Epidemiology, diagnosis, and management of polycystic ovary syndrome

Susan M Sirmans, Kristen A Pate, Susan M Sirmans, Kristen A Pate

Abstract

Polycystic ovary syndrome (PCOS) is a common heterogeneous endocrine disorder characterized by irregular menses, hyperandrogenism, and polycystic ovaries. The prevalence of PCOS varies depending on which criteria are used to make the diagnosis, but is as high as 15%-20% when the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine criteria are used. Clinical manifestations include oligomenorrhea or amenorrhea, hirsutism, and frequently infertility. Risk factors for PCOS in adults includes type 1 diabetes, type 2 diabetes, and gestational diabetes. Insulin resistance affects 50%-70% of women with PCOS leading to a number of comorbidities including metabolic syndrome, hypertension, dyslipidemia, glucose intolerance, and diabetes. Studies show that women with PCOS are more likely to have increased coronary artery calcium scores and increased carotid intima-media thickness. Mental health disorders including depression, anxiety, bipolar disorder and binge eating disorder also occur more frequently in women with PCOS. Weight loss improves menstrual irregularities, symptoms of androgen excess, and infertility. Management of clinical manifestations of PCOS includes oral contraceptives for menstrual irregularities and hirsutism. Spironolactone and finasteride are used to treat symptoms of androgen excess. Treatment options for infertility include clomiphene, laparoscopic ovarian drilling, gonadotropins, and assisted reproductive technology. Recent data suggest that letrozole and metformin may play an important role in ovulation induction. Proper diagnosis and management of PCOS is essential to address patient concerns but also to prevent future metabolic, endocrine, psychiatric, and cardiovascular complications.

Keywords: comorbidities; diagnosis; epidemiology; hyperandrogenism; management; polycystic ovary syndrome; women’s health.

References

    1. Stein IF, Leventhal ML. Amenorrhea associated with bilateral polycystic ovaries. Am J Obstet Gynecol. 1935;29:181–191.
    1. Farquhar C. Introduction and history of polycystic ovary syndrome. In: Kovacs G, Norman R, editors. Polycystic Ovary Syndrome. 2nd ed. Cambridge, UK: Cambridge University Press; 2007. pp. 4–24.
    1. Balen A, Conway G, Kaltsas G. Polycystic ovary syndrome: the spectrum of the disorder in 1741 patients. Hum Reprod. 1995;10:2107–2111.
    1. Hart R. Definitions, prevalence and symptoms of polycystic ovaries and the polycystic ovary syndrome. In: Allahbadia GN, Agrawal R, editors. Polycystic Ovary Syndrome. Kent, UK: Anshan, Ltd; 2007. pp. 15–26.
    1. Azziz R, Sanchez L, Knochenhauer ES, et al. Androgen excess in women: experience with over 1000 consecutive patients. J Clin Endocrinol Metab. 2004;89(2):453–462.
    1. Fauser B, Tarlatzis B, Rebar R, et al. Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril. 2012;97(1):28–38. e25.
    1. Ferriman D, Gallwey J. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab. 1961;21:1440–1447.
    1. Unluhizarci K, Kaltsas G, Kelestimur F. Non polycystic ovary syndrome-related endocrine disorders associated with hirsutism. Eur J Clin Invest. 2012;42(1):86–94.
    1. Adams J, Polson D, Franks S. Prevalence of polycystic ovaries in women with anovulation and idiopathic hirsutism. Br Med J (Clin Res Ed) 1986;293(6543):355–359.
    1. Souter I, Sanchez L, Perez M, Bartolucci A, Azziz R. The prevalence of androgen excess among patients with minimal unwanted hair growth. Am J Obstet Gynecol. 2004;191:1914–1920.
    1. Wijeyaratne CN, Balen AH, Barth JH, Belchetz PE. Clinical manifestations and insulin resistance (IR) in polycystic ovary syndrome (PCOS) among south Asians and Caucasians: is there a difference? Clin Endocrinol (Oxf) 2002;57:343–350.
