Scientific Statement on the Diagnostic Criteria, Epidemiology, Pathophysiology, and Molecular Genetics of Polycystic Ovary Syndrome

Dumesic, Daniel A.; Oberfield, Sharon E.; Stener-Victorin, Elisabet; Marshall, John C.; Laven, Joop S.; Legro, Richard S.

doi:10.1210/er.2015-1018

Cited by 1,020Ovarian function and disordersGenetic and Kidney Cyst DiseasesReproductive Biology and Fertility

Scientific Statement on the Diagnostic Criteria, Epidemiology, Pathophysiology, and Molecular Genetics of Polycystic Ovary Syndrome

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Dumesic, Daniel A., Oberfield, Sharon E., Stener-Victorin, Elisabet, Marshall, John C., Laven, Joop S., Legro, Richard S.·2015·Endocrine Reviews

DOI 10.1210/er.2015-1018PMC PMC4591526

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Abstract

Polycystic ovary syndrome (PCOS) is a heterogeneous and complex disorder that has both adverse reproductive and metabolic implications for affected women. However, there is generally poor understanding of its etiology. Varying expert-based diagnostic criteria utilize some combination of oligo-ovulation, hyperandrogenism, and the presence of polycystic ovaries. Criteria that require hyperandrogenism tend to identify a more severe reproductive and metabolic phenotype. The phenotype can vary by race and ethnicity, is difficult to define in the perimenarchal and perimenopausal period, and is exacerbated by obesity. The pathophysiology involves abnormal gonadotropin secretion from a reduced hypothalamic feedback response to circulating sex steroids, altered ovarian morphology and functional changes, and disordered insulin action in a variety of target tissues. PCOS clusters in families and both female and male relatives can show stigmata of the syndrome, including metabolic abnormalities. Genome-wide association studies have identified a number of candidate regions, although their role in contributing to PCOS is still largely unknown.

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The correlation between DHEAS levels and insulin resistance in women with PCOS is logical, as DHEAS levels decrease with medication that enhances insulin sensitivity.
“The correlation between DHEAS levels and IR in women with PCOS seems logical, as these levels decrease with medication that enhances insulin sensitivity [62].”
From Nutritional and herbal interventions for polycystic ovary syndrome (PCOS): a comprehensive review of dietary approaches, macronutrient impact, and herbal medicine in management (2025) · cites this paper as [62]
IR has been indicated as a key etiological component of PCOS.
“Although the causes of PCOS have not yet been fully defined, insulin resistance (IR) has been indicated as a key etiological component (6).”
From Effect of Diet on Insulin Resistance in Polycystic Ovary Syndrome (2020) · cites this paper as [6]
In contrast to total T, free T seems to be a better marker to determine hyperandrogenemia in women with PCOS, provided that accurate and high quality methodology is used for measured or calculated free T.
“In contrast to total T, free T seems to be a better marker to determine hyperandrogenemia in women with PCOS [187], provided that accurate and high quality methodology is used for measured or calculated free T [193, 194].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [194]

