1.Dunaif, A (1997) Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 18, 774–800.
2.Hamilton-Fairley, D & Taylor, A (2003) Anovulation. BMJ 327, 546–549.
3.Cronin, L, Guyatt, G, Griffith, L et al. (1998) Development of a health-related quality-of-life questionnaire (PCOSQ) for women with polycystic ovary syndrome (PCOS). J Clin Endocrinol Metab 83, 1976–1987.
4.Barnard, L, Ferriday, D, Guenther, N et al. (2007) Quality of life and psychological well being in polycystic ovary syndrome. Hum Reprod 22, 2279–2286.
5.Burghen, GA, Givens, JR & Kitbachi, AE (1980) Correlation of hyperandrogenism with hyperinsulinism in polycystic ovarian disease. J Clin Endocrinol Metab 50, 113–116.
6.Dunaif, A, Segal, KR, Futterweit, W et al. (1989) Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 38, 1165–1174.
7.Jonard, S & Dewailly, D (2004) The follicular excess in polycystic ovaries, due to intra-ovarian hyperandrogenism, may be the main culprit for the follicular arrest. Hum Reprod Update 10, 107–117.
8.Westerveld, HE, Hoogendoorn, M, De Jong, AW et al. (2008) Cardiometabolic abnormalities in the polycystic ovary syndrome: pharmacotherapeutic insights. Pharmacol Ther 119, 223–241.
9.Phelan, N, O'Connor, A, Kyaw Tun, T et al. (2010) Lipoprotein subclass patterns in women with PCOS compared to equally insulin resistant women without PCOS. J Clin Endocrinol Metab (In the Press).
10.Velasquez, ME, Bellabarba, GA, Mendoza, S et al. (2000) Postprandial triglyceride response in patients with polycystic ovary syndrome: relationship with waist-to-hip ratio and insulin. Fertil Steril 74, 1159–1163.
11.Bahceci, M, Aydemir, M & Tuzcu, A (2007) Effects of oral fat and glucose tolerance test on serum lipid profile, apolipoprotein, and CRP concentration, and insulin resistance in patients with polycystic ovary syndrome. Fertil Steril 87, 1363–1368.
12.Stampfer, MJ, Krauss, RM, Ma, J et al. (1996) A prospective study of triglyceride level, low-density lipoprotein particle diameter, and risk of myocardial infarction. JAMA 276, 882–888.
13.Bansal, S, Buring, JE, Rifia, N et al. (2007) Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA 298, 309–316.
14.Talbott, EO, Guzick, DS, Sutton-Tyrrell, K et al. (2000) Evidence for association between polycystic ovary syndrome and premature carotid atherosclerosis in middle-aged women. Arterioscler Thromb Vasc Biol 20, 2414–2421.
15.Barber, TM, McCarthy, MI, Wass, JA et al. (2006) Obesity and polycystic ovary syndrome. Clin Endocrinol (Oxf) 65, 137–145.
16.Gambineri, A, Pelusi, C, Vicenatti, V et al. (2002) Obesity and the polycystic ovary syndrome. Int J Obes Relat Metab Disord 26, 883–896.
17.Kirchengast, S & Huber, J (2001) Body composition characteristics and body fat distribution in lean women with polycystic ovary syndrome. Hum Reprod 16, 1255–1260.
18.Cascella, T, Palomba, S, De Sio, I et al. (2008) Visceral fat is associated with cardiovascular risk in women with polycystic ovary syndrome. Hum Reprod 23, 153–159.
19.Yildrim, B, Sabir, N & Kaleli, B (2003) Relation of intra-abdominal fat distribution to metabolic disorders in nonobese patients with polycystic ovary syndrome. Fertil Steril 79, 1358–1364.
20.Carmina, E, Orio, F, Palomba, S et al. (2005) Evidence for altered adipocyte function in polycystic ovary syndrome. Eur J Endocrinol 152, 389–394.
21.Barber, TM, Hazell, M, Christodoulides, C et al. (2008) Serum levels of retinol-binding protein 4 and adiponectin in women with polycystic ovary syndrome: associations with visceral fat but no evidence for fat mass-independent effects on pathogenesis in this condition. J Clin Endocrinol Metab 93, 2859–2865.
