Adiposity and metabolic dysfunction in polycystic ovary syndrome

Hormone Molecular Biology and Clinical Investigation

Volumn 21, Issue 2, 2015, Pages 107-116

  Sam, Susan ^a  

^a UNIVERSITY OF CHICAGO   (United States)

Author keywords

hyperandrogenism; inflammation; insulin resistance; lipolysis; visceral fat

Indexed keywords

ADIPOSE TISSUE; BODY COMPOSITION; BODY FAT DISTRIBUTION; DISEASE ASSOCIATION; DISEASE COURSE; DISEASE PREDISPOSITION; FEMALE; HUMAN; INFLAMMATION; INSULIN RESISTANCE; LIPOLYSIS; METABOLIC DISORDER; OBESITY; OVARY POLYCYSTIC DISEASE; PRIORITY JOURNAL; REVIEW; COMPLICATION; METABOLIC DISEASES; METABOLISM; PATHOLOGY;

ADIPOSITY; FEMALE; HUMANS; INFLAMMATION; INSULIN RESISTANCE; LIPOLYSIS; METABOLIC DISEASES; OVERWEIGHT; POLYCYSTIC OVARY SYNDROME;

EID: 84928649086     PISSN: 18681883     EISSN: 18681891     Source Type: Journal    
DOI: 10.1515/hmbci-2015-0008     Document Type: Review

References (150)

1. Sam S, Dunaif A. Polycystic ovary syndrome: syndrome XX? Trends Endocrinol Metab 2003;14:365-70.
2. Ehrmann DA. Polycystic ovary syndrome. N Engl J Med 2005;352:1223-36.
3. Luque-Ramirez M, Escobar-Morreale HF. Polycystic ovary syndrome as a paradigm for prehypertension, prediabetes, and preobesity. Curr Hypertens Rep 2014;16:500-10.
4. Randeva HS, Tan BK, Weickert MO, Lois K, Nestler JE, Sattar N, Lehnert H. Cardiometabolic aspects of the polycystic ovary syndrome. Endocr Rev 2012;33:812-41.
5. Lim SS, Norman RJ, Davies MJ, Moran LJ. The effect of obesity on polycystic ovary syndrome: a systematic review and meta-analy-sis. Obes Rev 2013;14:95-109.
6. Escobar-Morreale HF, San Millan JL. Abdominal adiposity and the polycystic ovary syndrome. Trends Endocrinol Metab 2007;18:266-72.
7. Barber TM, Franks S. Adipocyte biology in polycystic ovary syndrome. Mol Cell Endocrinol 2013;373:68-76.
8. 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;89:2745-9.
9. 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;85:2434-8.
10. Targher G, Solagna E, Tosi F, Castello R, Spiazzi G, Zoppini G, Muggeo M, Day CP, Moghetti P. Abnormal serum alanine aminotransferase levels are associated with impaired insulin sensitivity in young women with polycystic ovary syndrome. J Endocrinol Invest 2009;32:695-700.
11. Seow KM, Tsai YL, Hwang JL, Hsu WY, Ho LT, Juan CC. Omental adipose tissue overexpression of fatty acid transporter CD36 and decreased expression of hormone-sensitive lipase in insulin-resistant women with polycystic ovary syndrome. Hum Reprod 2009;24:1982-8.
12. Manneras-Holm L, Leonhardt H, Kullberg J, Jennische E, Oden A, Holm G, Hellstrom M, Lonn L, Olivecrona G, Stener-Victorin E, Lonn M. 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. J Clin Endocrinol Metab 2011;96:E304-11.
13. Huang ZH, Manickam B, Ryvkin V, Zhou XJ, Fantuzzi G, Mazzone T, Sam S. PCOS is associated with increased CD11c expression and crown-like structures in adipose tissue and increased central abdominal fat depots independent of obesity. J Clin Endocrinol Metab 2012;98:E17-24.
14. Pasquali R, Casimirri F, Cantobelli S, Labate AM, Venturoli S, Paradisi R, Zannarini L. Insulin and androgen relationships with abdominal body fat distribution in women with and without hyperandrogenism. Horm Res 1993;39:179-87.
15. 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;18:618-37.
16. 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;41:1257-66.
17. Horejsi R, Moller R, Rackl S, Giuliani A, Freytag U, Crailsheim K, Sudi K, Tafeit E. Android subcutaneous adipose tissue topography in lean and obese women suffering from PCOS: comparison with type 2 diabetic women. Am J Phys Anthropol 2004;124:275-81.