    1. Lowenstein E. Diagnosis and management of the dermatologic manifestations of the polycystic ovary syndrome. Dermatol Ther. 2006;19(4):210–223.
    1. Eden J. The polycystic ovary syndrome presenting as resistant acne successfully treated with cyproterone acetate. Med J Aust. 1991;155(10):677–680.
    1. Teede H, Deeks A, Moran L. Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Med. 2010;8:41.
    1. Brassard M, AinMelk Y, Baillargeon JP. Basic infertility including polycystic ovary syndrome. Med Clin North Am. 2008;92:1163–1192.
    1. Glueck C, Phillips H, Cameron D, Sieve-Smith L, Wang P. Continuing metformin throughout pregnancy in women with polycystic ovary syndrome appears to safely reduce first-trimester spontaneous abortion: a pilot study. Fertil Steril. 2001;75(1):46–52.
    1. Jakubowicz DJ, Iuorno MJ, Jakubowicz S, Roberts K, Nestler JE. Effects of metformin on early pregnancy loss in the polycystic ovary syndrome. J Clin Endocrinol Metab. 2002;87(2):524–529.
    1. Zawadski JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome. In: Givens JHF, Merriman G, editors. The Polycystic Ovary Syndrome. Cambridge, MA: Blackwell Scientific; 1992. pp. 377–384.
    1. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81:19–25.
    1. Azziz R, Carmina E, DeWailly D, et al. Position statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab. 2006;91:4237–4245.
    1. Lujan ME, Jarrett BY, Brooks ED, et al. Updated ultrasound criteria for polycystic ovary syndrome: reliable thresholds for elevated follicle population and ovarian volume. Hum Reprod. 2013;28(5):1361–1368.
    1. Dewailly D, Gronier H, Poncelet E, et al. 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. Hum Reprod. 2011;26(11):3123–3129.
    1. Allemand MC, Tummon IS, Phy JL, Foong SC, Dumesic DA, Session DR. Diagnosis of polycystic ovaries by three-dimensional transvaginal ultrasound. Fertil Steril. 2006;85(1):214–219.
    1. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004;89:2745–2749.
    1. 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;84:4006–4011.
    1. Knochenhauer ES, Key TJ, Kahsar-Miller M, Waggoner W, Boots LR, Azziz R. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. J Clin Endocrinol Metab. 1998;83:3078–3082.
    1. Michelmore KF, Balen AH, Dunger DB, Vessey MP. Polycystic ovaries and associated clinical and biochemical features in young women. Clin Endocrinol (Oxf) 1999;51:779–786.
    1. Asuncion M, Calvo RM, San Millan JL, Sancho J, Avila S, Escobar-Morreale HF. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab. 2000;85:2434–2438.
    1. March WA, Moore VM, Willson KJ, Phillips DI, Norman RJ, Davies MJ. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod. 2010;25(2):544–551.
    1. Mehrabian F, Khani B, Kelishadi R, Ghanbari E. The prevalence of polycystic ovary syndrome in Iranian women based on different diagnostic criteria. Endokrynol Pol. 2011;62(3):238–242.
    1. Tehrani FR, Simbar M, Tohidi M, Hoseinpanah F, Azizi F. The prevalence of polycystic ovary syndrome in a community sample of Iranian population: Iranian PCOS prevalence study. Reprod Biol Endocrinol. 2011;9:39.
    1. Yildiz BO, Bozdag G, Yapici Z, Esinler I, Yarali H. Prevalence, phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria. Hum Reprod. 2012;27(10):3067–3073.
    1. Franks S, Gharani N, Waterworth D, et al. The genetic basis of polycystic ovary syndrome. Hum Reprod. 1997;12:2641–2648.
