Semin Reprod Med 2017; 35(03): 271-281
DOI: 10.1055/s-0037-1603096
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Polycystic Ovarian Syndrome: Long-Term Health Consequences

Temeka Zore
1   Department of Obstetrics and Gynecology, David Geffen School of Medicine, UCLA, Los Angeles, California
,
Nikhil V. Joshi
1   Department of Obstetrics and Gynecology, David Geffen School of Medicine, UCLA, Los Angeles, California
,
Daria Lizneva
2   Department of Obstetrics and Gynecology, Medical College of Georgia, Augusta University, Augusta, Georgia
,
Ricardo Azziz
1   Department of Obstetrics and Gynecology, David Geffen School of Medicine, UCLA, Los Angeles, California
2   Department of Obstetrics and Gynecology, Medical College of Georgia, Augusta University, Augusta, Georgia
3   Office of Academic Health and Hospital Affairs, State University of New York System Administration, Albany, New York
› Author Affiliations
Further Information

Publication History

Publication Date:
28 June 2017 (online)

Abstract

Polycystic ovarian syndrome (PCOS) is the most common endocrinopathy in women and can be associated with significant adverse sequelae that can affect overall long-term health and well-being. This review provides a succinct but comprehensive overview of our current understanding concerning the known morbidities of PCOS, beginning with a review of the importance of the different phenotypes of PCOS in determining long-term morbidity, the confounding impact of obesity on health outcomes in PCOS, and the immediate short-term consequences of the disorder (including dermatologic, reproductive, and mood disturbances). The longer-term morbidities of PCOS are then reviewed including metabolic consequences (impaired glucose tolerance and type 2 diabetes mellitus, metabolic syndrome, and nonalcoholic fatty liver disease), dyslipidemia and vascular dysfunction (including hypertension and increased incidences of cerebrovascular accidents and thromboembolisms on oral contraceptives), neoplastic (primarily endometrial adenocarcinoma), and mental health disorders (including greater incidences of depressive and anxiety disturbances and psychosexual dysfunction). In conclusion, strategies for the prevention and amelioration of long-term morbidities in PCOS are presented.

 
  • References

  • 1 Azziz R, Carmina E, Chen Z. , et al. Polycystic ovary syndrome. Nat Rev Dis Primers 2016; 2: 16057
  • 2 Lizneva D, Suturina L, Walker W, Brakta S, Gavrilova-Jordan L, Azziz R. Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertil Steril 2016; 106 (01) 6-15
  • 3 Bozdag G, Mumusoglu S, Zengin D, Karabulut E, Yildiz BO. The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod 2016; 31 (12) 2841-2855
  • 4 Zawadzki JK, Dunaif A. Diagnostic Criteria for Polycystic Ovary Syndrome: Towards a Rational Approach. Boston, MA: Blackwell Scientific Publications; 1992
  • 5 Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004; 19 (01) 41-47
  • 6 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 (01) 19-25
  • 7 Azziz R, Carmina E, Dewailly D. , et al; Androgen Excess Society. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab 2006; 91 (11) 4237-4245
  • 8 Fauser BC, Tarlatzis BC, Rebar RW. , 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 (01) 28-38.e25
  • 9 Lizneva D, Kirubakaran R, Mykhalchenko K, Suturina L, Chernukha G, Diamond MP, Azziz R. Phenotypes and body mass in women with polycystic ovary syndrome identified in referral versus unselected populations: systematic review and meta-analysis. Fertil Steril 2016; 106 (06) 1510-1520
  • 10 Carmina E, Campagna AM, Lobo RA. A 20-year follow-up of young women with polycystic ovary syndrome. Obstet Gynecol 2012; 119 (2, Pt 1): 263-269
  • 11 Ogden CL, Carroll MD, Fryar CD, Flegal KM. Prevalence of obesity among adults and youth: United States, 2011-2014. NCHS Data Brief 2015; (219) 1-8