22.O'Connor, A, Phelan, N, Tun, TK et al. (2010). High-molecular-weight adiponectin is selectively reduced in women with polycystic ovary syndrome independent of body mass index and severity of insulin resistance. Clin Endocrinol Metab 95, 1378–1385.
23.Faulds, G, Ryden, M, Ek, I et al. (2003) Mechanisms behind lipolytic catecholamine resistance of subcutaneous fat cells in the polycystic ovarian syndrome. J Clin Endocrinol Metab 88, 2269–2273.
24.Corton, M, Botella-Carreterro, JI, Benguria, A et al. (2007) Differential gene expression profile in omental adipose tissue in women with polycystic ovary syndrome. J Clin Endocrinol Metab 92, 328–337.
25.Montague, CT & O'Rahilly, S (2000) The perils of portliness: causes and consequences of visceral adiposity. Diabetes 49, 883–888.
26.Goodpaster, BH, Thaete, FL, Simoneau, JA et al. (1997) Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat. Diabetes 46, 1579–1585.
27.Abate, N, Garg, A, Peshock, RM et al. (1995) Relationships of generalized and regional adiposity to insulin sensitivity in men. J Clin Invest 96, 88–98.
28.Gilling-Smith, C, Willis, DS, Beard, RW et al. (1994) Hypersecretion of androstenedione by isolated thecal cells from polycystic ovaries. J Clin Endocrinol Metab 79, 1158–1165.
29.Nelson, VL, Legro, RS, Strauss, JF III et al. (1999) Augmented androgen production is a stable steroidogenic phenotype of propagated theca cells from polycystic ovaries. Mol Endocrinol 13, 946–957.
30.Wickenheisser, JK, Nelson-DeGrave, VL, Hendricks, KL et al. (2005) Retinoids and retinol differentially regulate steroid biosynthesis in ovarian theca cells isolated from normal cycling women and women with polycystic ovary syndrome. J Clin Endocrinol Metab, 90 4858–4865.
31.Wood, JR, Nelson, VL, Ho, C et al. (2003) The molecular phenotype of polycystic ovary syndrome (PCOS) theca cells and new candidate PCOS genes defined by microarray analysis. J Biol Chem 278, 26380–26390.
32.Nelson-DeGrave, VL, Wickenheisser, JK, Hendricks, KL et al. (2005) Alterations in mitogen-activated protein kinase kinase and extracellular regulated kinase signaling in theca cells contribute to excessive androgen production in polycystic ovary syndrome. Mol Endocrinol 19, 379–390.
33.Wickensheisser, JK, Nelson-DeGrave, VL & McAllister, JM (2005) Dysregulation of cytochrome P450 17alpha-hydroxylase messenger ribonucleic acid stability in theca cells isolated from women with polycystic ovary syndrome. J Clin Endocrinol Metab 90, 1720–1727.
34.Abbott, DH, Padmanabhan, V & Dumesic, DA (2006) Contributions of androgen and estrogen to fetal programming of ovarian dysfunction. Reprod Biol Endocrinol 4, 17.
35.Dumesic, DA, Abbott, DH & Padmanabhan, V (2007) Polycystic ovary syndrome and its developmental origins. Rev Endocr Metab Disord 8, 127–141.
36.Steckler, T, Wang, J, Bartol, FF et al. (2005) Fetal programming: prenatal testosterone treatment causes intrauterine growth retardation, reduces ovarian reserve and increases ovarian follicular recruitment. Endocrinology 146, 3185–3193.
37.Eisner, JR, Dumesic, DA, Kemnitz, JW et al. (2003) Increased adiposity in female rhesus monkeys exposed to androgen excess during early gestation. Obes Res 11, 279–286.
38.Legro, RS, Driscoll, D, Strauss, JF III et al. (1998) Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome. Proc Natl Acad Sci USA 95, 14956–14960.
39.Kahsar-Miller, MD, Nixon, C, Boots, LR et al. (2001) Prevalence of polycystic ovary syndrome (PCOS) in first-degree relatives of patients with PCOS. Fertil Steril 75, 53–58.
40.Yildiz, BO, Yarali, H, Oguz, H et al. (2003) Glucose intolerance, insulin resistance, and hyperandrogenemia in first degree relatives of women with polycystic ovary syndrome. J Clin Endocrinol Metab 88, 2031–2036.