    1. Legro RS, Driscoll D, Straus III JF, Fox J, Dunaif A. Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome. Proc Natl Acad Sci U S A. 1998;95:14956–14960.
    1. Amato P, Simpson JL. The genetics of polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol. 2004;18(5):707–718.
    1. Crosignani PG, Nicolosi AE. Polycystic ovarian disease: heritability and heterogeneity. Hum Reprod Update. 2001;7(1):3–7.
    1. 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(6):2100–2104.
    1. Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol. 2011;7:219–231.
    1. 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;43:55–59.
    1. Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: An update on mechanism and implication. Endocrine Reviews. 2012;33(6):981–1030.
    1. Isikoglu M, Berkkanoglu M, Cemal H, Ozgur K. Polycystic ovary syndrome: What is the role of obesity? In: Allahbadia GN, Agrawal R, editors. Polycystic Ovary Syndrome. Kent, UK: Anshan, Ltd; 2007. pp. 157–163.
    1. Moran LJ, Hutchison SK, Norman RJ, Teede HJ. Lifestyle changes in women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2011;(7):CD007506.
    1. Alvarez-Blasco F, Botella-Carretero JI, San Millan JL, Escobar-Morreale H. Prevalence and characteristics of the polycystic ovary syndrome in overweight and obese women. Arch Intern Med. 2006;166:2081–2086.
    1. Yildiz B, Knochenhauer ES, Azziz R. Impact of obesity on the risk for polycystic ovary syndrome. J Clin Endocrinol Metab. 2008;93(1):162–168.
    1. Herzog AG. Menstrual disorders in women with epilepsy. Neurology. 2006;66(6 Suppl 3):S23–S28.
    1. Bilo L, Meo R, Valentino R, Di Carlo C, Striano S, Nappi C. Characterization of reproductive endocrine disorders in women with epilepsy. J Clin Endocrinol Metab. 2001;86:2950–2956.
    1. Betts T, Yarrow H, Dutton N, Greenhill L, Rolfe T. A study of anticonvulsant medication on ovarian function in a group of women with epilepsy who have only ever taken one anticonvulsant compared with a group of women without epilepsy. Seizure. 2003;12:323–329.
    1. Isojarvi JI, Laatikainen TJ, Pakarinen AJ, Juntenen KT, Myllya VV. Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy. N Engl J Med. 1993;329:1383–1388.
    1. Isojarvi JI, Rattya J, Myllyla W, et al. Valproate, lamotrigine, and insulin-mediated risks in women with epilepsy. Ann Neurol. 1998;43(4):446–451.
    1. Escobar-Morreale HF, Roldan 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(11):4182–4187.
    1. 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(6):2250–2256.
    1. Conn JJ, Jacobs HS, Conway GS. The prevalence of polycystic ovaries in women with type 2 diabetes mellitus. Clin Endocrinol (Oxf) 2000;52(1):81–86.
    1. Peppard HR, Marfori J, Iuorno MJ, Nestler JE. Prevalence of polycystic ovary syndrome among premenopausal women with type 2 diabetes. Diabetes Care. 2001;24:1050–1052.
    1. Kashanian M, Fazy Z, Pirak A. Evaluation of the relationship between gestational diabetes and a history of polycystic ovarian syndrome. Diabetes Res Clin Pract. 2008;80(2):289–292.
    1. Rosenfield RL. Clinical review: identifying children at risk for polycystic ovary syndrome. J Clin Endocrinol Metab. 2007;92(3):787–796.
    1. Nicandri KF, Hoeger K. Diagnosis and treatment of polycystic ovarian syndrome in adolescents. Curr Opin Endocrinol Diabetes Obes. 2012;19(6):497–504.
    1. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocrin Rev. 1997;18:774–800.
    1. Carmina E, Lobo R. Use of fasting blood to assess the prevalence of insulin resistance in women with polycystic ovary syndrome. Fertil Steril. 2004;82:661–665.