  • 12 Azziz R, Ehrmann D, Legro RS. , et al; PCOS/Troglitazone Study Group. Troglitazone improves ovulation and hirsutism in the polycystic ovary syndrome: a multicenter, double blind, placebo-controlled trial. J Clin Endocrinol Metab 2001; 86 (04) 1626-1632
  • 13 Ehrmann DA. Polycystic ovary syndrome. N Engl J Med 2005; 352 (12) 1223-1236
  • 14 Carmina E, Koyama T, Chang L, Stanczyk FZ, Lobo RA. Does ethnicity influence the prevalence of adrenal hyperandrogenism and insulin resistance in polycystic ovary syndrome?. Am J Obstet Gynecol 1992; 167 (06) 1807-1812
  • 15 Carmina E, Legro RS, Stamets K, Lowell J, Lobo RA. Difference in body weight between American and Italian women with polycystic ovary syndrome: influence of the diet. Hum Reprod 2003; 18 (11) 2289-2293
  • 16 Lim SS, Davies MJ, Norman RJ, Moran LJ. Overweight, obesity and central obesity in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update 2012; 18 (06) 618-637
  • 17 Luque-Ramírez M, Alpañés M, Sanchón R, Fernández-Durán E, Ortiz-Flores AE, Escobar-Morreale HF. Referral bias in female functional hyperandrogenism and polycystic ovary syndrome. Eur J Endocrinol 2015; 173 (05) 603-610
  • 18 Vrbíková J, Cibula D, Dvoráková K. , et al. Insulin sensitivity in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2004; 89 (06) 2942-2945
  • 19 Morales AJ, Laughlin GA, Bützow T, Maheshwari H, Baumann G, Yen SS. Insulin, somatotropic, and luteinizing hormone axes in lean and obese women with polycystic ovary syndrome: common and distinct features. J Clin Endocrinol Metab 1996; 81 (08) 2854-2864
  • 20 Escobar-Morreale HF, Carmina E, Dewailly D. , et al. Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society. Hum Reprod Update 2012; 18 (02) 146-170
  • 21 DeUgarte CM, Woods KS, Bartolucci AA, Azziz R. Degree of facial and body terminal hair growth in unselected black and white women: toward a populational definition of hirsutism. J Clin Endocrinol Metab 2006; 91 (04) 1345-1350
  • 22 Quinn M, Shinkai K, Pasch L, Kuzmich L, Cedars M, Huddleston H. Prevalence of androgenic alopecia in patients with polycystic ovary syndrome and characterization of associated clinical and biochemical features. Fertil Steril 2014; 101 (04) 1129-1134
  • 23 Balen AH, Morley LC, Misso M. , et al. The management of anovulatory infertility in women with polycystic ovary syndrome: an analysis of the evidence to support the development of global WHO guidance. Hum Reprod Update 2016; 22 (06) 687-708
  • 24 Apridonidze T, Essah PA, Iuorno MJ, Nestler JE. Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2005; 90 (04) 1929-1935
  • 25 Joham AE, Teede HJ, Ranasinha S, Zoungas S, Boyle J. Prevalence of infertility and use of fertility treatment in women with polycystic ovary syndrome: data from a large community-based cohort study. J Womens Health (Larchmt) 2015; 24 (04) 299-307
  • 26 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
  • 27 Joham AE, Boyle JA, Ranasinha S, Zoungas S, Teede HJ. Contraception use and pregnancy outcomes in women with polycystic ovary syndrome: data from the Australian Longitudinal Study on Women's Health. Hum Reprod 2014; 29 (04) 802-808
  • 28 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 (01) 145-152
  • 29 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 (01) 225-30.e2
  • 30 Veltman-Verhulst SM, Boivin J, Eijkemans MJ, Fauser BJ. Emotional distress is a common risk in women with polycystic ovary syndrome: a systematic review and meta-analysis of 28 studies. Hum Reprod Update 2012; 18 (06) 638-651
  • 31 Ezeh U, Pall M, Mathur R. , et al. Effects of endogenous androgens and abdominal fat distribution on the interrelationship between insulin and non-insulin-mediated glucose uptake in females. J Clin Endocrinol Metab 2013; 98 (04) 1541-1548