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The effect of obesity on polycystic ovary syndrome: a systematic review and meta‐analysis
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Troglitazone Improves Ovulation and Hirsutism in the Polycystic Ovary Syndrome: A Multicenter, Double Blind, Placebo-Controlled Trial1
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Menstrual cycle irregularity and risk for future cardiovascular disease
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Formation and early development of follicles in the polycystic ovary
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Granulosa Cell Production of Anti-Müllerian Hormone Is Increased in Polycystic Ovaries
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Accurate Assessment of β-Cell Function
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Theca: the forgotten cell of the ovarian follicle
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The follicular excess in polycystic ovaries, due to intra-ovarian hyperandrogenism, may be the main culprit for the follicular arrest
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Evidence for Association Between Polycystic Ovary Syndrome and Premature Carotid Atherosclerosis in Middle-Aged Women
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Precocious Pubarche, Hyperinsulinism, and Ovarian Hyperandrogenism in Girls: Relation to Reduced Fetal Growth
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Evaluation and Treatment of Hirsutism in Premenopausal Women: An Endocrine Society Clinical Practice Guideline
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Mortality of Women with Polycystic Ovary Syndrome at Long-term Follow-up
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A Sustained Increase in Plasma Free Fatty Acids Impairs Insulin Secretion in Nondiabetic Subjects Genetically Predisposed to Develop Type 2 Diabetes
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Polycystic Ovary Syndrome as a Form of FunctionalOvarian Hyperandrogenism Due to Dysregulation ofAndrogen Secretion*
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Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society
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Diagnosis of polycystic ovary syndrome (PCOS): revisiting the threshold values of follicle count on ultrasound and of the serum AMH level for the definition of polycystic ovaries
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A New Rat Model Exhibiting Both Ovarian and Metabolic Characteristics of Polycystic Ovary Syndrome
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Extra- and intra-ovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence
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Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations
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Premature Adrenarche - A Common Condition with Variable Presentation
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Polycystic Ovary Syndrome Is Associated With Endothelial Dysfunction
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Positive Relationship between Androgen and the Endocrine Disruptor, Bisphenol A, in Normal Women and Women with Ovarian Dysfunction
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Beta-cell dysfunction independent of obesity and glucose intolerance in the polycystic ovary syndrome
Dunaif, A. E., & Finegood, D. T. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.3.8772555 · Cited by 454 · see citing works
Adolescent Girls with Polycystic Ovary Syndrome Have an Increased Risk of the Metabolic Syndrome Associated with Increasing Androgen Levels Independent of Obesity and Insulin Resistance
Coviello, A. D., Legro, R. S., & Dunaif, A. E. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-1666 · Cited by 446 · see citing works
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PCOS according to the Rotterdam consensus criteria: change in prevalence among WHO‐II anovulation and association with metabolic factors
Broekmans, F. J., Knauff, E. A. H., Valkenburg, O., Laven, J. S. E., Eijkemans, M. J. C., & Fauser, B. C. J. M. (2006) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.2006.01008.x · Cited by 445 · see citing works
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Role of Hormones in Pilosebaceous Unit Development
Deplewski, D., & Rosenfield, R. L. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.4.0404 · Cited by 443 · see citing works
Does ethnicity influence the prevalence of adrenal hyperandrogenism and insulin resistance in polycystic ovary syndrome?