41.Gharani, N, Waterworth, DM, Batty, S et al. (1997) Association of the steroid synthesis gene CYP11a with polycystic ovary syndrome and hyperandrogenism. Hum Mol Genet 6, 397–402.
42.Diamanti-Kandarakis, E, Bartzis, MI, Bergiele, AT et al. (2000) Microsatellite polymorphism (tttta)(n) at −528 base pairs of gene CYP11alpha influences hyperandrogenemia in patients with polycystic ovary syndrome. Fertil Steril 73, 735–741.
43.Carey, AH, Waterworth, D, Patel, K et al. (1994) Polycystic ovaries and premature male pattern baldness are associated with one allele of the steroid metabolism gene CYP17. Hum Mol Genet 3, 1873–1876.
44.Urbanek, M, Legro, RS, Driscoll, DA et al. (1999) Thirty-seven candidate genes for polycystic ovary syndrome: strongest evidence for linkage is with follistatin. Proc Natl Acad Sci USA 96, 8573–8578.
45.Waterworth, DM, Bennett, ST, Gharani, N et al. (1997) Linkage and association of insulin gene VNTR regulatory polymorphism with polycystic ovary syndrome. Lancet 349, 986–990.
46.Unluturk, U, Harmanci, A, Kocaefe, C et al. (2007) The genetic basis of the polycystic ovary syndrome: a literature review including discussion of PPAR-gamma. PPAR Res 2007, Article ID 49109.
47.Franks, S, Gharani, N, Waterworth, D et al. (1997) The genetic basis of polycystic ovary syndrome. Hum Reprod 12, 2641–2648.
48.Lovejoy, JC, Bray, GA, Bourgeois, MO et al. (1996) Exogenous androgens influence body composition and regional body fat distribution in obese postmenopausal women – a clinical research center study. J Clin Endocrinol Metab 81, 2198–2203.
49.Elbers, JM, Asscheman, H, Seidell, JC et al. (1997) Long-term testosterone administration increases visceral fat in female to male transsexuals. J Clin Endocrinol Metab 82, 2044–2047.
50.Escobar-Morreale, HF & San Millán, JL (2007) Abdominal adiposity and the polycystic ovary syndrome. Trends Endocrinol Metab 18, 266–272.
51.Nestler, JE, Jakubowicz, DJ, De Vargas, AF et al. (1998) Insulin stimulates testosterone biosynthesis by human thecal cells from women with polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system. J Clin Endocrinol Metab 83, 2001–2005.
52.Nestler, JE & Jakubowicz, DJ (1996) Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. N Engl J Med 335, 617–623.
53.Pierpoint, T, McKeigue, PM, Isaacs, AJ et al. (1998) Mortality of women with polycystic ovary syndrome at long-term follow-up. J Clin Epidemiol 51, 581–586.
54.Azziz, R, Marin, C, Hoq, L et al. (2005) Health care-related economic burden of the polycystic ovary syndrome during the reproductive life span. J Clin Endocrinol Metab 90, 4650–4658.
55.Salley, KE, Wickham, EP, Cheang, KI et al. (2007) Glucose intolerance in polycystic ovary syndrome – a position statement of the Androgen Excess Society. J Clin Endocrinol Metab 92, 4546–4556.
56.Wild, S, Pierpoint, T, McKeigue, P et al. (2000) Cardiovascular disease in women with polycystic ovary syndrome at long-term follow-up: a retrospective cohort study. Clin Endocrinol (Oxf) 52, 595–600.
57.Legro, RS, Azziz, R & Giudice, L (2006) A twenty-first century research agenda for polycystic ovary syndrome. Best Pract Res Clin Endocrinol Metab 20, 331–336.
58.Guzick, DS, Talbott, EO, Sutton-Tyrrell, K et al. (1996) Carotid atherosclerosis in women with polycystic ovary syndrome: initial results from a case-control study. Am J Obstet Gynecol 174, 1224–1229; discussion 1229–1232.
59.Strack, T (2008) Metformin: a review. Drugs Roday (Barc) 44, 303–314.