    1. Schachter M, Raziel A, Friedler S, Strassburger D, Bern O, Ron-El R. Insulin resistance in patients with polycystic ovary syndrome is associated with elevated plasma homocysteine. Hum Reprod. 2003;18:721–727.
    1. Yildiz BO, Haznedaroglu IC, Kirazli S, Bayraktar M. Global fibrinolytic capacity is decreased in polycystic ovary syndrome, suggesting a prothrombotic state. J Clin Endocrinol Metab. 2002;87:3871–3875.
    1. Dunaif A, Sega KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes. 1989;38:1165–1174.
    1. Moran LJ, Misso ML, Wild RA, Norman RJ. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2010;16(4):347–363.
    1. NCEP Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III) JAMA. 2001;285:2486–2497.
    1. Dunaif A, Xia J, Book CB, Schenker E, Tang Z. Excessive insulin receptor serine phosphorylation in cultured fibroblasts and in skeletal muscle. A potential mechanism for insulin resistance in the polycystic ovary syndrome. J Clin Invest. 1995;96:801–810.
    1. Abdallah MA, Awwad J. The pathophysiology of polycystic ovary syndrome. In: Allahbadia GN, Agrawal R, editors. Polycystic Ovary Syndrome. Kent, UK: Anshan, Ltd; 2007. pp. 93–101.
    1. Ehrmann D, Sturis J, Byrne M, Karrison T, Rosenfield R, Polonsky K. Insulin secretory defects in polycystic ovary syndrome: relationship to insulin sensitivity and family history of non-insulin dependent diabetes mellitus. J Clin Invest. 1995;96:520–527.
    1. O’Meara NM, Blackman JD, Erhman DA. Defects in β-cell function and insulin action in functional ovarian hyperandrogenism. J Clin Endocrinol Metab. 1993;76:1241–1247.
    1. Ehrmann DA, Breda E, Cavaghan MK, et al. Insulin secretory responses to rising and falling glucose concentrations are delayed in subjects with impaired glucose tolerance. Diabetologica. 2002;45(4):509–517.
    1. Ehrmann DA, Breda E, Corcoran MC, et al. Impaired beta-cell compensation to dexamethasone-induced hyperglycemia in women with polycystic ovary syndrome. Am J Physiol Endocrinol Metab. 2004;287(2):E241–E246.
    1. Dunaif A, Finegood DT. β-cell dysfunction independent of obesity and glucose intolerance in the polycystic ovary syndrome. J Clin Endocrinol Metab. 1996;81:942–947.
    1. Legro RS, Gnatuk CL, Kunselman AR, Dunaif A. Changes in glucose tolerance over time in women with polycystic ovary syndrome: a controlled study. J Clin Endocrinol Metab. 2005;90:3236–3242.
    1. Ehrmann DA, Barnes RB, Rosenfield RL, Cavaghan MK, Imperial J. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care. 1999;22:141–146.
    1. 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;84:165–169.
    1. Harris MI, Hadden WC, Knowler WC, Bennett PH. Prevalence of diabetes and impaired glucose tolerance and plasma glucose levels in U.S. population aged 20–74 yr. Diabetes. 1987;36:523–534.
    1. Wild RA, Rizzo M, Clifton S, Carmina E. Lipid levels in polycystic ovary syndrome: systematic review and meta-analysis. Fertil Steril. 2011;95(3):1073–1079.
    1. Legro RS, Blanche P, Krauss RM, Lobo RA. Alterations in low-density lipoprotein and high-density lipoprotein subclasses among Hispanic women with polycytic ovary syndrome: influence of insulin and genetic factors. Fertil Steril. 1999;72(6):990–995.
    1. Dejager S, Pichard C, Giral P, et al. Smaller LDL particle size in women with polycystic ovary syndrome compared to controls. Clin Endocrinol (Oxf) 2001;54(4):455–462.
