Semin Reprod Med 2012; 30(06): 496-506
DOI: 10.1055/s-0032-1328878
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Obesity and PCOS: Implications for Diagnosis and Treatment

Richard S. Legro
1   Department of Obstetrics and Gynecology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania
› Author Affiliations
Further Information

Publication History

Publication Date:
16 October 2012 (online)

Abstract

There appears to be an epidemic of both obesity and polycystic ovary syndrome (PCOS) in the world today. However, obesity per se is not a part of the phenotype in many parts of the world. Obesity is likely not a cause of PCOS, as the high prevalence of PCOS among relatively thin populations demonstrates. However, obesity does exacerbate many aspects of the phenotype, especially cardiovascular risk factors such as glucose intolerance and dyslipidemia. It is also associated with a poor response to infertility treatment and likely an increased risk for pregnancy complications in those women who do conceive. Although most treatments of obesity, with the exception of bariatric surgery, achieve modest reductions in weight and improvements in the PCOS phenotype, encouraging weight loss in the obese patient remains one of the front-line therapies. However, further studies are needed to identify the best treatments, and the role of lifestyle therapies in women of normal weight with PCOS is uncertain.

 
  • References

  • 1 Stein IF, Leventhal ML. Amenorrhea associated with polycystic ovaries. Am J Obstet Gynecol 1935; 29: 181-191
  • 2 Rebar R, Judd HL, Yen SS, Rakoff J, Vandenberg G, Naftolin F. Characterization of the inappropriate gonadotropin secretion in polycystic ovary syndrome. J Clin Invest 1976; 57 (5) 1320-1329
  • 3 Cumming DC, Reid RL, Quigley ME, Rebar RW, Yen SS. Evidence for decreased endogenous dopamine and opioid inhibitory influences on LH secretion in polycystic ovary syndrome. Clin Endocrinol (Oxf) 1984; 20 (6) 643-648
  • 4 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 (4) 1626-1632
  • 5 Legro RS, Barnhart HX, Schlaff WD , et al; Cooperative Multicenter Reproductive Medicine Network. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med 2007; 356 (6) 551-566
  • 6 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 (6) 2745-2749
  • 7 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 (9) 3078-3082
  • 8 Yildiz BO, Knochenhauer ES, Azziz R. Impact of obesity on the risk for polycystic ovary syndrome. J Clin Endocrinol Metab 2008; 93 (1) 162-168
  • 9 Azziz R. Controversy in clinical endocrinology: diagnosis of polycystic ovarian syndrome: the Rotterdam criteria are premature. J Clin Endocrinol Metab 2006; 91 (3) 781-785
  • 10 Carmina E, Chu MC, Longo RA, Rini GB, Lobo RA. Phenotypic variation in hyperandrogenic women influences the findings of abnormal metabolic and cardiovascular risk parameters. J Clin Endocrinol Metab 2005; 90 (5) 2545-2549
  • 11 Burgers JA, Fong SL, Louwers YV , et al. Oligoovulatory and anovulatory cycles in women with polycystic ovary syndrome (PCOS): what's the difference?. J Clin Endocrinol Metab 2010; 95 (12) E485-E489
  • 12 Panidis D, Tziomalos K, Misichronis G , et al. Insulin resistance and endocrine characteristics of the different phenotypes of polycystic ovary syndrome: a prospective study. Hum Reprod 2012; 27 (2) 541-549
  • 13 Johnstone EB, Rosen MP, Neril R , et al. The polycystic ovary post-Rotterdam: a common, age-dependent finding in ovulatory women without metabolic significance. J Clin Endocrinol Metab 2010; 95 (11) 4965-4972
  • 14 Willis D, Franks S. Insulin action in human granulosa cells from normal and polycystic ovaries is mediated by the insulin receptor and not the type-I insulin-like growth factor receptor. J Clin Endocrinol Metab 1995; 80 (12) 3788-3790