18. Evans DJ, Hoffmann RG, Kalkhoff RK, Kissebah AH. Relationship of androgenic activity to body fat topography, fat cell morphology, and metabolic aberrations in premenopausal women. J Clin Endocrinol Metab 1983;57:304-10.
19. Vague J. The degree of masculine differentiation of obesities: a factor determining predisposition to diabetes, atherosclerosis, gout, and uric calculous disease. Am J Clin Nutr 1956;4:20-34.
20. Bjorntorp P. Hyperandrogenicity in women-a prediabetic condition? J Intern Med 1993;234:579-83.
21. Wells JC. Sexual dimorphism of body composition. Best Pract Res Clin Endocrinol Metab 2007;21:415-30.
22. Lovejoy JC, Bray GA, Bourgeois MO, Macchiavelli R, Rood JC, Greeson C, Partington C. Exogenous androgens influence body composition and regional body fat distribution in obese postmenopausal women-a clinical research center study. J Clin Endocrinol Metab 1996;81:2198-203.
23. Elbers JM, Asscheman H, Seidell JC, Megens JA, Gooren LJ. Long-term testosterone administration increases visceral fat in female to male transsexuals. J Clin Endocrinol Metab 1997;82:2044-7.
24. Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel, SF; 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;91:4237-45.
25. Kosova G, Urbanek M. Genetics of the polycystic ovary syndrome. Mol Cell Endocrinol 2013;373:29-38.
26. Legro RS, Driscoll D, Strauss JF 3rd, Fox J, Dunaif A. Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome. Proc Natl Acad Sci USA 1998;95:14956-60.
27. Sam S, Legro RS, Bentley-Lewis R, Dunaif A. Dyslipidemia and metabolic syndrome in the sisters of women with polycystic ovary syndrome. J Clin Endocrinol Metab 2005;90:4797-802.
28. Sam S, Legro RS, Essah PA, Apridonidze T, Dunaif A. Evidence for metabolic and reproductive phenotypes in mothers of women with polycystic ovary syndrome. Proc Natl Acad Sci USA 2006;103:7030-5.
29. Legro RS, Kunselman AR, Demers L, Wang SC, Bentley-Lewis R, Dunaif A. Elevated dehydroepiandrosterone sulfate levels as the reproductive phenotype in the brothers of women with polycys-tic ovary syndrome. J Clin Endocrinol Metab 2002;87:2134-8.
30. Sam S, Coviello AD, Sung YA, Legro RS, Dunaif A. Metabolic phenotype in the brothers of women with polycystic ovary syndrome. Diabetes Care 2008;31:1237-41.
31. Corton M, Botella-Carretero JI, Lopez JA, Camafeita E, San Millan JL, Escobar-Morreale HF, Peral B. Proteomic analysis of human omental adipose tissue in the polycystic ovary syndrome using two-dimensional difference gel electrophoresis and mass spectrometry. Hum Reprod 2008;23:651-61.
32. Corton M, Botella-Carretero JI, Benguria A, Villuendas G, Zabal-los A, San Millan JL, Escobar-Morreale HF, Peral B. Differential gene expression profile in omental adipose tissue in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2007;92:328-37.
33. Nestler JE, Jakubowicz DJ. Decreases in ovarian cytochrome P450c17 α activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. N Engl J Med 1996;335:617-23.
34. Mai K, Bobbert T, Reinecke F, Andres J, Maser-Gluth C, Wudy SA, Mohlig M, Weickert MO, Hartmann MF, Schulte HM. Intravenous lipid and heparin infusion-induced elevation in free fatty acids and triglycerides modifies circulating androgen levels in women: a randomized, controlled trial. J Clin Endocrinol Metab 2008;93:3900-6.
35. Bellanger S, Battista MC, Fink GD, Baillargeon JP. Saturated fatty acid exposure induces androgen overproduction in bovine adrenal cells. Steroids 2012;77:347-53.
36. Despres JP, Lemieux I, Bergeron J, Pibarot P, Mathieu P, Larose E, Rodes-Cabau J, Bertrand OF, Poirier P. Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol 2008;28:1039-49.
37. Fox CS, Massaro JM, Hoffmann U, Pou KM, Maurovich-Horvat P, Liu CY, Vasan RS, Murabito JM, Meigs JB, Cupples LA, D'Agostino RB Sr, O'Donnell CJ. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation 2007;116:39-48.