    1. Pirwany IR, Fleming R, Greer IA, Packard CJ, Sattar N. Lipids and lipoprotein subfractions in women with PCOS: relationship to metabolic and endocrine parameters. Clin Endocrinol (Oxf) 2001;54(4):447–453.
    1. Krauss RM, Siri PW. Metabolic abnormalities: triglyceride and low-density lipoprotein. Endocrinol Metab Clin N Am. 2004;33:405–415.
    1. Diamanti-Kandarakis E, Spina G, Kouli C, Migdalism I. Increased endothelin-1 levels in women with polycystic ovary syndrome and the beneficial effect of metformin therapy. J Clin Endocrinol Metab. 2001;86(10):4666–4673.
    1. Cascella T, Palomba S, Tauchmanova L, et al. Serum aldosterone concentration and cardiovascular risk in women with polycystic ovarian syndrome. J Clin Endocrinol Metab. 2006;91:4395–4400.
    1. Bentley-Lewis R, Seely E, Dunaif A. Ovarian hypertension: polycystic ovary syndrome. Endocrinol Metab Clin North Am. 2011;40:433–449.
    1. Lo JC, Feigenbaum SL, Yand J, Pressman AR, Selby JV, Go AS. Epidemiology and adverse cardiovascular risk profile of diagnosed polycystic ovary syndrome. J Clin Endocrinol Metab. 2006;91:1357–1363.
    1. Vrbikova J, Cifkova R, Jirkovska A, et al. Cardiovascular risk factors in young Czech females with polycystic ovary syndrome. Hum Reprod. 2003;18(5):980–894.
    1. Elting MW, Korsen TJM, Bezemer PD, Schoemaker J. Prevalence of diabetes mellitus, hypertension and cardiac complaints in a follow-up study of Dutch PCOS population. Hum Reprod. 2001;16:556–560.
    1. Wild S, Pierpoint T, McKeigue P, Jacobs H. Cardiovascular disease in women with polycystic ovary syndrome at long-term follow-up: a retrospective cohort study. Clin Endocrinol (Oxf) 2000;52:595–600.
    1. Schmidt J, Landin-Wilhelmsen K, Brannstrom M, Dahlgren E. Cardiovascular disease and risk factors in PCOS women of postmenopausal age: a 21-year controlled follow-up study. J Clin Endocrinol Metab. 2011;96(12):3794–3803.
    1. Shaw LJ, Bairey Merz CN, Azziz R, et al. Postmenopausal women with a history of irregular menses and elevated androgen measurements at high risk for worsening cardiovascular event-free survival: Results from the National Institutes of Health-National Heart, Lung, and Blood Institute Sponsored Women’s Ischemia Syndrome Evaluation. J Clin Endocrinol Metab. 2008;93:1276–1284.
    1. Solomon CG, Hu FB, Dunaif A, et al. Menstrual cycle irregularity and risk for future cardiovascular disease. J Clin Endocrinol Metab. 2002;87:2013–2017.
    1. Belanger CF, Hennekens CH, Rosner B, Speizer FE. The nurses’ health study. Am J Nurs. 1978;78:1039–1040.
    1. Arad Y, Spadaro LA, Goodman K, Newstein D, Guerci AD. Prediction of coronary events with electron beam computed tomography. J Am Coll Cardiol. 2000;36:1253–1260.
    1. Christian RC, Dumesic DA, Behrenbeck T, Oberg AL, Sheedy PF, Fitzpatrick LA. Prevalence and predictors of coronary artery calcification in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003;88:2562–2568.
    1. Talbott EO, Zborowski JV, Rager JR, Boudreaux MY, Edmundowicz DA, Guzick DS. Evidence for an association between metabolic cardiovascular syndrome and coronary and aortic calcification among women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2004;89:5454–5461.
    1. Shroff R, Kerchner A, Maifeld M, Van Beek E, Jagasia D, Dokras A. Young obese women with polycystic ovary syndrome have evidence of early coronary atherosclerosis. J Clin Endocrinol Metab. 2007;92:4609–4614.
