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Epidemiology and pathogenesis of the polycystic ovary syndrome in adults

Author
Ricardo Azziz, MD, MBA, MPH
Section Editor
William F Crowley, Jr, MD
Deputy Editor
Kathryn A Martin, MD

INTRODUCTION

Polycystic ovary syndrome (PCOS), a heterogeneous complex genetic trait of unclear etiology, is an important cause of ovulatory and menstrual irregularity, subfertility and infertility, clinically evident hyperandrogenism, and metabolic dysfunction in women. When fully expressed, the manifestations include ovulatory dysfunction, androgen excess, and polycystic ovaries. It is recognized as one of the most common endocrine/metabolic disorders of women. This syndrome was first described by Stein and Leventhal in 1935 [1], although the presence of sclerocystic ovaries had been recognized for at least 90 years prior to their report.

The definition, pathogenesis, and etiology of PCOS will be reviewed here. The clinical manifestations, diagnosis, and treatment of PCOS are discussed separately. (See "Clinical manifestations of polycystic ovary syndrome in adults" and "Diagnosis of polycystic ovary syndrome in adults" and "Treatment of polycystic ovary syndrome in adults".)

DEFINITION

The principal features of polycystic ovary syndrome (PCOS) include androgen excess, ovulatory dysfunction, and/or polycystic ovaries [2]. There are several proposed diagnostic criteria for PCOS that are reviewed in detail separately (see "Diagnosis of polycystic ovary syndrome in adults", section on 'Diagnosis'). Of note, the National Institutes of Health (NIH) Evidence-based Methodology Workshop Panel on Polycystic Ovary Syndrome in 2012 suggested the following recommendations [3]: (1) renaming the disorder to more adequately reflect the complex metabolic, hypothalamic, pituitary, ovarian, and adrenal interactions that characterize the syndrome (and their reproductive implications, although no specific name was recommended); and (2) maintaining the broad, inclusionary diagnostic criteria of Rotterdam (which includes the “classic NIH” and the Androgen Excess and PCOS Society criteria), while specifically identifying each of the subphenotypes in research and clinical initiatives. (See "Diagnosis of polycystic ovary syndrome in adults".)

EPIDEMIOLOGY

Polycystic ovary syndrome (PCOS) is recognized as one of the most common endocrine/metabolic disorders in women. Its prevalence depends in part upon the diagnostic criteria used to define the disorder [4]. As an example, in a report of 827 women with World Health Organization (WHO) class II oligoovulation (euestrogenic normogonadotropic ovulatory dysfunction), 456 (55 percent) were classified as having PCOS by the National Institutes of Health (NIH) 1990 criteria (irregular menses, biochemical and/or clinical hyperandrogenism, and other causes of hyperandrogenism excluded). In contrast, 754 (91 percent) women were considered to have PCOS using the broader Rotterdam 2003 criteria (which requires two out of three of the following: oligo- and/or anovulation, clinical and/or biochemical signs of hyperandrogenism, and polycystic ovaries [by ultrasound]) [5]. Other causes of hyperandrogenism must also be excluded. (See "Diagnosis of polycystic ovary syndrome in adults", section on 'Other proposed criteria'.)

General population — To date, the prevalence of PCOS has been determined primarily using the NIH 1990 criteria. Fairly uniform prevalences of PCOS in unselected women, ranging from 6 to 10 percent, have been reported in many populations around the globe [4,6-9], with few exceptions.