38. Fox CS, Hwang SJ, Massaro JM, Lieb K, Vasan RS, O'Donnell CJ, Hoffmann U. Relation of subcutaneous and visceral adipose tissue to coronary and abdominal aortic calcium (from the Framingham Heart Study). Am J Cardiol 2009;104:543-7.
39. Bray GA, Jablonski KA, Fujimoto WY, Barrett-Connor E, Haffner S, Hanson RL, Hill JO, Hubbard V, Kriska A, Stamm E, Pi-Sunyer FX. Relation of central adiposity and body mass index to the development of diabetes in the Diabetes Prevention Program. Am J Clin Nutr 2008;87:1212-8.
40. Sam S, Haffner S, Davidson MH, D'Agostino RB Sr, Feinstein S, Kondos G, Perez A, Mazzone T. Relation of abdominal fat depots to systemic markers of inflammation in type 2 diabetes. Diabetes Care 2009;32:932-7.
41. Sam S, Haffner S, Davidson MH, D'Agostino RB Sr, Feinstein S, Kondos G, Perez A, Mazzone T. Relationship of abdominal visceral and subcutaneous adipose tissue with lipoprotein particle number and size in type 2 diabetes. Diabetes 2008;57:2022-7.
42. Sam S, Haffner S, Davidson MH, D'Agostino RB Sr, Feinstein S, Kondos G, Perez A, Mazzone T. Hypertriglyceridemic waist phenotype predicts increased visceral fat in subjects with type 2 diabetes. Diabetes Care 2009;32:1916-20.
43. Jensen MD. Role of body fat distribution and the metabolic complications of obesity. J Clin Endocrinol Metab 2008;93:S57-63.
44. Arner P. Not all fat is alike. Lancet 1998;351:1301-2.
45. Rebrin K, Steil GM, Mittelman SD, Bergman RN. Causal linkage between insulin suppression of lipolysis and suppression of liver glucose output in dogs. J Clin Invest 1996;98:741-9.
46. Bergman RN, Ader M. Free fatty acids and pathogenesis of type 2 diabetes mellitus. Trends Endocrinol Metab 2000;11:351-6.
47. Fried SK, Bunkin DA, Greenberg AS. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J Clin Endocrinol Metab 1998;83:847-50.
48. Bruun JM, Lihn AS, Pedersen SB, Richelsen B. Monocyte chem-oattractant protein-1 release is higher in visceral than subcutaneous human adipose tissue (AT): implication of macrophages resident in the AT. J Clin Endocrinol Metab 2005;90:2282-9.
49. Alessi MC, Peiretti F, Morange P, Henry M, Nalbone G, Juhan-Vague I. Production of plasminogen activator inhibitor 1 by human adipose tissue: possible link between visceral fat accumulation and vascular disease. Diabetes 1997;46:860-7.
50. Festa A, D'Agostino R Jr, Williams K, Karter AJ, Mayer-Davis EJ, Tracy RP, Haffner SM. The relation of body fat mass and distribution to markers of chronic inflammation. Int J Obes Relat Metab Disord 2001;25:1407-15.
51. Lemieux I, Pascot A, Prud'homme D, Almeras N, Bogaty P, Nadeau A, Bergeron J, Despres JP. Elevated C-reactive protein: another component of the atherothrombotic profile of abdominal obesity. Arterioscler Thromb Vasc Biol 2001;21:961-7.
52. Lihn AS, Bruun JM, He G, Pedersen SB, Jensen PF, Richelsen B. Lower expression of adiponectin mRNA in visceral adipose tissue in lean and obese subjects. Mol Cell Endocrinol 2004;219:9-15.
53. Fabbrini E, Magko F, Mohammed BS, Pietka T, Abumrad NA, Patterson BW, Okunade A, Klein S. Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity. Proc Natl Acad Sci USA 2009;106:15430-5.
54. Aydogdu A, Tasci I, Kucukerdonmez O, Tapan S, Aydogdu S, Aydogan U, Sonmez A, Yazici M, Azal O. Increase in subcutaneous adipose tissue and fat free mass in women with polycystic ovary syndrome is related to impaired insulin sensitivity. Gynecol Endocrinol 2013;29:152-5.
55. Borruel S, Fernandez-Duran E, Alpanes M, Marti D, Alvarez-Blasco F, Luque-Ramirez M, Escobar-Morreale HF. Global adiposity and thickness of intraperitoneal and mesenteric adipose tissue depots are increased in women with polycystic ovary syndrome (PCOS). J Clin Endocrinol Metab 2013;98:1254-63.