60.Soares, GM, Vierira, CS, De Paula Martins, W et al. (2009) Metabolic and cardiovascular impact of oral contraceptives in polycystic ovary syndrome. Int J Clin Pract 63, 160–169.
61.Knowler, WC, Barrett-Connor, E, Fowler, SE et al. (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346, 393–403.
62.Kahn, BB (1996) Lilly lecture 1995. Glucose transport: pivotal step in insulin action. Diabetes 45, 1644–1654.
63.Laviola, L, Perrini, S, Cignarelli, A et al. (2006) Insulin signalling in human adipose tissue. Arch Physiol Biochem 112, 82–88.
64.Rosen, ED & Spiegleman, BM (2006) Adipocytes as regulators of energy balance and glucose homeostasis. Nature 444, 847–853.
65.Andersen, P, Seljeflot, I, Abdelnoor, M et al. (1995) Increased insulin sensitivity and fibrinolytic capacity after dietary intervention in obese women with polycystic ovary syndrome. Metabolism 44, 611–616.
66.Moran, LJ, Noakes, M, Clifton, PM et al. (2003) Dietary composition in restoring reproductive and metabolic physiology in overweight women with polycystic ovary syndrome. J Clin Endocrinol Metab 88, 812–819.
67.Crosignani, PG, Colombo, M, Vegetti, W et al. (2003) Overweight and obese anovulatory patients with polycystic ovaries: parallel improvements in anthropometric indices, ovarian physiology and fertility rate induced by diet. Hum Reprod 18, 1928–1932.
68.Herriot, AM, Whitcroft, S & Jeanes, Y (2008) An retrospective audit of patients with polycystic ovary syndrome: the effects of a reduced glycaemic load diet. J Hum Nutr Diet 21(4):337–345.
69.Galletly, C, Moran, L, Noakes, M et al. (2007) Psychological benefits of a high-protein, low-carbohydrate diet in obese women with polycystic ovary syndrome – a pilot study. Appetite 49, 590–593.
70.Marsh, KA, Steinbeck, KS, Atkinson, FS et al. . (2010) Effect of a low glycemic index compared with a conventional healthy diet on polycystic ovary syndrome. Am J Clin Nutr 92, 83–92.
71.Douglas, CC, Gower, BA, Darnell, BE et al. (2006) Role of diet in the treatment of polycystic ovary syndrome. Fertil Steril 85, 679–688.
72.Kasim-Karakas, SE, Cunningham, WM & Tsodikov, A (2007) Relation of nutrients and hormones in polycystic ovary syndrome. Am J Clin Nutr 85, 688–694.
73.Colagiuri, S & Brand Miller, J (2002) The ‘carnivore connection’ – evolutionary aspects of insulin resistance. Eur J Clin Nutr 56, Suppl. 1, S30–S35.
74.Roche, HM (2005) Fatty acids and the metabolic syndrome. Proc Nutr Soc 64, 23–29.
75.Carmina, E, Legro, RS, Stamets, K et al. (2003) Difference in body weight between American and Italian women with polycystic ovary syndrome: influence of the diet. Hum Reprod 18, 2289–2293.
76.Mai, K, Bobbert, T, Kullmann, V et al. (2006) Free fatty acids increase androgen precursors in vivo. J Clin Endocrinol Metab 91, 1501–1507.
77.Mai, K, Bobbert, T, Reinecke, F et al. (2008) 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 93, 3900–3906.
78.Chavarro, JE, Rich-Edwards, JW, Rosner, BA et al. (2007) Dietary fatty acid intakes and the risk of ovulatory infertility. Am J Clin Nutr 85, 231–237.
79.Kasim-Karakas, SE, Almario, RU, Gregory, L et al. (2004) Metabolic and endocrine effects of a polyunsaturated fatty acid-rich diet in polycystic ovary syndrome. J Clin Endocrinol Metab 89, 615–620.
80.Wang, C, Harris, WS, Chung, M et al. (2006) n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review. Am J Clin Nutr 84, 5–17.
81.Finnegan, YE, Minihane, AM, Leigh-Firbank, EC et al. (2003) Plant- and marine-derived n-3 polyunsaturated fatty acids have differential effects on fasting and postprandial blood lipid concentrations and on the susceptibility of LDL to oxidative modification in moderately hyperlipidemic subjects. Am J Clin Nutr 77, 783–795.