Carmina, E., Koyama, T., Chang, L., Stanczyk, F. Z., & Løbo, R. A. (1992) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(92)91779-a · Cited by 441 · see citing works
Pulse and Respiratory Grouping of Sympathetic Impulses in Human Muscle Nerves
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Quality of Life, Psychosocial Well-Being, and Sexual Satisfaction in Women with Polycystic Ovary Syndrome
Elsenbruch, S., Hahn, S., Kowalsky, D., Öffner, A. H., Schedlowski, M., Mann, K., & Janssen, O. E. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030562 · Cited by 437 · see citing works
Restored insulin sensitivity but persistently increased early insulin secretion after weight loss in obese women with polycystic ovary syndrome.
Holte, J., Bergh, T., Berne, C., Wide, L., & Lithell, H. (1995) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.80.9.7673399 · Cited by 435 · see citing works
Morphology and Morphogenesis of the Stein-Leventhal Ovary and of So-called “Hyperthecosis”
Hughesdon, P. E. (1982) · Obstetrical & Gynecological Survey · doi:10.1097/00006254-198202000-00001 · Cited by 429 · see citing works
Insulin secretory defects in polycystic ovary syndrome. Relationship to insulin sensitivity and family history of non-insulin-dependent diabetes mellitus.
Ehrmann, D. A., Sturis, J., Byrne, M. M., Karrison, T., Rosenfield, R. L., & Polonsky, K. S. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118064 · Cited by 426 · see citing works
Premature Adrenarche--Normal Variant or Forerunner of Adult Disease?
Ibáñez, L., DiMartino-Nardi, J., Potau, N., & Saenger, P. H. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.6.0416 · Cited by 414 · see citing works
Epidemiology and Adverse Cardiovascular Risk Profile of Diagnosed Polycystic Ovary Syndrome
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Polycystic ovary syndrome and endometrial carcinoma
Hardiman, P. J., Pillay, O., & Atiomo, W. (2003) · The Lancet · doi:10.1016/s0140-6736(03)13409-5 · Cited by 414 · see citing works
Maternal serum androgens in pregnant women with polycystic ovarian syndrome: possible implications in prenatal androgenization
Sir‐Petermann, T. (2002) · Human Reproduction · doi:10.1093/humrep/17.10.2573 · Cited by 412 · see citing works
Prevalence of polycystic ovary syndrome (PCOS) in first-degree relatives of patients with PCOS
Kahsar-Miller, M. D., Nixon, C., Boots, L. R., Go, R. C., & Azziz, R. (2001) · Fertility and Sterility · doi:10.1016/s0015-0282(00)01662-9 · Cited by 406 · see citing works
Polycystic ovary syndrome as a form of functional ovarian hyperandrogenism due to dysregulation of androgen secretion
Ehrmann, D. A. (1995) · Endocrine Reviews · doi:10.1210/er.16.3.322 · Cited by 403 · see citing works
Impact of Obesity on the Risk for Polycystic Ovary Syndrome
Yildiz, B. O., Knochenhauer, E. S., & Azziz, R. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-1834 · Cited by 401 · see citing works
Hyperfunction of the Hypothalamic-Pituitary Axis in Women with Polycystic Ovarian Disease: Indirect Evidence for Partial Gonadotroph Desensitization*
Waldstreicher, J., Santoro, N. F., Hall, J. E., Filicori, M., & Crowley, W. F. (1988) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-66-1-165 · Cited by 400 · see citing works
Prevalence and Predictors of Coronary Artery Calcification in Women with Polycystic Ovary Syndrome
Christian, R. C., Dumesic, D. A., Behrenbeck, T. R., Oberg, A. L., Sheedy, P. F., & Fitzpatrick, L. A. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030334 · Cited by 396 · see citing works
Self-citation
The Polycystic Ovary Syndrome Associated with Morbid Obesity May Resolve after Weight Loss Induced by Bariatric Surgery
Escobar-Morreale, H. F., Botella-Carretero, J. I., Álvarez‐Blasco, F., Sancho, J., & Millán, J. L. S. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-1490 · Cited by 389 · see citing works
Endocrine Disruptors and Polycystic Ovary Syndrome (PCOS): Elevated Serum Levels of Bisphenol A in Women with PCOS
Kandaraki, E., Chatzigeorgiou, A., Livadas, S., Palioura, E., Economou, F., Koutsilieris, M., Palimeri, S., Panidis, D., & Diamanti‐Kandarakis, E. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-1658 · Cited by 387 · see citing works
Assessment and management of polycystic ovary syndrome: Summary of an evidence-based guideline
Teede, H. J., Misso, M. L., Deeks, A. A., Moran, L. J., Stuckey, B. G. A., Wong, J. L. A., Norman, R. J., Costello, M. F., & Groups, O. B. O. T. G. D. (2011) · Medical Journal of Australia · doi:10.5694/mja11.10915 · Cited by 379 · see citing works
