C. B., & Boomsma, D. I. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-1494 · Cited by 647 · see citing works
Tinbergen's four questions: an appreciation and an update
Bateson, P., & Laland, K. N. (2013) · Trends in Ecology & Evolution · doi:10.1016/j.tree.2013.09.013 · Cited by 481 · see citing works
The Molecular-Genetic Basis of Functional Hyperandrogenism and the Polycystic Ovary Syndrome
Escobar-Morreale, H. F., Luque‐Ramírez, M., & Millán, J. L. S. (2005) · Endocrine Reviews · doi:10.1210/er.2004-0004 · Cited by 420 · see citing works
Long-term consequences of polycystic ovary syndrome: Results of a 31 year follow-up study
Wild, S. H., Pierpoint, T., Jacobs, H. S., & McKeigue, P. (2000) · Human Fertility · doi:10.1080/1464727002000198781 · Cited by 301 · see citing works
Rook, G. A. W. (2009) · Immunology · doi:10.1111/j.1365-2567.2008.03007.x · Cited by 295 · see citing works
Positive selection on the human genome
Vallender, E. J. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh253 · Cited by 246 · see citing works
Bushman birth spacing: A test for optimal interbirth intervals
Jones, N. B. (1986) · Ethology and Sociobiology · doi:10.1016/0162-3095(86)90002-6 · Cited by 227 · see citing works
The evolution of prolonged life after reproduction
Croft, D. P., Brent, L. J. N., Franks, D. W., & Cant, M. A. (2015) · Trends in Ecology & Evolution · doi:10.1016/j.tree.2015.04.011 · Cited by 203 · see citing works
Helminths as governors of immune-mediated inflammation
Elliott, D. E., Summers, R. W., & Weinstock, J. V. (2006) · International Journal for Parasitology · doi:10.1016/j.ijpara.2006.12.009 · Cited by 192 · see citing works
Grandmothers and the evolution of human longevity: A review of findings and future directions
Hawkes, K., & Coxworth, J. E. (2013) · Evolutionary Anthropology Issues News and Reviews · doi:10.1002/evan.21382 · Cited by 169 · see citing works
Polycystic ovary syndrome: An ancient disorder?
Azziz, R., Dumesic, D. A., & Goodarzi, M. O. (2011) · Fertility and Sterility · doi:10.1016/j.fertnstert.2010.09.032 · Cited by 164 · see citing works
Self-citationEvolutionary perspectives on the obesity epidemic: adaptive, maladaptive, and neutral viewpoints
Speakman, J. R. (2013) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071811-150711 · Cited by 163 · see citing works
Legro, R. S., Kunselman, A. R., Demers, L., Wang, S. C., Bentley–Lewis, R., & Dunaif, A. E. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.5.8387 · Cited by 161 · see citing works
Mulders, A. G. M. G. J. (2004) · Human Reproduction · doi:10.1093/humrep/deh373 · Cited by 155 · see citing works
New insights into the genetics of polycystic ovary syndrome
Azziz, R. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.230 · Cited by 142 · see citing works
Self-citationSelection for complex traits leaves little or no classic signatures of selection
Kemper, K. E., Saxton, S. J., Bolormaa, S., Hayes, B. J., & Goddard, M. E. (2014) · BMC Genomics · doi:10.1186/1471-2164-15-246 · Cited by 134 · see citing works
Stein and Leventhal: 80 years on
Azziz, R., & Adashi, E. Y. (2015) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2015.12.013 · Cited by 130 · see citing works
Self-citationSchmidt, J., Brännström, M., Landin-Wilhelmsen, K., & Dahlgren, E. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-2959 · Cited by 113 · see citing works
Gurven, M., Kaplan, H., Winking, J., Eid Rodriguez, D., Vasunilashorn, S., Kim, J. K., Finch, C., & Crimmins, E. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006590 · Cited by 107 · see citing works
Blood lipids, infection, and inflammatory markers in the Tsimane of Bolivia
Vasunilashorn, S., Crimmins, E. M., Kim, J. K., Winking, J., Gurven, M., Kaplan, H., & Finch, C. E. (2010) · American Journal of Human Biology · doi:10.1002/ajhb.21074 · Cited by 95 · see citing works
Pregnancy outcomes in women with polycystic ovary syndrome undergoing in vitro fertilization
Sterling, L., Liu, J., Okun, N. B., Sakhuja, A., Sierra, S., & Greenblatt, E. M. (2015) · Fertility and Sterility · doi:10.1016/j.fertnstert.2015.11.019 · Cited by 89 · see citing works
Fagny, M., Patin, É., Enard, D., Barreiro, L. B., Quintana‐Murci, L., & Laval, G. (2014) · Molecular Biology and Evolution · doi:10.1093/molbev/msu118 · Cited by 74 · see citing works
The Polycystic Ovary Syndrome and recent human evolution
Corbett, S., & Morin-Papunen, L. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.01.001 · Cited by 68 · see citing works
Casarini, L., & Brigante, G. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-2703 · Cited by 65 · see citing works