            

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References
Top
  1. Stein, IF, Leventhal, NL. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol 1935; 29:181.
  2. Norman RJ, Dewailly D, Legro RS, Hickey TE. Polycystic ovary syndrome. Lancet 2007; 370:685.
  3. National Institutes of Health. Evidence-based methodology workshop on polycystic ovary syndrome, December 2012: Final report. http://prevention.nih.gov/workshops/2012/pcos/docs/PCOS_Final_Statement.pdf (Accessed on April 29, 2013).
  4. March WA, Moore VM, Willson KJ, et al. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod 2010; 25:544.
  5. Broekmans FJ, Knauff EA, Valkenburg O, et al. PCOS according to the Rotterdam consensus criteria: Change in prevalence among WHO-II anovulation and association with metabolic factors. BJOG 2006; 113:1210.
  6. Diamanti-Kandarakis E, Kouli CR, Bergiele AT, et al. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab 1999; 84:4006.
  7. Asunción M, Calvo RM, San Millán JL, et al. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab 2000; 85:2434.
  8. Michelmore KF, Balen AH, Dunger DB, Vessey MP. Polycystic ovaries and associated clinical and biochemical features in young women. Clin Endocrinol (Oxf) 1999; 51:779.
  9. Tehrani FR, Simbar M, Tohidi M, et al. The prevalence of polycystic ovary syndrome in a community sample of Iranian population: Iranian PCOS prevalence study. Reprod Biol Endocrinol 2011; 9:39.
  10. Kousta E, White DM, Cela E, et al. The prevalence of polycystic ovaries in women with infertility. Hum Reprod 1999; 14:2720.
  11. Hull MG. Epidemiology of infertility and polycystic ovarian disease: endocrinological and demographic studies. Gynecol Endocrinol 1987; 1:235.
  12. Allen SE, Potter HD, Azziz R. Prevalence of hyperandrogenemia among nonhirsute oligo-ovulatory women. Fertil Steril 1997; 67:569.
  13. Hartz AJ, Barboriak PN, Wong A, et al. The association of obesity with infertility and related menstural abnormalities in women. Int J Obes 1979; 3:57.
  14. Korhonen S, Hippeläinen M, Niskanen L, et al. Relationship of the metabolic syndrome and obesity to polycystic ovary syndrome: a controlled, population-based study. Am J Obstet Gynecol 2001; 184:289.
  15. Alvarez-Blasco F, Botella-Carretero JI, San Millán JL, Escobar-Morreale HF. Prevalence and characteristics of the polycystic ovary syndrome in overweight and obese women. Arch Intern Med 2006; 166:2081.
  16. Yildiz BO, Knochenhauer ES, Azziz R. Impact of obesity on the risk for polycystic ovary syndrome. J Clin Endocrinol Metab 2008; 93:162.
  17. Escobar-Morreale HF, Roldán B, Barrio R, et al. High prevalence of the polycystic ovary syndrome and hirsutism in women with type 1 diabetes mellitus. J Clin Endocrinol Metab 2000; 85:4182.
  18. Codner E, Soto N, Lopez P, et al. Diagnostic criteria for polycystic ovary syndrome and ovarian morphology in women with type 1 diabetes mellitus. J Clin Endocrinol Metab 2006; 91:2250.
  19. Conn JJ, Jacobs HS, Conway GS. The prevalence of polycystic ovaries in women with type 2 diabetes mellitus. Clin Endocrinol (Oxf) 2000; 52:81.
  20. Peppard HR, Marfori J, Iuorno MJ, Nestler JE. Prevalence of polycystic ovary syndrome among premenopausal women with type 2 diabetes. Diabetes Care 2001; 24:1050.
  21. Holte J, Gennarelli G, Wide L, et al. High prevalence of polycystic ovaries and associated clinical, endocrine, and metabolic features in women with previous gestational diabetes mellitus. J Clin Endocrinol Metab 1998; 83:1143.