Troglitazone Improves Ovulation and Hirsutism in the Polycystic Ovary Syndrome: A Multicenter, Double Blind, Placebo-Controlled Trial
Azziz, R. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.86.4.1626 · Cited by 378 · see citing works
Anti-Mullerian Hormone and Inhibin B in the Definition of Ovarian Aging and the Menopause Transition
Sowers, M. F., Eyvazzadeh, A. D., McConnell, D. S., Yosef, M., Jannausch, M. L., Zhang, D., Harlow, S. D., & Randolph, J. F. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0567 · Cited by 376 · see citing works
Diet, Obesity and Hypertension: An Hypothesis Involving Insulin, the Sympathetic Nervous System, and Adaptive Thermogenesis
LANDSBERG, L. (1986) · QJM: An International Journal of Medicine · doi:10.1093/oxfordjournals.qjmed.a068066 · Cited by 373 · see citing works
Adipose Tissue Has Aberrant Morphology and Function in PCOS: Enlarged Adipocytes and Low Serum Adiponectin, but Not Circulating Sex Steroids, Are Strongly Associated with Insulin Resistance
Mannerås-Holm, L., Leonhardt, H., Kullberg, J., Jennische, E., Odén, A., Holm, G., Hellström, M., Lönn, L., Olivecrona, G., Stener-Victorin, E., et al. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-1290 · Cited by 369 · see citing works
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Polycystic Ovarian Syndrome: Evidence that Flutamide Restores Sensitivity of the Gonadotropin-Releasing Hormone Pulse Generator to Inhibition by Estradiol and Progesterone 1
Eagleson, C. A., Gingrich, M. B., Pastor, C. L., Arora, T. K., Solorzano, C. M. B., Evans, W. S., & Marshall, J. C. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.11.6992 · Cited by 368 · see citing works
Self-citation
KUMUDINI HOSPITAL
Habershon, R. (1975) · The Lancet · doi:10.1016/s0140-6736(75)93067-6 · Cited by 368 · see citing works
Ultrasound examination of polycystic ovaries: is it worth counting the follicles?
Jonard, S. (2003) · Human Reproduction · doi:10.1093/humrep/deg115 · Cited by 367 · see citing works
Overweight and obese anovulatory patients with polycystic ovaries: parallel improvements in anthropometric indices, ovarian physiology and fertility rate induced by diet
Crosignani, P. G. (2003) · Human Reproduction · doi:10.1093/humrep/deg367 · Cited by 359 · see citing works
Endometrial cancer and obesity: Epidemiology, biomarkers, prevention and survivorship
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Screening Women With Polycystic Ovary Syndrome for Metabolic Syndrome
Dokras, A., Bochner, M., Hollinrake, E., Markham, S. M., Voorhis, B. J. V., & Jagasia, D. H. (2005) · Obstetrics and Gynecology · doi:10.1097/01.aog.0000167408.30893.6b · Cited by 353 · see citing works
Prevalence and Characteristics of the Polycystic Ovary Syndrome in Overweight and Obese Women
Álvarez‐Blasco, F., Botella-Carretero, J. I., Millán, J. L. S., & Escobar-Morreale, H. F. (2006) · Archives of Internal Medicine · doi:10.1001/archinte.166.19.2081 · Cited by 348 · see citing works
Relative risk of conversion from normoglycaemia to impaired glucose tolerance or non-insulin dependent diabetes mellitus in polycystic ovarian syndrome
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Effect of central and peripheral body fat distribution on sympathetic and baroreflex function in obese normotensives
Grassi, G. M., Dell’Oro, R., Facchini, A., Trevano, F. Q., Bolla, G. B., & Mancia, G. (2004) · Journal of Hypertension · doi:10.1097/00004872-200412000-00019 · Cited by 339 · see citing works
The diagnosis of polycystic ovary syndrome in adolescents
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Defects in insulin receptor signaling in vivo in the polycystic ovary syndrome (PCOS)
Dunaif, A., Wu, X., Lee, A., & Diamanti-Kandarakis, E. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.281.2.e392 · Cited by 337 · see citing works
Cellular mechanisms of insulin resistance in polycystic ovarian syndrome
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Epithelial Ovarian Cancer Risk Among Women With Polycystic Ovary Syndrome
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The Frequency of Gonadotropin-Releasing-Hormone Stimulation Differentially Regulates Gonadotropin Subunit Messenger Ribonucleic Acid Expression*
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The role of lifestyle modification in polycystic ovary syndrome
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Early Menarche, a Risk Factor for Breast Cancer, Indicates Early Onset of Ovulatory Cycles*