  • 32 Carmina E, Bucchieri S, Esposito A. , et al. Abdominal fat quantity and distribution in women with polycystic ovary syndrome and extent of its relation to insulin resistance. J Clin Endocrinol Metab 2007; 92 (07) 2500-2505
  • 33 Dumesic DA, Akopians AL, Madrigal VK. , et al. Hyperandrogenism accompanies increased intra-abdominal fat storage in normal weight polycystic ovary syndrome women. J Clin Endocrinol Metab 2016; 101 (11) 4178-4188
  • 34 Carmina E, Bucchieri S, Mansueto P, Rini G, Ferin M, Lobo RA. Circulating levels of adipose products and differences in fat distribution in the ovulatory and anovulatory phenotypes of polycystic ovary syndrome. Fertil Steril 2009; 91 (4, Suppl): 1332-1335
  • 35 Dunaif A, Finegood DT. Beta-cell dysfunction independent of obesity and glucose intolerance in the polycystic ovary syndrome. J Clin Endocrinol Metab 1996; 81 (03) 942-947
  • 36 Chazenbalk G, Trivax BS, Yildiz BO. , et al. Regulation of adiponectin secretion by adipocytes in the polycystic ovary syndrome: role of tumor necrosis factor-alpha. J Clin Endocrinol Metab 2010; 95 (02) 935-942
  • 37 Carmina E, Chu MC, Moran C. , et al. Subcutaneous and omental fat expression of adiponectin and leptin in women with polycystic ovary syndrome. Fertil Steril 2008; 89 (03) 642-648
  • 38 Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev 2012; 33 (06) 981-1030
  • 39 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 (07) 2278-2286
  • 40 Guo Y, Qi Y, Yang X. , et al. Association between polycystic ovary syndrome and gut microbiota. PLoS One 2016; 11 (04) e0153196
  • 41 Shroff R, Syrop CH, Davis W, Van Voorhis BJ, Dokras A. Risk of metabolic complications in the new PCOS phenotypes based on the Rotterdam criteria. Fertil Steril 2007; 88 (05) 1389-1395
  • 42 Diamanti-Kandarakis E, Panidis D. Unravelling the phenotypic map of polycystic ovary syndrome (PCOS): a prospective study of 634 women with PCOS. Clin Endocrinol (Oxf) 2007; 67 (05) 735-742
  • 43 Zhao X, Zhong J, Mo Y, Chen X, Chen Y, Yang D. Association of biochemical hyperandrogenism with type 2 diabetes and obesity in Chinese women with polycystic ovary syndrome. Int J Gynaecol Obstet 2010; 108 (02) 148-151
  • 44 Brower M, Brennan K, Pall M, Azziz R. The severity of menstrual dysfunction as a predictor of insulin resistance in PCOS. J Clin Endocrinol Metab 2013; 98 (12) E1967-E1971
  • 45 Moran LJ, Misso ML, Wild RA, Norman RJ. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update 2010; 16 (04) 347-363
  • 46 Vassilatou E, Vassiliadi DA, Salambasis K. , et al. Increased prevalence of polycystic ovary syndrome in premenopausal women with nonalcoholic fatty liver disease. Eur J Endocrinol 2015; 173 (06) 739-747
  • 47 Romanowski MD, Parolin MB, Freitas AC, Piazza MJ, Basso J, Urbanetz AA. Prevalence of non-alcoholic fatty liver disease in women with polycystic ovary syndrome and its correlation with metabolic syndrome. Arq Gastroenterol 2015; 52 (02) 117-123
  • 48 Ehrmann DA, Liljenquist DR, Kasza K, Azziz R, Legro RS, Ghazzi MN. ; PCOS/Troglitazone Study Group. Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2006; 91 (01) 48-53
  • 49 Dokras A, Bochner M, Hollinrake E, Markham S, Vanvoorhis B, Jagasia DH. Screening women with polycystic ovary syndrome for metabolic syndrome. Obstet Gynecol 2005; 106 (01) 131-137
  • 50 Valkenburg O, Steegers-Theunissen RP, Smedts HP. , et al. A more atherogenic serum lipoprotein profile is present in women with polycystic ovary syndrome: a case-control study. J Clin Endocrinol Metab 2008; 93 (02) 470-476
  • 51 Lo JC, Feigenbaum SL, Yang J, Pressman AR, Selby JV, Go AS. Epidemiology and adverse cardiovascular risk profile of diagnosed polycystic ovary syndrome. J Clin Endocrinol Metab 2006; 91 (04) 1357-1363
  • 52 Elting MW, Korsen TJ, Bezemer PD, Schoemaker J. Prevalence of diabetes mellitus, hypertension and cardiac complaints in a follow-up study of a Dutch PCOS population. Hum Reprod 2001; 16 (03) 556-560