  22. Anttila L, Karjala K, Penttilä RA, et al. Polycystic ovaries in women with gestational diabetes. Obstet Gynecol 1998; 92:13.
  23. Ibáñez L, Dimartino-Nardi J, Potau N, Saenger P. Premature adrenarche--normal variant or forerunner of adult disease? Endocr Rev 2000; 21:671.
  24. Rosenfield RL. Clinical review: Identifying children at risk for polycystic ovary syndrome. J Clin Endocrinol Metab 2007; 92:787.
  25. Legro RS, Driscoll D, Strauss JF 3rd, et al. Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome. Proc Natl Acad Sci U S A 1998; 95:14956.
  26. Kahsar-Miller MD, Nixon C, Boots LR, et al. Prevalence of polycystic ovary syndrome (PCOS) in first-degree relatives of patients with PCOS. Fertil Steril 2001; 75:53.
  27. Goodarzi MO, Quiñones MJ, Azziz R, et al. Polycystic ovary syndrome in Mexican-Americans: prevalence and association with the severity of insulin resistance. Fertil Steril 2005; 84:766.
  28. Kauffman RP, Baker VM, Dimarino P, et al. Polycystic ovarian syndrome and insulin resistance in white and Mexican American women: a comparison of two distinct populations. Am J Obstet Gynecol 2002; 187:1362.
  29. Bilo L, Meo R, Valentino R, et al. Characterization of reproductive endocrine disorders in women with epilepsy. J Clin Endocrinol Metab 2001; 86:2950.
  30. Joffe H, Taylor AE, Hall JE. Polycystic ovarian syndrome--relationship to epilepsy and antiepileptic drug therapy. J Clin Endocrinol Metab 2001; 86:2946.
  31. Isojärvi JI, Laatikainen TJ, Pakarinen AJ, et al. Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy. N Engl J Med 1993; 329:1383.
  32. Mikkonen K, Vainionpää LK, Pakarinen AJ, et al. Long-term reproductive endocrine health in young women with epilepsy during puberty. Neurology 2004; 62:445.
  33. Joffe H, Cohen LS, Suppes T, et al. Valproate is associated with new-onset oligoamenorrhea with hyperandrogenism in women with bipolar disorder. Biol Psychiatry 2006; 59:1078.
  34. Joffe H, Cohen LS, Suppes T, et al. Longitudinal follow-up of reproductive and metabolic features of valproate-associated polycystic ovarian syndrome features: A preliminary report. Biol Psychiatry 2006; 60:1378.
  35. Nelson-DeGrave VL, Wickenheisser JK, Cockrell JE, et al. Valproate potentiates androgen biosynthesis in human ovarian theca cells. Endocrinology 2004; 145:799.
  36. Forgue, E, Massabuau, G. L'ovaire a petits kystes (cont.). Revue de Gynécologie et de Chirurgie Abdminale 1910; 14:209.
  37. Hughesdon PE. Morphology and morphogenesis of the Stein-Leventhal ovary and of so-called "hyperthecosis". Obstet Gynecol Surv 1982; 37:59.
  38. JONES GE, HOWARD JE, LANGFORD H. The use of cortisone in follicular phase disturbances. Fertil Steril 1953; 4:49.
  39. GREENBLATT RB. Cortisone in treatment of the hirsute woman. Am J Obstet Gynecol 1953; 66:700.
  40. Kumar A, Woods KS, Bartolucci AA, Azziz R. Prevalence of adrenal androgen excess in patients with the polycystic ovary syndrome (PCOS). Clin Endocrinol (Oxf) 2005; 62:644.
  41. Vink JM, Sadrzadeh S, Lambalk CB, Boomsma DI. Heritability of polycystic ovary syndrome in a Dutch twin-family study. J Clin Endocrinol Metab 2006; 91:2100.
  42. Chen ZJ, Zhao H, He L, et al. Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Nat Genet 2011; 43:55.
  43. Simonis-Bik AM, Nijpels G, van Haeften TW, et al. Gene variants in the novel type 2 diabetes loci CDC123/CAMK1D, THADA, ADAMTS9, BCL11A, and MTNR1B affect different aspects of pancreatic beta-cell function. Diabetes 2010; 59:293.