56. Jones H, Sprung VS, Pugh CJ, Daousi C, Irwin A, Aziz N, Adams VL, Thomas EL, Bell JD, Kemp GJ, Cuthbertson DJ. Polycystic ovary syndrome with hyperandrogenism is characterized by an increased risk of hepatic steatosis compared to nonhyperandrogenic PCOS phenotypes and healthy controls, independent of obesity and insulin resistance. J Clin Endocrinol Metab 2012;97:3709-16.
57. Battaglia C, Battaglia B, Mancini F, Paradisi R, Fabbri R, Ven-turoli S. Ultrasonographic extended-view technique for evaluation of abdominal fat distribution in lean women with polycystic ovary syndrome. Acta Obstet Gynecol Scand 2011;90:600-8.
58. Carmina E, Bucchieri S, Esposito A, Del Puente A, Mansueto P, Orio F, Di Fede G, Rini G. Abdominal fat quantity and distribution in women with polycystic ovary syndrome and extent of its relation to insulin resistance. J Clin Endocrinol Metab 2007;92:2500-5.
59. Kirchengast S, Huber J. Body composition characteristics and body fat distribution in lean women with polycystic ovary syndrome. Hum Reprod 2001;16:1255-60.
60. Hutchison SK, Stepto NK, Harrison CL, Moran LJ, Strauss BJ, Teede HJ. Effects of exercise on insulin resistance and body composition in overweight and obese women with and without polycystic ovary syndrome. J Clin Endocrinol Metab 2011;96:E48-56.
61. Barber TM, Golding SJ, Alvey C, Wass JA, Karpe F, Franks S, McCarthy MI. Global adiposity rather than abnormal regional fat distribution characterizes women with polycystic ovary syndrome. J Clin Endocrinol Metab 2008; 93:999-1004.
62. Oh JY, Lee JA, Lee H, Oh JY, Sung YA, Chung H. Serum C-reactive protein levels in normal-weight polycystic ovary syndrome. Korean J Intern Med 2009;24:350-5.
63. Dolfing JG, Stassen CM, van Haard PM, Wolffenbuttel BH, Schweitzer DH. Comparison of MRI-assessed body fat content between lean women with polycystic ovary syndrome (PCOS) and matched controls: less visceral fat with PCOS. Hum Reprod 2011;26:1495-500.
64. Sun K, Kusminski CM, Scherer PE. Adipose tissue remodeling and obesity. J Clin Invest 2011;121:2094-101.
65. Villa J, Pratley RE. Adipose tissue dysfunction in polycystic ovary syndrome. Curr Diab Rep 2011;11:179-84.
66. Deligeoroglou E, Vrachnis N, Athanasopoulos N, Iliodromiti Z, Sifakis S, Iliodromiti S, Siristatidis C, Creatsas G. Mediators of chronic inflammation in polycystic ovarian syndrome. Gynecol Endocrinol 2012;28:974-8.
67. Diamanti-Kandarakis E. Role of obesity and adiposity in polycys-tic ovary syndrome. Int J Obes (Lond) 2007;(31 Suppl 2):S8-13; discussion S31-2.
68. Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in poly-cystic ovary syndrome. Diabetes 1989;38:1165-74.
69. Ciaraldi TP, Aroda V, Mudaliar S, Chang RJ, Henry RR. Polycystic ovary syndrome is associated with tissue-specific differences in insulin resistance. J Clin Endocrinol Metab 2009;94:157-63.
70. Ciaraldi TP, el-Roeiy A, Madar Z, Reichart D, Olefsky JM, Yen SS. Cellular mechanisms of insulin resistance in polycystic ovarian syndrome. J Clin Endocrinol Metab 1992;75:577-83.
71. Ciaraldi TP, Morales AJ, Hickman MG, Odom-Ford R, Olefsky JM, Yen SS. Cellular insulin resistance in adipocytes from obese polycystic ovary syndrome subjects involves adenosine modulation of insulin sensitivity. J Clin Endocrinol Metab 1997;82:1421-5.
72. Marsden PJ, Murdoch A, Taylor R. Severe impairment of insulin action in adipocytes from amenorrheic subjects with polycystic ovary syndrome. Metabolism 1994;43:1536-42.
73. Rosenbaum D, Haber RS, Dunaif A. Insulin resistance in poly-cystic ovary syndrome: decreased expression of GLUT-4 glucose transporters in adipocytes. Am J Physiol 1993;264:E197-202.