    1. Talbott EO, Zborowski JV, Rager J, Stragand JR. Is there an independent effect of polycystic ovary syndrome (PCOS) and menopause on the prevalence of subclinical atherosclerosis in middle aged women? Vasc Health Risk Manag. 2008;4:453–462.
    1. Talbott EO, Guzick DS, Sutton-Tyrrell K, et al. Evidence for association between polycystic ovary syndrome and premature carotid atherosclerosis in middle-aged women. Arteriosler Thromb Vasc Biol. 2000;20:2414–2421.
    1. Guzick DS, Talbot EO, Sutton-Tyrrell K. Carotid atherosclerosis in women with polycystic ovary syndrome: initial results from a case-control study. Am J Obstet Gynecol. 1996;174:1224–1232.
    1. Carmina E, Orio F, Palomba S, et al. Endothelial dysfunction in PCOS: role of obesity and adipose hormones. Am J Med. 2006;119:356. e351–e356.
    1. Vryonidou A, Papatheodorou A, Tavridou A, et al. Association of hyperandrogenemic and metabolic phenotype with carotid intima-media thickness in young women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2005;2005:2740–2746.
    1. Orio F, Jr, Palomba S, Cascella T, et al. Early impairment of endothelial structure and function in young normal-weight women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2004;89:4588–4593.
    1. Alexander CJ, Tangchitnob EP, Lepor NE. Polycystic ovary syndrome: a major unrecognized cardiovascular risk factor in women. Rev Obstet Gynecol. 2009;2(4):232–239.
    1. Hollinrake E, Abreu A, Maifeld M, Van Voorhis BJ, Dokras A. Increased risk of depressive disorders in women with polycystic ovary syndrome. Fertil Steril. 2007;87:1369–1376.
    1. Dokras A, Clifton S, Futterweit W, Wild R. Increased risk for abnormal depression scores in women with polycystic ovary syndrome: a systematic review and meta-analysis. Obstet Gynecol. 2011;117(1):145–152.
    1. Klipstein KG, Goldberg JF. Screening for bipolar disorder in women with polycystic ovary syndrome: a pilot study. J Affect Disord. 2006;91(2–3):205–209.
    1. Rassi A, Veras AB, dos Reis M, et al. Prevalence of psychiatric disorders in patients with polycystic ovary syndrome. Compr Psychiatry. 2010;51:599–602.
    1. Merikangas KR, Spence A, Kupfer DJ. Linkage studies of bipolar disorder: methodologic and analytic issues. Arch Gen Psychiatry. 1989;46:1137–1141.
    1. Dokras A, Clifton S, Futterweit W, Wild R. Increased prevalence of anxiety symptoms in women with polycystic ovary syndrome: systematic review and meta-analysis. Fertil Steril. 2012;97(1):225–230.
    1. Badawy A, Elnashar A. Treatment options for polycystic ovary syndrome. Int J Womens Health. 2011;3:25–35.
    1. ACOG Committee on Practice Bulletins – Gynecology ACOG Practice Bulletin No 108: Polycystic ovary syndrome. Obstet Gynecol. 2009;114(4):936–949.
    1. Lexi-Comp Online™, Lexi-Drugs Online™. Hudson, Ohio: Lexi-Comp, Inc; Aug 9, 2013.
    1. Bates GW, Propst AM. Polycystic ovarian syndrome management options. Obstet Gynecol Clin North Am. 2012;39(4):495–506.
    1. Pasquali R, Pelusi C, Genghini S, Caciari M, Gambineri A. Obesity and reproductive disorders in women. Hum Reprod Update. 2003;9(4):359–372.
    1. Froen JF, Arnestad M, Frey K, Vege A, Saugstad OD, Stray-Pedersen B. Risk factors for sudden intrauterine unexplained death: epidemiologic characteristics of singleton cases in Oslo, Norway,1986–1995. Am J Obstet Gynecol. 2001;184(4):694–702.