82.Williams, CM (2004) Lipid metabolism in Women. Proc Nutr Soc 63, 153–160.
83.Vessby, B (2000) Dietary fat and insulin action in humans. Br J Nutr 83, Suppl. 1, S91–S96.
84.Aterburn, LM, Hall, EB & Oken, H (2006) Distribution, interconversion, and dose response of n-3 fatty acids in humans. Am J Clin Nutr 83, 1467S–1476S.
85.Deckelbaum, RJ, Worgall, TS & Seo, T (2006) n-3 fatty acids and gene expression. Am J Clin Nutr 83, 1520S–1525S.
86.Kris-Etherton, PM, Harris, WS & Appel, LJ (2002) Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 106, 2747–2757.
87.Williams, CM, Moore, F, Morgan, L et al. (1992) Effects of n-3 fatty acids on postprandial triacylglycerol and hormone concentrations in normal subjects. Br J Nutr 68, 655–666.
88.Lovegrove, JA, Lovegrove, SS, Lesauvage, SV et al. (2004) Moderate fish-oil supplementation reverses low-platelet, long-chain n-3 polyunsaturated fatty acid status and reduces plasma triacylglycerol concentrations in British Indo-Asians. Am J Clin Nutr 79, 974–982.
89.Harris, WS & Muzio, F (1993) Fish oil reduces postprandial triglyceride concentrations without accelerating lipid-emulsion removal rates. Am J Clin Nutr 58, 68–74.
90.Aitken, RJ, Baker, HW & Irvine, DS (1995) On the nature of semen quality and infertility. Hum Reprod 10, 248–249.
91.Uauy, R, Treen, M & Hoffman, DR (1989) Essential fatty acid metabolism and requirements during development. Semin Perinatol 13, 118–130.
92.Innis, SM (1986) Effect of total parenteral nutrition with linoleic acid-rich emulsions on tissue omega 6 and omega 3 fatty acids in the rat. Lipids 21, 132–138.
93.Duarte, A, Castillo, AF, Castilla, R et al. (2007) An arachidonic acid generation/export system involved in the regulation of cholesterol transport in mitochondria of steroidogenic cells. FEBS Lett 581, 4023–4028.
94.Richards, JS, Russell, DL, Ochsner, S et al. (2002) Novel signalling pathways that control ovarian follicular development, ovulation, and luteinization. Recent Prog Horm Res 57, 195–220.
95.Diamanti-Kandarakis, E, Alezandraki, K, Piperi, C et al. (2006) Inflammatory and endothelial markers in women with polycystic ovary syndrome. Eur J Clin Invest 36, 691–697.
96.Cussons, AJ, Watts, GF, Mori, TA et al. (2009) Omega-3 fatty acid supplementation decreases liver fat content in polycystic ovary syndrome: a randomized controlled trial employing proton magnetic resonance spectroscopy. J Clin Endocrinol Metab 94, 3842–3848.
97.Corton, M, Botella-Carreterro, JI, Lopez, JA et al. (2008) Proteomic analysis of human omental adipose tissue in the polycystic ovary syndrome using two-dimensional difference gel electrophoresis and mass spectrometry. Hum Reprod 23, 651–661.
98.Froment, P, Gizard, F, Defever, D et al. (2006) Peroxisome proliferator-activated receptors in reproductive tissues: from gametogenesis to parturition. J Endocrinol 189, 199–209.
99.Seto-Young, D, Paliou, M, Schlosser, J et al. (2005) Direct thiazolidinedione action in the human ovary: insulin-independent and insulin-sensitizing effects on steroidogenesis and insulin-like growth factor binding protein-1 production. J Clin Endocrinol Metab 90, 6099–6105.
100.Mansfield, R, Galea, R, Brincat, M et al. (2003) Metformin has direct effects on human ovarian steroidogenesis. Fertil Steril 79, 956–962.
101.Hibbeln, JR, Nieminen, LR & Blasbalg, TL (2006) Healthy intakes of n-3 and n-6 fatty acids: estimations considering worldwide diversity. Am J Clin Nutr 83, 1483S–1493S.