74. Chen YH, Heneidi S, Lee JM, Layman LC, Stepp DW, Gamboa GM, Chen BS, Chazenbalk G, Azziz R. miRNA-93 inhibits GLUT4 and is overexpressed in adipose tissue of polycystic ovary syndrome patients and women with insulin resistance. Diabetes 2013;62:2278-86.
75. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004;89:2548-56.
76. Lumeng CN, Saltiel AR. Inflammatory links between obesity and metabolic disease. J Clin Invest 2011;121:2111-7.
77. Schenk S, Saberi M, Olefsky JM. Insulin sensitivity: modulation by nutrients and inflammation. J Clin Invest 2008;118: 2992-3002.
78. Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Annu Rev Immunol 2011;29:415-45.
79. Mathieu P, Poirier P, Pibarot P, Lemieux I, Despres JP. Visceral obesity: the link among inflammation, hypertension, and cardiovascular disease. Hypertension 2009;53:577-84.
80. Sam S, Mazzone T. Adipose tissue changes in obesity and the impact on metabolic function. Transl Res 2014;164:284-92.
81. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003;112:1821-30.
82. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003;112:1796-808.
83. Oh DY, Morinaga H, Talukdar S, Bae EJ, Olefsky JM. Increased macrophage migration into adipose tissue in obese mice. Diabetes 2012;61:346-54.
84. Patsouris D, Li PP, Thapar D, Chapman J, Olefsky JM, Neels JG. Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals. Cell Metab 2008;8:301-9.
85. Cancello R, Henegar C, Viguerie N, Taleb S, Poitou C, Rouault C, Coupaye M, Pelloux V, Hugol D, Bouillot JL, Bouloumie A, Barbatelli G, Cinti S, Svensson PA, Barsh GS, Zucker JD, Basdevant A, Langin D, Clement K. Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes 2005;54:2277-86.
86. Wentworth JM, Naselli G, Brown WA, Doyle L, Phipson B, Smyth GK, Wabitsch M, O'Brien PE, Harrison LC. Pro-inflammatory CD11c+CD206+ adipose tissue macrophages are associated with insulin resistance in human obesity. Diabetes 2010;59:1648-56.
87. Feinstein R, Kanety H, Papa MZ, Lunenfeld B, Karasik A. Tumor necrosis factor-α suppresses insulin-induced tyrosine phos-phorylation of insulin receptor and its substrates. J Biol Chem 1993;268:26055-8.
88. Tao T, Li S, Zhao A, Zhang Y, Liu W. Expression of the CD11c gene in subcutaneous adipose tissue is associated with cytokine level and insulin resistance in women with polycystic ovary syndrome. Eur J Endocrinol 2012;167:705-13.
89. Manneras-Holm L, Benrick A, Stener-Victorin E. Gene expression in subcutaneous adipose tissue differs in women with polycystic ovary syndrome and controls matched pair-wise for age, body weight, and body mass index. Adipocyte 2014;3:190-6.
90. Toulis KA, Goulis DG, Farmakiotis D, Georgopoulos NA, Katsikis I, Tarlatzis BC, Papadimas I, Panidis D. Adiponectin levels in women with polycystic ovary syndrome: a systematic review and a meta-analysis. Hum Reprod Update 2009;15:297-307.
91. Chazenbalk G, Trivax BS, Yildiz BO, Bertolotto C, Mathur R, Heneidi S, Azziz R. Regulation of adiponectin secretion by adipocytes in the polycystic ovary syndrome: role of tumor necrosis factor-{α}. J Clin Endocrinol Metab 2010;95:935-42.
92. Mlinar B, Marc J. New insights into adipose tissue dysfunction in insulin resistance. Clin Chem Lab Med 2011;49:1925-35.
93. Wang L, Li S, Zhao A, Tao T, Mao X, Zhang P, Liu W. The expression of sex steroid synthesis and inactivation enzymes in subcutaneous adipose tissue of PCOS patients. J Steroid Biochem Mol Biol 2012;132:120-6.
94. Pedersen SB, Fuglsig S, Sjogren P, Richelsen B. Identification of steroid receptors in human adipose tissue. Eur J Clin Invest 1996;26:1051-6.
95. Corbould A. Chronic testosterone treatment induces selective insulin resistance in subcutaneous adipocytes of women. J Endocrinol 2007; 192:585-94.
96. Corbould A. Effects of spironolactone on glucose transport and interleukin-6 secretion in adipose cells of women. Horm Metab Res 2007;39:915-8.