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Detection of Functional Ovarian Hyperandrogenism in Women with Androgen Excess
Ehrmann, D. A., Rosenfield, R. L., Barnes, R. B., Brigell, D. F., & Sheikh, Z. (1992) · New England Journal of Medicine · doi:10.1056/nejm199207163270304 · Cited by 322 · see citing works
Anti-Müllerian hormone levels reflect severity of PCOS but are negatively influenced by obesity: relationship with increased luteinizing hormone levels
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Clinical manifestations and insulin resistance (IR) in polycystic ovary syndrome (PCOS) among South Asians and Caucasians: is there a difference?
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Rodent Models for Human Polycystic Ovary Syndrome1
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Adverse Lipid and Coronary Heart Disease Risk Profiles in Young Women with Polycystic Ovary Syndrome: Results of a Case-Control Study
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Changes in Glucose Tolerance over Time in Women with Polycystic Ovary Syndrome: A Controlled Study
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Molecular Abnormalities in Oocytes from Women with Polycystic Ovary Syndrome Revealed by Microarray Analysis
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Ovarian hyperandrogynism as a result of congenital adrenal virilizing disorders: evidence for perinatal masculinization of neuroendocrine function in women
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Evidence for a primary abnormality of thecal cell steroidogenesis in the polycystic ovary syndrome
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The origins and sequelae of abnormal neuroendocrine function in polycystic ovary syndrome
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Polycystic ovarian syndrome: Pathophysiology, molecular aspects and clinical implications
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Enhanced early insulin response to glucose in relation to insulin resistance in women with polycystic ovary syndrome and normal glucose tolerance
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miRNA-93 Inhibits GLUT4 and Is Overexpressed in Adipose Tissue of Polycystic Ovary Syndrome Patients and Women With Insulin Resistance
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Polycystic Ovarian Syndrome: Evidence that Flutamide Restores Sensitivity of the Gonadotropin-Releasing Hormone Pulse Generator to Inhibition by Estradiol and Progesterone
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Evidence for a single gene effect causing polycystic ovaries and male pattern baldness
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Authors: Dumesic, D. A., Oberfield, S. E., Stener-Victorin, E., Marshall, J. C., Laven, J. S., & Legro, R. S.
Affiliations: University of California, Los Angeles (US)
Morgan Stanley Children's Hospital (US)
Department of Physiology (E.S.-V.), Karolinska Institutet, 171 77 Stockholm, Sweden;
University of Virginia Health System (US)
Erasmus MC (NL)
Pennsylvania State University (US)
ORCID: Dumesic, Daniel A.
Oberfield, Sharon E.
Marshall, John C.
Laven, Joop S.
Legro, Richard S.
Venue: Endocrine Reviews
Publisher: The Endocrine Society
Published: 2015-10-01
Volume: 36
Issue: 5
Pages: 487-525
ISSN: 0163-769X (ISSN-L)
1945-7189
DOI: 10.1210/er.2015-1018
PMC: PMC4591526
OpenAlex: W2113329249
Cited by: 1,020
References: 472
Citations by year: 2026: 89 · 2025: 108 · 2024: 129 · 2023: 126 · 2022: 131 · 2021: 124 · 2020: 91 · 2019: 80 · 2018: 58 · 2017: 51 · 2016: 28 · 2015: 2 · 2012: 1
FWCI: 7.03
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Endocrine Reviews (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
Funders: University of Pennsylvania
Pennsylvania State University
Novo Nordisk Fonden (NNF15OC0015902)
National Institutes of Health (28934, U54-HD28-934)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD071836, U54HD028934, U54HD034449, U10HD038992, P50HD028934, 2 U10 HD 38992, R01HD056510, U54-HD-28934)
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 › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
Keywords: polycystic ovary syndrome, diagnostic criteria, epidemiology, pathophysiology, molecular genetics, hyperandrogenism, oligoovulation, insulin resistance, gonadotropin secretion, hypothalamic-pituitary feedback, obesity, reproductive phenotypes, metabolic phenotypes, familial aggregation, genome-wide association study, sex steroids
MeSH terms: Diagnosis, Differential, Female, Humans, Polycystic Ovary Syndrome

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