    1. Imani B, Eijkemans MJ, te Velde ER, Habbema JD, Fauser BC. Predictors of patients remaining anovulatory during clomiphene citrate induction of ovulation in nomogonadotropic oligoamenorrheic infertility. J Clin Endocrinol Metab. 1998;83(7):2361–2365.
    1. Imani B, Eijkemans MJ, te Velde ER, Habbema JD, Fauser BC. Predictors of chances to conceive in ovulatory patients during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorheic infertility. J Clin Endocrinol Metab. 1999;84(5):1617–1622.
    1. Mulders AG, Laven JS, Eijkemans MJ, Hughes EG, Fauser BC. Patient predictors for outcome of gonadotrophin ovulation induction in women with normogonadotrophic anovulatory infertility: a meta-analysis. Hum Reprod Update. 2003;9(5):429–449.
    1. Balen AH, Platteau P, Andersen AN, Devroey P, Sorensen P, Helmgaard L. The influence of body weight on response to ovulation induction with gonadotrophin in 335 women with World Health Organization group II anovulatory infertility. BJOG. 2006;113:1195–1202.
    1. Gjonnaess H. Ovarian electrocautery in the treatment of women with polycystic ovary syndrome (PCOS). Factors affecting the results. Acta Obstet Gynecol Scand. 1994;73(5):407–412.
    1. Homburg R. The management of infertility associated with polycystic ovary syndrome. Reprod Biol Endocrinol. 2003;1:109.
    1. Escobar-Morreale HF, Botella-Carretero JI, Alvarez-Blasco F, Sancho J, San Millan JL. The polycystic ovary syndrome associated with morbid obesity may resolve after weight loss induced by bariatric surgery. J Clin Endocrinol Metab. 2005;90(12):6364–6369.
    1. Eid GM, Cottam DR, Velcu LM, et al. Effective treatment of polycystic ovarian syndrome with Roux-en-Y gastric bypass. Surg Obes Relat Dis. 2005;1(2):77–80.
    1. Jamal M, Gunay Y, Capper A, Eid A, Heitshusen D, Samuel I. Roux-en-Y gastric bypass ameliorates polycystic ovary syndrome and dramatically improves conception rates: a 9-year analysis. Surg Obes Relat Dis. 2012;8(4):440–444.
    1. Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group Consensus on infertility treatment related to polycystic ovary syndrome. Fertil Steril. 2008;89(3):505–522.
    1. Balen AH. Ovulation induction in the management of anovulatory polycystic ovary syndrome. Mol Cell Endocrinol. 2013;373(1–2):77–82.
    1. Costello MF, Misso ML, Wong J, et al. The treatment of infertility in polycystic ovary syndrome: a brief update. Aust N Z J Obstet Gynaecol. 2012;52:400–403.
    1. Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiroinositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev. 2012;5:CD003053.
    1. Morin-Papunen L, Rantala AS, Unkila-Kallio L, et al. Metformin improves pregnancy and live-birth rates in women with polycystic ovary syndrome (PCOS): a multicenter, double-blind, placebo-controlled randomized trial. J Clin Endocrinol Metab. 2012;97:1492–1500.
    1. Kjotrod SB, Carlsen SM, Rasmussen PE, et al. Use of metformin before and during assisted reproductive technology in non-obese young infertile women with polycystic ovary syndrome: a prospective, randomized, double-blind, multi-centre study. Hum Reprod. 2011;26(8):2045–2053.
    1. Casper RF, Mitwally MF. Use of the aromatase inhibitor letrozole for ovulation induction in women with polycystic ovarian syndrome. Clin Obstet Gynecol. 2011;54(4):685–695.
    1. Pritts EA. Letrozole for ovulation induction and controlled ovarian hyperstimulation. Curr Opin Obstet Gynecol. 2010;22(4):289–294.