97. Kovacs P, Stumvoll M. Fatty acids and insulin resistance in muscle and liver. Best Pract Res Clin Endocrinol Metab 2005;19:625-35.
98. Ek I, Arner P, Bergqvist A, Carlstrom K, Wahrenberg H. Impaired adipocyte lipolysis in nonobese women with the polycystic ovary syndrome: a possible link to insulin resistance? J Clin Endocrinol Metab 1997;82:1147-53.
99. Faulds G, Ryden M, Ek I, Wahrenberg H, Arner P. Mechanisms behind lipolytic catecholamine resistance of subcutaneous fat cells in the polycystic ovarian syndrome. J Clin Endocrinol Metab 2003;88:2269-73.
100. Arner P. Efects of testosterone on fat cell lipolysis. Species diferences and possible role in polycystic ovarian syndrome. Biochimie 2005;87:39-43.
101. Dicker A, Ryden M, Naslund E, Muehlen IE, Wiren M, Lafontan M, Arner P. Efect of testosterone on lipolysis in human pre-adipo-cytes from diferent fat depots. Diabetologia 2004;47:420-8.
102. Ek I, Arner P, Ryden M, Holm C, Thorne A, Hofstedt J, Wahren-berg H. A unique defect in the regulation of visceral fat cell lipolysis in the polycystic ovary syndrome as an early link to insulin resistance. Diabetes 2002;51:484-92.
103. Trottier A, Battista MC, Geller DH, Moreau B, Carpentier AC, Simoneau-Roy J, Baillargeon JP. Adipose tissue insulin resistance in peripubertal girls with frst-degree family history of polycystic ovary syndrome. Fertil Steril 2012;98:1627-34.
104. Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev 2012;33:981-1030.
105. Lord J, Thomas R, Fox B, Acharya U, Wilkin T. The central issue? Visceral fat mass is a good marker of insulin resistance and metabolic disturbance in women with polycystic ovary syndrome. Brit J Obstet Gynecol 2006;113:1203-9.
106. Cascella T, Palomba S, De Sio I, Manguso F, Giallauria F, De Simone B, Tafuri D, Lombardi G, Colao A, Orio F. Visceral fat is associated with cardiovascular risk in women with polycystic ovary syndrome. Hum Reprod 2008;23:153-9.
107. Dunaif A, Finegood DT. β-Cell dysfunction independent of obesity and glucose intolerance in the polycystic ovary syndrome. J Clin Endocrinol Metab 1996;81:942-7.
108. Ehrmann DA, Sturis J, Byrne MM, Karrison T, Rosenfeld RL, Polonsky KS. Insulin secretory defects in polycystic ovary syndrome. Relationship to insulin sensitivity and family history of non-insulin-dependent diabetes mellitus. J Clin Invest 1995;96:520-7.
109. 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 afected women. J Clin Endocrinol Metab 1999;84:165-9.
110. Ehrmann DA, Barnes RB, Rosenfeld RL, Cavaghan MK, Imperial J. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care 1999;22:141-6.
111. Vrbikova J, Hill M, Fanta M. The utility of fasting plasma glucose to identify impaired glucose metabolism in women with polycystic ovary syndrome. Gynecol Endocrinol 2014;30: 664-6.
112. Salley KE, Wickham EP, Cheang KI, Essah PA, Karjane NW, Nestler JE. Glucose intolerance in polycystic ovary syndrome-a position statement of the Androgen Excess Society. J Clin Endocrinol Metab 2007;92:4546-56.
113. Wild RA, Carmina E, Diamanti-Kandarakis E, Dokras A, Escobar-Morreale HF, Futterweit W, Lobo R, Norman RJ, Talbott E, Dumesic DA. 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;95:2038-49.
114. Conway G, Dewailly D, Diamanti-Kandarakis E, Escobar-Morre-ale HF, Franks S, Gambineri A, Kelestimur F, Macut D, Micic D, Pasquali R, Pfeifer M, Pignatelli D, Pugeat M, Yildiz B. The poly-cystic ovary syndrome: a position statement from the European Society of Endocrinology. Eur J Endocrinol 2014;171:P1-29.
115. Conway GS, Agrawal R, Betteridge DJ, Jacobs HS. Risk factors for coronary artery disease in lean and obese women with the poly-cystic ovary syndrome. Clin Endocrinol (Oxf) 1992;37:119-25.
116. Wild RA, Painter PC, Coulson PB, Carruth KB, Ranney GB. Lipo-protein lipid concentrations and cardiovascular risk in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1985;61:946-51.