DNA mismatch repair gene MSH6 implicated in determining age at natural menopause
Perry, J. R. B., Hsu, Y., Chasman, D. I., Johnson, A. D., Elks, C. E., Albrecht, E., Andrulis, I. L., Beesley, J., Berenson, G. S., Bergmann, S., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt620 · Cited by 65 · see citing works
Corbett, S. J., McMichael, A. J., & Prentice, A. M. (2009) · American Journal of Human Biology · doi:10.1002/ajhb.20937 · Cited by 64 · see citing works
Holte, J. (1998) · Journal of Endocrinological Investigation · doi:10.1007/bf03350784 · Cited by 52 · see citing works
Erratum: PCOS in 2015: New insights into the genetics of polycystic ovary syndrome
Azziz, R. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.9 · Cited by 50 · see citing works
Self-citationMagen, E., Borkow, G., Bentwich, Z., et al. (2005) · Medical Hypotheses · doi:10.1016/j.mehy.2004.09.028 · Cited by 40 · see citing works
Is polycystic ovary syndrome a sexual conflict? A review
Casarini, L., Simoni, M., & Brigante, G. (2016) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2016.01.011 · Cited by 28 · see citing works
Saxena, R., Bjonnes, A., Georgopoulos, N. A., Koika, V., Panidis, D., & Welt, C. K. (2015) · Human Reproduction · doi:10.1093/humrep/dev110 · Cited by 26 · see citing works
Gleicher, N., & Barad, D. H. (2006) · Reproductive BioMedicine Online · doi:10.1016/s1472-6483(10)61184-4 · Cited by 20 · see citing works
Commentary: Polycystic ovary syndrome: a transgenerational evolutionary adaptation
Shaw, L., & Elton, S. (2008) · BJOG: An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.2007.01453.x · Cited by 20 · see citing works
An evolutionary approach to explain the high frequency of the polycystic ovary syndrome (PCOS)
Eggers, S., Hashimoto, D. M., & Kirchengast, S. (2007) · Anthropologischer Anzeiger · doi:10.1127/anthranz/65/2007/169 · Cited by 13 · see citing works
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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 · see citing works
Azziz, R. (2018) · Obstetrics & Gynecology · doi:10.1097/aog.0000000000002698 · Cited by 573 · see citing works
Self-citationIbáñez, L., Oberfield, S. E., Witchel, S., Auchus, R. J., Chang, R. J., Codner, E., Dabadghao, P., Darendeliler, F., Elbarbary, N. S., Gambineri, A., et al. (2017) · Hormone Research in Paediatrics · doi:10.1159/000479371 · Cited by 463 · see citing works
The evolutionary biology of endometriosis
Dinsdale, N., Nepomnaschy, P., & Crespi, B. (2021) · Evolution, Medicine, and Public Health · doi:10.1093/emph/eoab008 · Cited by 53 · see citing works
Evolutionary origins of polycystic ovary syndrome: An environmental mismatch disorder
Charifson, M. A., & Trumble, B. C. (2019) · Evolution, Medicine, and Public Health · doi:10.1093/emph/eoz011 · Cited by 44 · see citing works
Is polycystic ovary syndrome a 20th Century phenomenon?
Rodgers, R. J., Suturina, L., Lizneva, D., Davies, M. J., Hummitzsch, K., Irving-Rodgers, H. F., & Robertson, S. A. (2019) · Medical Hypotheses · doi:10.1016/j.mehy.2019.01.019 · Cited by 34 · see citing works
Leung, K. L., Sanchita, S., Pham, C. T., Davis, B. A., Okhovat, M., Ding, X., Dumesic, P., Grogan, T. R., Williams, K. J., Morselli, M., et al. (2020) · Clinical Epigenetics · doi:10.1186/s13148-020-00970-x · Cited by 33 · see citing works
- Authors
- Fessler, D. M. T., Natterson-Horowitz, B., & Azziz, R.
- Affiliations
- University of California, Los Angeles (US)
- Augusta University (US)
- Corresponding author
- Azziz, Ricardo
- Venue
- Fertility and Sterility
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 106
- Issue
- 1
- Pages
- 42-47
- ISSN
- 0015-0282 (ISSN-L)
- OpenAlex
- W2395155508
- Cited by
- 44
- References
- 37
- Citations by year
- 2025: 5 · 2024: 4 · 2023: 6 · 2022: 1 · 2021: 4 · 2020: 7 · 2019: 4 · 2018: 11 · 2017: 2
- FWCI
- 0.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Fertility and Sterility (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Evolutionary Psychology and Human Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Keywords
- polycystic ovary syndrome, evolutionary origin, evolutionary paradox, reproductive fitness, ancestral populations, founder effect, genetic drift, sexually antagonistic selection, selection dynamics, metabolic function, immune system, parenting, reproductive longevity, disease prevalence
- MeSH terms
- Adaptation, Physiological, Female, Genetic Markers, Humans, Phenotype, Polycystic Ovary Syndrome, Reproduction, Risk Factors, Selection, Genetic, Genetic Variation, Evolution, Molecular, Genetic Predisposition to Disease, Genetic Drift, Reproductive Health, Hygiene Hypothesis
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