  • 15 Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997; 18 (6) 774-800
  • 16 Dunaif A, Graf M. Insulin administration alters gonadal steroid metabolism independent of changes in gonadotropin secretion in insulin-resistant women with the polycystic ovary syndrome. J Clin Invest 1989; 83 (1) 23-29
  • 17 Codner E, Iñíguez G, Villarroel C , et al. Hormonal profile in women with polycystic ovarian syndrome with or without type 1 diabetes mellitus. J Clin Endocrinol Metab 2007; 92 (12) 4742-4746
  • 18 Nestler JE, Jakubowicz DJ. Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. N Engl J Med 1996; 335 (9) 617-623
  • 19 Repaci A, Gambineri A, Pasquali R. The role of low-grade inflammation in the polycystic ovary syndrome. Mol Cell Endocrinol 2011; 335 (1) 30-41
  • 20 Adashi EY, Hsueh AJ, Yen SS. Insulin enhancement of luteinizing hormone and follicle-stimulating hormone release by cultured pituitary cells. Endocrinology 1981; 108 (4) 1441-1449
  • 21 Brothers KJ, Wu S, DiVall SA , et al. Rescue of obesity-induced infertility in female mice due to a pituitary-specific knockout of the insulin receptor. Cell Metab 2010; 12 (3) 295-305
  • 22 Welt CK, Chan JL, Bullen J , et al. Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med 2004; 351 (10) 987-997
  • 23 Gosman GG, Katcher HI, Legro RS. Obesity and the role of gut and adipose hormones in female reproduction. Hum Reprod Update 2006; 12 (5) 585-601
  • 24 Douglas CC, Gower BA, Darnell BE, Ovalle F, Oster RA, Azziz R. Role of diet in the treatment of polycystic ovary syndrome. Fertil Steril 2006; 85 (3) 679-688
  • 25 Katcher HI, Kunselman AR, Dmitrovic R , et al. Comparison of hormonal and metabolic markers after a high-fat, Western meal versus a low-fat, high-fiber meal in women with polycystic ovary syndrome. Fertil Steril 2009; 91 (4) 1175-1182
  • 26 Lobo RA, Goebelsmann U, Horton R. Evidence for the importance of peripheral tissue events in the development of hirsutism in polycystic ovary syndrome. J Clin Endocrinol Metab 1983; 57 (2) 393-397
  • 27 Roselli CE, Liu M, Hurn PD. Brain aromatization: classic roles and new perspectives. Semin Reprod Med 2009; 27 (3) 207-217
  • 28 Kaplowitz PB, Slora EJ, Wasserman RC, Pedlow SE, Herman-Giddens ME. Earlier onset of puberty in girls: relation to increased body mass index and race. Pediatrics 2001; 108 (2) 347-353
  • 29 Lobo RA, Granger L, Goebelsmann U, Mishell Jr DR. Elevations in unbound serum estradiol as a possible mechanism for inappropriate gonadotropin secretion in women with PCO. J Clin Endocrinol Metab 1981; 52 (1) 156-158
  • 30 Kaaks R, Lukanova A, Kurzer MS. Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review. Cancer Epidemiol Biomarkers Prev 2002; 11 (12) 1531-1543
  • 31 Pasquali R, Casimirri F, Venturoli S , et al. Body fat distribution has weight-independent effects on clinical, hormonal, and metabolic features of women with polycystic ovary syndrome. Metabolism 1994; 43 (6) 706-713
  • 32 Crave JC, Lejeune H, Brébant C, Baret C, Pugeat M. Differential effects of insulin and insulin-like growth factor I on the production of plasma steroid-binding globulins by human hepatoblastoma-derived (Hep G2) cells. J Clin Endocrinol Metab 1995; 80 (4) 1283-1289
  • 33 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 (1) 83-89
  • 34 Dmitrovic R, Katcher HI, Kunselman AR, Legro RS. Continuous glucose monitoring during pregnancy in women with polycystic ovary syndrome. Obstet Gynecol 2011; 118 (4) 878-885
  • 35 Morin-Papunen LC, Vauhkonen I, Koivunen RM, Ruokonen A, Martikainen HK, Tapanainen JS. Endocrine and metabolic effects of metformin versus ethinyl estradiol-cyproterone acetate in obese women with polycystic ovary syndrome: a randomized study. J Clin Endocrinol Metab 2000; 85 (9) 3161-3168