  • 53 Christian RC, Dumesic DA, Behrenbeck T, Oberg AL, Sheedy II PF, Fitzpatrick LA. Prevalence and predictors of coronary artery calcification in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2003; 88 (06) 2562-2568
  • 54 Carmina E. Polycystic ovary syndrome: metabolic consequences and long-term management. Scand J Clin Lab Invest Suppl 2014; 244: 23-26 , discussion 26
  • 55 Schmidt J, Landin-Wilhelmsen K, Brännström 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
  • 56 Merz CN, Shaw LJ, Azziz R. , et al. Cardiovascular disease and 10-year mortality in postmenopausal women with clinical features of polycystic ovary syndrome. J Womens Health (Larchmt) 2016; 25 (09) 875-881
  • 57 Anderson SA, Barry JA, Hardiman PJ. Risk of coronary heart disease and risk of stroke in women with polycystic ovary syndrome: a systematic review and meta-analysis. Int J Cardiol 2014; 176 (02) 486-487
  • 58 Bird ST, Hartzema AG, Brophy JM, Etminan M, Delaney JA. Risk of venous thromboembolism in women with polycystic ovary syndrome: a population-based matched cohort analysis. CMAJ 2013; 185 (02) E115-E120
  • 59 Dumesic DA, Lobo RA. Cancer risk and PCOS. Steroids 2013; 78 (08) 782-785
  • 60 Barry JA, Azizia MM, Hardiman PJ. Risk of endometrial, ovarian and breast cancer in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update 2014; 20 (05) 748-758
  • 61 Hardiman P, Pillay OC, Atiomo W. Polycystic ovary syndrome and endometrial carcinoma. Lancet 2003; 361 (9371): 1810-1812
  • 62 Haoula Z, Salman M, Atiomo W. Evaluating the association between endometrial cancer and polycystic ovary syndrome. Hum Reprod 2012; 27 (05) 1327-1331
  • 63 Gottschau M, Kjaer SK, Jensen A, Munk C, Mellemkjaer L. Risk of cancer among women with polycystic ovary syndrome: a Danish cohort study. Gynecol Oncol 2015; 136 (01) 99-103
  • 64 Shobeiri F, Jenabi E. The association between polycystic ovary syndrome and breast cancer: a meta-analysis. Obstet Gynecol Sci 2016; 59 (05) 367-372
  • 65 Kim J, Mersereau JE, Khankari N. , et al. Polycystic ovarian syndrome (PCOS), related symptoms/sequelae, and breast cancer risk in a population-based case-control study. Cancer Causes Control 2016; 27 (03) 403-414
  • 66 Hvidtfeldt UA, Gunter MJ, Lange T. , et al. Quantifying mediating effects of endogenous estrogen and insulin in the relation between obesity, alcohol consumption, and breast cancer. Cancer Epidemiol Biomarkers Prev 2012; 21 (07) 1203-1212
  • 67 Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008; 371 (9612): 569-578
  • 68 Wolf I, Sadetzki S, Catane R, Karasik A, Kaufman B. Diabetes mellitus and breast cancer. Lancet Oncol 2005; 6 (02) 103-111
  • 69 Col NF, Ochs L, Springmann V, Aragaki AK, Chlebowski RT. Metformin and breast cancer risk: a meta-analysis and critical literature review. Breast Cancer Res Treat 2012; 135 (03) 639-646
  • 70 Schildkraut JM, Schwingl PJ, Bastos E, Evanoff A, Hughes C. Epithelial ovarian cancer risk among women with polycystic ovary syndrome. Obstet Gynecol 1996; 88 (4, Pt 1): 554-559
  • 71 Wise LA, Palmer JR, Stewart EA, Rosenberg L. Polycystic ovary syndrome and risk of uterine leiomyomata. Fertil Steril 2007; 87 (05) 1108-1115
  • 72 Wong JY, Gold EB, Johnson WO, Lee JS. Circulating sex hormones and risk of uterine fibroids: study of Women's Health Across the Nation (SWAN). J Clin Endocrinol Metab 2016; 101 (01) 123-130
  • 73 Abdel-Gadir A, Oyawoye OO, Chander BP. Coexistence of polycystic ovaries and uterine fibroids and their combined effect on the uterine artery blood flow in relation to age and parity. J Reprod Med 2009; 54 (06) 347-352
  • 74 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 (06) 1369-1376
  • 75 Dokras A. Mood and anxiety disorders in women with PCOS. Steroids 2012; 77 (04) 338-341