  44. Goodarzi MO, Jones MR, Li X, et al. Replication of association of DENND1A and THADA variants with polycystic ovary syndrome in European cohorts. J Med Genet 2012; 49:90.
  45. Azziz R, Dumesic DA, Goodarzi MO. Polycystic ovary syndrome: an ancient disorder? Fertil Steril 2011; 95:1544.
  46. McAllister JM, Modi B, Miller BA, et al. Overexpression of a DENND1A isoform produces a polycystic ovary syndrome theca phenotype. Proc Natl Acad Sci U S A 2014; 111:E1519.
  47. Geist, SH. Reaction of the mature human ovary to antuitrin-S. Am J Obstet Gynecol 1933; 26:588.
  48. KEETTEL WC, BRADBURY JT, STODDARD FJ. Observations on the polycystic ovary syndrome. Am J Obstet Gynecol 1957; 73:954.
  49. McARTHUR JW, INGERSOLL FM, WORCESTER J. The urinary excretion of interstitial-cell and follicle-stimulating hormone activity by women with diseases of the reproductive system. J Clin Endocrinol Metab 1958; 18:1202.
  50. INGERSOLL FM, McARTHUR JW. Longitudinal studies of gonadotropin excretion in the Stein-Leventhal syndrome. Am J Obstet Gynecol 1959; 77:795.
  51. TAYMOR ML, BARNARD R. Luteinizing hormone excretion in the polycystic ovary syndrome. Fertil Steril 1962; 13:501.
  52. Yen SS, Vela P, Rankin J. Inappropriate secretion of follicle-stimulating hormone and luteinizing hormone in polycystic ovarian disease. J Clin Endocrinol Metab 1970; 30:435.
  53. Rebar R, Judd HL, Yen SS, et al. Characterization of the inappropriate gonadotropin secretion in polycystic ovary syndrome. J Clin Invest 1976; 57:1320.
  54. Balen AH. Hypersecretion of luteinizing hormone and the polycystic ovary syndrome. Hum Reprod 1993; 8 Suppl 2:123.
  55. Waldstreicher J, Santoro NF, Hall JE, et al. Hyperfunction of the hypothalamic-pituitary axis in women with polycystic ovarian disease: indirect evidence for partial gonadotroph desensitization. J Clin Endocrinol Metab 1988; 66:165.
  56. Taylor AE, McCourt B, Martin KA, et al. Determinants of abnormal gonadotropin secretion in clinically defined women with polycystic ovary syndrome. J Clin Endocrinol Metab 1997; 82:2248.
  57. Jakimiuk AJ, Weitsman SR, Navab A, Magoffin DA. Luteinizing hormone receptor, steroidogenesis acute regulatory protein, and steroidogenic enzyme messenger ribonucleic acids are overexpressed in thecal and granulosa cells from polycystic ovaries. J Clin Endocrinol Metab 2001; 86:1318.
  58. Nilsson C, Jiang M, Pettersson K, et al. Determination of a common genetic variant of luteinizing hormone using DNA hybridization and immunoassays. Clin Endocrinol (Oxf) 1998; 49:369.
  59. Adams JM, Taylor AE, Crowley WF Jr, Hall JE. Polycystic ovarian morphology with regular ovulatory cycles: insights into the pathophysiology of polycystic ovarian syndrome. J Clin Endocrinol Metab 2004; 89:4343.
  60. Burghen GA, Givens JR, Kitabchi AE. Correlation of hyperandrogenism with hyperinsulinism in polycystic ovarian disease. J Clin Endocrinol Metab 1980; 50:113.
  61. Carmina E, Koyama T, Chang L, et al. Does ethnicity influence the prevalence of adrenal hyperandrogenism and insulin resistance in polycystic ovary syndrome? Am J Obstet Gynecol 1992; 167:1807.
  62. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997; 18:774.
  63. Legro RS, Finegood D, Dunaif A. A fasting glucose to insulin ratio is a useful measure of insulin sensitivity in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1998; 83:2694.
  64. DeUgarte CM, Bartolucci AA, Azziz R. Prevalence of insulin resistance in the polycystic ovary syndrome using the homeostasis model assessment. Fertil Steril 2005; 83:1454.