    1. Holzer H, Casper R, Tulandi T. A new era in ovulation induction. Fertil Steril. 2006;85(2):277–284.
    1. Misso ML, Wong JL, Teede HJ, et al. Aromatase inhibitors for PCOS: a systematic review and meta-analysis. Hum Reprod Update. 2012;18(3):301–312.
    1. Kar S. Clomiphene citrate or letrozole as first-line ovulation induction drug in infertile PCOS women. J Hum Reprod Sci. 2012;5(3):262–265.
    1. Legro RS, Kunselman AR, Brzyski RG, et al. The pregnancy in polycystic ovary syndrome II (PPCOS II) trial: rationale and design of a double-blind randomized trial of clomiphene and letrozole for the treatment of infertility in women with polycystic ovary syndrome. Contemp Clin Trials. 2012;33(3):470–481.
    1. Perales-Puchalt A, Legro RS. Ovulation induction in women with polycystic ovary syndrome. Steroids. 2013;78:767–772.
    1. Christin-Maitre S, Hugues JN. A comparative randomized multicentric study comparing the step-up versus step-down protocol in polycystic ovary syndrome. Hum Reprod. 2003;18(8):1626–1631.
    1. Homburg R. Ovulation induction for women with polycystic ovary syndrome. In: Kovacs G, Norman R, editors. Polycystic Ovary Syndrome. 2nd ed. Cambridge, UK: Cambridge University Press; 2007. pp. 140–158.
    1. Homburg R, Hendriks ML, Konig TE, et al. Clomifene citrate or low-dose FSH for the first-line treatment of infertile women with anovulation associated with polycystic ovary syndrome: a prospective randomized multinational study. Hum Reprod. 2012;17(2):468–473.
    1. Gjonnaess H. Polycystic ovarian syndrome treated by ovarian electrocautery through the laparoscope. Fertil Steril. 1984;41(1):20–25.
    1. Amer SA, Li TC, Ledger WL. Ovulation induction using laparoscopic ovarian drilling in women with polycystic ovarian syndrome: predictors of success. Hum Reprod. 2004;19(8):1719–1724.
    1. Amer SA, Li TC, Metwally M, Emarh M, Ledger WL. Randomized controlled trial comparing laparosopic ovarian diathermy with clomiphene citrate as a first-line method of ovulation induction in women with polycystic ovary syndrome. Hum Reprod. 2009;24(1):219–225.
    1. Farquhar C, Lilford RJ, Marjoribanks J, Vandekerckhove P. Laparoscopic ‘drilling’ by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database Syst Rev. 2007;18(3):CD001122.
    1. Farquhar C, Brown J, Majoribanks J. Laparoscopic drilling by diathermy of laser for ovulation induction in anovulatory polycystic ovary syndrome. Cochrane Database Syst Rev. 2012;13(6):CD001122.
    1. Heijnen EM, Eijkemans MJ, Hughes EG, Laven JS, Macklon NS, Fauser BC. A meta-analysis of outcomes of conventional IVF in women with polycystic ovary syndrome. Hum Reprod Update. 2006;12(1):13–21.
    1. Al-Inany HG, Youssef MA, Aboulghar M, et al. Gonadotrophin-releasing hormone antagonists for assisted reproductive technology. Cochrane Database Syst Rev. 2011;11(5):CD001750.
    1. Palomba S, Falbo A, Carrillo L, et al. Metformin reduces risk of ovarian hyperstimulation syndrome in patients with polycystic ovary syndrome during gonadotropin-stimulated in vitro fertilization cycles: a randomized, controlled trial. Fertil Steril. 2011;96(6):1384–1390.
    1. Bargiota A, Diamanti-Kandarakis E. The effects of old, new, and emerging medicines on metabolic aberrations in PCOS. Ther Adv Endocrinol Metab. 2012;3(1):27–47.

Source: PubMed

3
Subskrybuj