117. Dejager S, Pichard C, Giral P, Bruckert E, Federspield MC, Beu-cler I, Turpin G. Smaller LDL particle size in women with poly-cystic ovary syndrome compared to controls. Clin Endocrinol (Oxf) 2001;54:455-62.
118. Talbott E, Clerici A, Berga SL, Kuller L, Guzick D, Detre K, Daniels T, Engberg RA. Adverse lipid and coronary heart disease risk profles in young women with polycystic ovary syndrome: results of a case-control study. J Clin Epidemiol 1998;51:415-22.
119. Legro RS, Kunselman AR, Dunaif A. Prevalence and predictors of dyslipidemia in women with polycystic ovary syndrome. Am J Med 2001;111:607-13.
120. Berneis K, Rizzo M, Lazzarini V, Fruzzetti F, Carmina E. Atherogenic lipoprotein phenotype and low-density lipoproteins size and subclasses in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2007;92:186-9.
121. Diamanti-Kandarakis E, Papavassiliou AG, Kandarakis SA, Chrousos GP. Pathophysiology and types of dyslipidemia in PCOS. Trends Endocrinol Metab 2007;18:280-5.
122. Sidhwani S, Scoccia B, Sunghay S, Stephens-Archer CN, Maz-zone T, Sam S. PCOS is associated with atherogenic changes in lipoprotein particle number and size independent of body weight. Clin Endocrinol (Oxf) 2011;75:76-82.
123. Lo JC, Feigenbaum SL, Yang J, Pressman AR, Selby JV, Go AS. Epidemiology and adverse cardiovascular risk profle of diagnosed polycystic ovary syndrome. J Clin Endocrinol Metab 2006;91:1357-63.
124. Ehrmann DA, Liljenquist DR, Kasza K, Azziz R, Legro RS, Ghazzi MN. Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2006;91:48-53.
125. 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: 1929-35.
126. Hu WH, Qiao J, Wang LN, Tong J. Clinical features of the metabolic syndrome in patients with polycystic ovary syndrome. Beijing Da Xue Xue Bao 2010;42:159-63.
127. Weerakiet S, Bunnag P, Phakdeekitcharoen B, Wansumrith S, Chanprasertyothin S, Jultanmas R, Thakkinstian A. Prevalence of the metabolic syndrome in Asian women with polycystic ovary syndrome: using the International Diabetes Federation criteria. Gynecol Endocrinol 2007;23:153-60.
128. Hahn S, Tan S, Sack S, Kimmig R, Quadbeck B, Mann K, Janssen OE. Prevalence of the metabolic syndrome in German women with polycystic ovary syndrome. Exp Clin Endocrinol Diabetes 2007;115:130-5.
129. Markou A, Androulakis II, Mourmouris C, Tsikkini A, Samara C, Sougioultzis S, Piaditis G, Kaltsas G. Hepatic steatosis in young lean insulin resistant women with polycystic ovary syndrome. Fertil Steril 2010;93:1220-6.
130. Economou F, Xyrafs X, Livadas S, Androulakis II, Argyrako-poulou G, Christakou CD, Kandaraki E, Palioura E, Diamanti-Kandarakis E. In overweight/obese but not in normal-weight women, polycystic ovary syndrome is associated with elevated liver enzymes compared to controls. Hormones 2009;8:199-206.
131. Tasali E, Van Cauter E, Ehrmann DA. Relationships between sleep disordered breathing and glucose metabolism in polycys-tic ovary syndrome. J Clin Endocrinol Metab 2006;91:36-42.
132. Mokhlesi B, Scoccia B, Mazzone T, Sam S. Risk of obstructive sleep apnea in obese and nonobese women with polycystic ovary syndrome and healthy reproductively normal women. Fertil Steril 2012;97:786-91.
133. Fogel RB, Malhotra A, Pillar G, Pittman SD, Dunaif A, White DP. Increased prevalence of obstructive sleep apnea syndrome in obese women with polycystic ovary syndrome. J Clin Endo-crinol Metab 2001;86:1175-80.
134. Tasali E, Van Cauter E, Hofman L, Ehrmann DA. Impact of obstructive sleep apnea on insulin resistance and glucose intolerance in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2008;93:3878-84.
135. Sprung VS, Atkinson G, Cuthbertson DJ, Pugh CJ, Aziz N, Green DJ, Cable NT, Jones H. Endothelial function measured using flow-mediated dilation in polycystic ovary syndrome: a meta-analysis of the observational studies. Clin Endocrinol (Oxf) 2013;78:438-46.