  • 36 Gosman GG, King WC, Schrope B , et al. Reproductive health of women electing bariatric surgery. Fertil Steril 2010; 94 (4) 1426-1431
  • 37 Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 1989; 38 (9) 1165-1174
  • 38 Dunaif A, Segal KR, Shelley DR, Green G, Dobrjansky A, Licholai T. Evidence for distinctive and intrinsic defects in insulin action in polycystic ovary syndrome. Diabetes 1992; 41 (10) 1257-1266
  • 39 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 (1) 165-169
  • 40 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 (1) 141-146
  • 41 Gambineri A, Pelusi C, Manicardi E , et al. Glucose intolerance in a large cohort of Mediterranean women with polycystic ovary syndrome: phenotype and associated factors. Diabetes 2004; 53 (9) 2353-2358
  • 42 Palmert MR, Gordon CM, Kartashov AI, Legro RS, Emans SJ, Dunaif A. Screening for abnormal glucose tolerance in adolescents with polycystic ovary syndrome. J Clin Endocrinol Metab 2002; 87 (3) 1017-1023
  • 43 Sinha R, Fisch G, Teague B , et al. Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. [See comments.] [Erratum appears in N Engl J Med 2002;346(22):1756.][ Note: Correction of dosage error in abstract.] N Engl J Med 2002; 346 (11) 802-810
  • 44 Wild RA, Carmina E, Diamanti-Kandarakis E , et al. Assessment of cardiovascular risk and prevention of cardiovascular disease in women with the polycystic ovary syndrome: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society. J Clin Endocrinol Metab 2010; 95 (5) 2038-2049
  • 45 Legro RS, Kunselman AR, Dunaif A. Prevalence and predictors of dyslipidemia in women with polycystic ovary syndrome. Am J Med 2001; 111 (8) 607-613
  • 46 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 (1) 48-53
  • 47 Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 2003; 348 (17) 1625-1638
  • 48 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
  • 49 Schmeler KM, Soliman PT, Sun CC, Slomovitz BM, Gershenson DM, Lu KH. Endometrial cancer in young, normal-weight women. Gynecol Oncol 2005; 99 (2) 388-392
  • 50 Secreto G, Zumoff B. Abnormal production of androgens in women with breast cancer. Anticancer Res 1994; 14 (5B) 2113-2117
  • 51 Legro RS, Chiu P, Kunselman AR, Bentley CM, Dodson WC, Dunaif A. Polycystic ovaries are common in women with hyperandrogenic chronic anovulation but do not predict metabolic or reproductive phenotype. J Clin Endocrinol Metab 2005; 90 (5) 2571-2579
  • 52 Solomon CG, Hu FB, Dunaif A , et al. Menstrual cycle irregularity and risk for future cardiovascular disease. J Clin Endocrinol Metab 2002; 87 (5) 2013-2017
  • 53 Solomon CG, Hu FB, Dunaif A , et al. Long or highly irregular menstrual cycles as a marker for risk of type 2 diabetes mellitus. JAMA 2001; 286 (19) 2421-2426
  • 54 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 oligoamenorrheic infertility. J Clin Endocrinol Metab 1999; 84 (5) 1617-1622
  • 55 Rausch ME, Legro RS, Barnhart HX , et al; Reproductive Medicine Network. Predictors of pregnancy in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2009; 94 (9) 3458-3466
  • 56 Imani B, Eijkemans MJ, de Jong FH , et al. Free androgen index and leptin are the most prominent endocrine predictors of ovarian response during clomiphene citrate induction of ovulation in normogonadotropic oligoamenorrheic infertility. J Clin Endocrinol Metab 2000; 85 (2) 676-682
  • 57 Boomsma CM, Eijkemans MJ, Hughes EG, Visser GH, Fauser BC, Macklon NS. A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome. Hum Reprod Update 2006; 12 (6) 673-683
  • 58 Vanky E, Stridsklev S, Heimstad R , et al. Metformin versus placebo from first trimester to delivery in polycystic ovary syndrome: a randomized, controlled multicenter study. J Clin Endocrinol Metab 2010; 95 (12) E448-E455
  • 59 Harrison CL, Lombard CB, Moran LJ, Teede HJ. Exercise therapy in polycystic ovary syndrome: a systematic review. Hum Reprod Update 2011; 17 (2) 171-183