  • 76 Elsenbruch S, Hahn S, Kowalsky D. , et al. Quality of life, psychosocial well-being, and sexual satisfaction in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2003; 88 (12) 5801-5807
  • 77 National Institute of Mental Health. The Numbers Count: Mental Disorders in America, 2001. NIH Publication No. 01–4584. Bethesda, MD: U.S. Department of Health and Human Services, National Institutes of Health; 2001
  • 78 Hasin DS, Goodwin RD, Stinson FS, Grant BF. Epidemiology of major depressive disorder: results from the National Epidemiologic Survey on Alcoholism and Related Conditions. Arch Gen Psychiatry 2005; 62 (10) 1097-1106
  • 79 Brawman-Mintzer O, Lydiard RB, Emmanuel N. , et al. Psychiatric comorbidity in patients with generalized anxiety disorder. Am J Psychiatry 1993; 150 (08) 1216-1218
  • 80 Cinar N, Kizilarslanoglu MC, Harmanci A. , et al. Depression, anxiety and cardiometabolic risk in polycystic ovary syndrome. Hum Reprod 2011; 26 (12) 3339-3345
  • 81 Barry JA, Kuczmierczyk AR, Hardiman PJ. Anxiety and depression in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod 2011; 26 (09) 2442-2451
  • 82 Li Y, Li Y, Yu Ng EH. , et al. Polycystic ovary syndrome is associated with negatively variable impacts on domains of health-related quality of life: evidence from a meta-analysis. Fertil Steril 2011; 96 (02) 452-458
  • 83 Månsson M, Norström K, Holte J, Landin-Wilhelmsen K, Dahlgren E, Landén M. Sexuality and psychological wellbeing in women with polycystic ovary syndrome compared with healthy controls. Eur J Obstet Gynecol Reprod Biol 2011; 155 (02) 161-165
  • 84 Cronin L, Guyatt G, Griffith L. , et al. Development of a health-related quality-of-life questionnaire (PCOSQ) for women with polycystic ovary syndrome (PCOS). J Clin Endocrinol Metab 1998; 83 (06) 1976-1987
  • 85 Guyatt G, Weaver B, Cronin L, Dooley JA, Azziz R. Health-related quality of life in women with polycystic ovary syndrome, a self-administered questionnaire, was validated. J Clin Epidemiol 2004; 57 (12) 1279-1287
  • 86 Azziz R, Marin C, Hoq L, Badamgarav E, Song P. Health care-related economic burden of the polycystic ovary syndrome during the reproductive life span. J Clin Endocrinol Metab 2005; 90 (08) 4650-4658
  • 87 Cao SF, Hu WL, Wu MM, Jiang LY. Effects of exercise intervention on preventing letrozole-exposed rats from polycystic ovary syndrome. Reprod Sci 2017; 24 (03) 456-462
  • 88 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 (01) 165-169
  • 89 Fauser BC, Tarlatzis BC, Rebar RW. , 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 (01) 28-38.e25
  • 90 Legro RS, Arslanian SA, Ehrmann DA. , et al; Endocrine Society. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2013; 98 (12) 4565-4592
  • 91 Kiddy DS, Hamilton-Fairley D, Bush A. , et al. Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome. Clin Endocrinol (Oxf) 1992; 36 (01) 105-111
  • 92 Moran LJ, Ko H, Misso M. , et al. Dietary composition in the treatment of polycystic ovary syndrome: a systematic review to inform evidence-based guidelines. Hum Reprod Update 2013; 19 (05) 432
  • 93 Knowler WC, Barrett-Connor E, Fowler SE. , et al; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346 (06) 393-403
  • 94 Salpeter SR, Buckley NS, Kahn JA, Salpeter EE. Meta-analysis: metformin treatment in persons at risk for diabetes mellitus. Am J Med 2008; 121 (02) 149-157.e2
  • 95 Naderpoor N, Shorakae S, de Courten B, Misso ML, Moran LJ, Teede HJ. Metformin and lifestyle modification in polycystic ovary syndrome: systematic review and meta-analysis. Hum Reprod Update 2015; 21 (05) 560-574
  • 96 Gao L, Zhao FL, Li SC. Statin is a reasonable treatment option for patients with polycystic ovary syndrome: a meta-analysis of randomized controlled trials. Exp Clin Endocrinol Diabetes 2012; 120 (06) 367-375