136. Moran LJ, Pasquali R, Teede HJ, Hoeger KM, Norman RJ. Treatment of obesity in polycystic ovary syndrome: a position statement of the Androgen Excess and Polycystic Ovary Syndrome Society. Fertil Steril 2009;92:1966-82.
137. Moran LJ, Hutchison SK, Norman RJ, Teede HJ. Lifestyle changes in women with polycystic ovary syndrome. Cochrane Database Syst Rev 2011;CD007506.
138. Pasquali R, Gambineri A, Cavazza C, Ibarra Gasparini D, Ciampaglia W, Cognigni GE, Pagotto U. Heterogeneity in the responsiveness to long-term lifestyle intervention and predictability in obese women with polycystic ovary syndrome. Eur J Endocrinol 2011;164:53-60.
139. Pasquali R, Antenucci D, Casimirri F, Venturoli S, Paradisi R, Fabbri R, Balestra V, Melchionda N, Barbara L. Clinical and hormonal characteristics of obese amenorrheic hyperandrogenic women before and afer weight loss. J Clin Endocrinol Metab 1989;68:173-9.
140. Jakubowicz DJ, Nestler JE. 17α-Hydroxyprogesterone responses to leuprolide and serum androgens in obese women with and without polycystic ovary syndrome ofer dietary weight loss. J Clin Endocrinol Metab 1997;82:556-60.
141. Pasquali R, Gambineri A, Biscotti D, Vicennati V, Gagliardi L, Colitta D, Fiorini S, Cognigni GE, Filicori M, Morselli-Labate AM. Efect of long-term treatment with metformin added to hypoca-loric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome. J Clin Endocrinol Metab 2000;85:2767-74.
142. Gambineri A, Pelusi C, Genghini S, Morselli-Labate AM, Cacciari M, Pagotto U, Pasquali R. Efect of flutamide and met-formin administered alone or in combination in dieting obese women with polycystic ovary syndrome. Clin Endocrinol (Oxf) 2004;60:241-9.
143. Hoeger KM, Kochman L, Wixom N, Craig K, Miller RK, Guzick DS. A randomized, 48-week, placebo-controlled trial of intensive lifestyle modifcation and/or metformin therapy in overweight women with polycystic ovary syndrome: a pilot study. Fertil Steril 2004;82:421-9.
144. Gambineri A, Patton L, Vaccina A, Cacciari M, Morselli-Labate AM, Cavazza C, Pagotto U, Pasquali R. Treatment with flutamide, metformin, and their combination added to a hypocaloric diet in overweight-obese women with polycystic ovary syndrome: a randomized, 12-month, placebo-controlled study. J Clin Endocrinol Metab 2006;91:3970-80.
145. Moran LJ, Ko H, Misso M, Marsh K, Noakes M, Talbot M, Frearson M, Thondan M, Stepto N, Teede HJ. Dietary composition in the treatment of polycystic ovary syndrome: a systematic review to inform evidence-based guidelines. J Acad Nutr Diet 2013;113:520-45.
146. Gambineri A, Pelusi C, Manicardi E, Vicennati V, Cacciari M, Morselli-Labate AM, Pagotto U, Pasquali R. Glucose intolerance in a large cohort of Mediterranean women with polycystic ovary syndrome: phenotype and associated factors. Diabetes 2004;53:2353-8.
147. Jayagopal V, Kilpatrick ES, Holding S, Jennings PE, Atkin SL. Orlistat is as benefcial as metformin in the treatment of polycystic ovarian syndrome. J Clin Endocrinol Metab 2005;90:729-33.
148. Escobar-Morreale HF, Botella-Carretero JI, Alvarez-Blasco F, Sancho J, San Millan JL. The polycystic ovary syndrome associated with morbid obesity may resolve afer weight loss induced by bariatric surgery. J Clin Endocrinol Metab 2005;90:6364-9.
149. Harrison CL, Lombard CB, Moran LJ, Teede HJ. Exercise therapy in polycystic ovary syndrome: a systematic review. Hum Reprod Update 2011;17:171-83.
150. Palomba S, Giallauria F, Falbo A, Russo T, Oppedisano R, Tolino A, Colao A, Vigorito C, Zullo F, Orio F. Structured exercise training programme versus hypocaloric hyperproteic diet in obese polycystic ovary syndrome patients with anovulatory infertility: a 24-week pilot study. Hum Reprod 2008;23:642-50.