  • 60 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 (6) 393-403
  • 61 Moran LJ, Noakes M, Clifton PM, Tomlinson L, Galletly C, Norman RJ. Dietary composition in restoring reproductive and metabolic physiology in overweight women with polycystic ovary syndrome. J Clin Endocrinol Metab 2003; 88 (2) 812-819
  • 62 Sacks FM, Bray GA, Carey VJ , et al. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med 2009; 360 (9) 859-873
  • 63 Thomson RL, Buckley JD, Noakes M, Clifton PM, Norman RJ, Brinkworth GD. The effect of a hypocaloric diet with and without exercise training on body composition, cardiometabolic risk profile, and reproductive function in overweight and obese women with polycystic ovary syndrome. J Clin Endocrinol Metab 2008; 93 (9) 3373-3380
  • 64 Hoeger K, Davidson K, Kochman L, Cherry T, Kopin L, Guzick DS. The impact of metformin, oral contraceptives, and lifestyle modification on polycystic ovary syndrome in obese adolescent women in two randomized, placebo-controlled clinical trials. J Clin Endocrinol Metab 2008; 93 (11) 4299-4306
  • 65 Ladson G, Dodson WC, Sweet SD , et al. The effects of metformin with lifestyle therapy in polycystic ovary syndrome: a randomized double-blind study. Fertil Steril 2011; 95 (3) 1059-1066 , e1–e7
  • 66 Moran LJ, Hutchison SK, Norman RJ, Teede HJ. Lifestyle changes in women with polycystic ovary syndrome. Cochrane Database Syst Rev 2011; 7 (7) CD007506
  • 67 Park MH, Kinra S, Ward KJ, White B, Viner RM. Metformin for obesity in children and adolescents: a systematic review. Diabetes Care 2009; 32 (9) 1743-1745
  • 68 Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev 2010; (1) CD003053
  • 69 Elkind-Hirsch K, Marrioneaux O, Bhushan M, Vernor D, Bhushan R. Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome. J Clin Endocrinol Metab 2008; 93 (7) 2670-2678
  • 70 Li Z, Maglione M, Tu W , et al. Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med 2005; 142 (7) 532-546
  • 71 Panidis D, Farmakiotis D, Rousso D, Kourtis A, Katsikis I, Krassas G. Obesity, weight loss, and the polycystic ovary syndrome: effect of treatment with diet and orlistat for 24 weeks on insulin resistance and androgen levels. Fertil Steril 2008; 89 (4) 899-906
  • 72 Jayagopal V, Kilpatrick ES, Holding S, Jennings PE, Atkin SL. Orlistat is as beneficial as metformin in the treatment of polycystic ovarian syndrome. J Clin Endocrinol Metab 2005; 90 (2) 729-733
  • 73 Sjöström L, Narbro K, Sjöström CD , et al; Swedish Obese Subjects Study. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007; 357 (8) 741-752
  • 74 Sjöström L, Lindroos AK, Peltonen M , et al; Swedish Obese Subjects Study Scientific Group. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med 2004; 351 (26) 2683-2693
  • 75 Escobar-Morreale HF, Botella-Carretero JI, Alvarez-Blasco F, Sancho J, San Millán 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
  • 76 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
  • 77 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 (11) 4006-4011
  • 78 Michelmore KF, Balen AH, Dunger DB, Vessey MP. Polycystic ovaries and associated clinical and biochemical features in young women. Clin Endocrinol (Oxf) 1999; 51 (6) 779-786
  • 79 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 (19) 2081-2086
  • 80 Chen X, Yang D, Mo Y, Li L, Chen Y, Huang Y. Prevalence of polycystic ovary syndrome in unselected women from southern China. Eur J Obstet Gynecol Reprod Biol 2008; 139 (1) 59-64
  • 81 Tehrani FR, Simbar M, Tohidi M, Hosseinpanah 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
  • 82 Dunaif A, Finegood DT. Beta-cell dysfunction independent of obesity and glucose intolerance in the polycystic ovary syndrome. J Clin Endocrinol Metab 1996; 81 (3) 942-947