  65. Velazquez EM, Mendoza S, Hamer T, et al. Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metabolism 1994; 43:647.
  66. Nestler JE, Jakubowicz DJ, Evans WS, Pasquali R. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Engl J Med 1998; 338:1876.
  67. Azziz R, Ehrmann D, Legro RS, et al. Troglitazone improves ovulation and hirsutism in the polycystic ovary syndrome: a multicenter, double blind, placebo-controlled trial. J Clin Endocrinol Metab 2001; 86:1626.
  68. Lord JM, Flight IH, Norman RJ. Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, D-chiro-inositol) for polycystic ovary syndrome. Cochrane Database Syst Rev 2003; :CD003053.
  69. Barbieri RL, Makris A, Ryan KJ. Insulin stimulates androgen accumulation in incubations of human ovarian stroma and theca. Obstet Gynecol 1984; 64:73S.
  70. Nestler JE, Jakubowicz DJ, de Vargas AF, et al. Insulin stimulates testosterone biosynthesis by human thecal cells from women with polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system. J Clin Endocrinol Metab 1998; 83:2001.
  71. Plymate SR, Matej LA, Jones RE, Friedl KE. Inhibition of sex hormone-binding globulin production in the human hepatoma (Hep G2) cell line by insulin and prolactin. J Clin Endocrinol Metab 1988; 67:460.
  72. Nestler JE, Powers LP, Matt DW, et al. A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome. J Clin Endocrinol Metab 1991; 72:83.
  73. Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev 2012; 33:981.
  74. Chen YH, Heneidi S, Lee JM, et al. miRNA-93 inhibits GLUT4 and is overexpressed in adipose tissue of polycystic ovary syndrome patients and women with insulin resistance. Diabetes 2013; 62:2278.
  75. Legro RS, Kunselman AR, Dodson WC, Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab 1999; 84:165.
  76. Ehrmann DA, Liljenquist DR, Kasza K, et al. Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2006; 91:48.
  77. Dokras A, Jagasia DH, Maifeld M, et al. Obesity and insulin resistance but not hyperandrogenism mediates vascular dysfunction in women with polycystic ovary syndrome. Fertil Steril 2006; 86:1702.
  78. Barber TM, McCarthy MI, Wass JA, Franks S. Obesity and polycystic ovary syndrome. Clin Endocrinol (Oxf) 2006; 65:137.
  79. Boomsma CM, Eijkemans MJ, Hughes EG, et al. A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome. Hum Reprod Update 2006; 12:673.
  80. Azziz R, Sanchez LA, Knochenhauer ES, et al. Androgen excess in women: experience with over 1000 consecutive patients. J Clin Endocrinol Metab 2004; 89:453.
  81. Hedley AA, Ogden CL, Johnson CL, et al. Prevalence of overweight and obesity among US children, adolescents, and adults, 1999-2002. JAMA 2004; 291:2847.
  82. Carmina E, Rosato F, Jannì A, et al. Extensive clinical experience: relative prevalence of different androgen excess disorders in 950 women referred because of clinical hyperandrogenism. J Clin Endocrinol Metab 2006; 91:2.
  83. Azziz R, Woods KS, Reyna R, et al. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab 2004; 89:2745.
  84. Ezeh U, Yildiz BO, Azziz R. Referral bias in defining the phenotype and prevalence of obesity in polycystic ovary syndrome. J Clin Endocrinol Metab 2013; 98:E1088.
  85. Carmina E, Legro RS, Stamets K, et al. Difference in body weight between American and Italian women with polycystic ovary syndrome: influence of the diet. Hum Reprod 2003; 18:2289.
  86. Kandaraki E, Chatzigeorgiou A, Livadas S, et al. Endocrine disruptors and polycystic ovary syndrome (PCOS): elevated serum levels of bisphenol A in women with PCOS. J Clin Endocrinol Metab 2011; 96:E480.