Hostname: page-component-8448b6f56d-c47g7 Total loading time: 0 Render date: 2024-04-17T18:50:11.587Z Has data issue: false hasContentIssue false

Metabolic aspects of polycystic ovary syndrome

Published online by Cambridge University Press:  03 June 2009

Robert A Wild*
Affiliation:
Section of Women's Health and Preventive Medicine, Departments of Obstetrics/Gynecology and Medicine (Cardiology), Oklahoma University Health Sciences Center, Oklahoma City, Oklahoma, USA
*
Section of Women's Health and Preventive Medicine, Departments of Obstetrics/Gynecology and Medicine (Cardiology), Oklahoma University Health Sciences Center, 920 S. Stanton L. Young Blvd., WP2410; Oklahoma City, Oklahoma 73104, USA.

Extract

Metabolic abnormalities in patients with PCO syndrome demand that we change our clinical approach to PCO syndrome. No longer should the approach be short-term and driven by symptoms, rather it must recognize that PCO syndrome is a chronic disorder. Associated metabolic abnormalities may have long-term sequelae and their recognition influences not only how we evaluate patients, but also how we implement prevention. Observational, interventional, epidemiological and now mechanistic studies need to focus on interactive issues. Outcome study results are awaited to determine the likelihood of sequelae and to optimize preventive strategies. The PCO paradigm is a complex biological experiment on nature that offers a superb opportunity to begin to understand the many ways in which hormones affect atherogenesis. It is important to understand the clinical syndromes encompassed in this paradigm. Atherogenic consequences are still responsible for the majority of deaths in the industrialized world!

Type
Research Article
Copyright
Copyright © Cambridge University Press 1997

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1Frayn, KN. Insulin resistance and lipid metabolism. Curr Opin Lipidol 1993; 4: 197204.CrossRefGoogle Scholar
2Mussoni, L, Luisa, Mannucci, Marina, Sirtori et al. Hypertriglyceridemia and regulation of fibrinolytic activity. Arteriosclerosis Thrombosis 1992; 12: 1927.CrossRefGoogle ScholarPubMed
3Jones, PH: A clinical overview of dyslipidemias: treatment strategies. Am J Med 1992; 93: 187–98.CrossRefGoogle ScholarPubMed
4Howard, BV, Howard, WJ. Dyslipidemia in diabetes mellitus. Endoer Rev 1994; 15: 263–74.Google ScholarPubMed
5Taskinen, MJ, Packard, CJ, Shepherd, J. Effect of insulin therapy on metabolic fate of apolipoprotein B-containing lipoproteins in NIDDM. Diabetes 1990; 39: 206, 207, 1017–27.CrossRefGoogle Scholar
6Mancini, M, Steiner, G, Betteridge, DJ et al. Acquired (secondary) forms of hypertriglyceridemia. Am J Cardiol 1991; 68: 17A21A.CrossRefGoogle ScholarPubMed
7Pan, XR, Cheung, MC, Waiden, CE et al. Abnormal composition of apoproteins C-I, C-II and C-III in plasma and very-low-density lipoproteins of non-insulin-dependent diabetic Chinese. Clin Chem 1986; 32: 1914–20.CrossRefGoogle Scholar
8Miller, TD, Radam, TE, O'Brien, T et al. Acute physical exercise alters apolipoprotein E and C-III concentrations of apo E-rich very low density lipoprotein fraction. Atherosclerosis 1992; 97: 3751.Google Scholar
9Laws, A, Reaven, GM. Evidence for an independent relationship between insulin resistance and fasting plasma HDL cholesterol, triglycerides and insulin concentrations. J Intern Med 1992; 231: 2530.CrossRefGoogle ScholarPubMed
10Vague, P, Raccah, D. The syndrome of insulin resistance. Horm Res 1992; 38: 2832.CrossRefGoogle ScholarPubMed
11Ostlund, RE, Staten, M, Kormt, WM et al. The ratio of waist to hip circumference, plasma insulin level and glucose intolerance as independent predictors of the HDL Cholesterol level in older men. N Engl J Med 1990; 322: 199234.CrossRefGoogle Scholar
12Barakat, HA, Carpenter, JW, McClendon, VD et al. Influence of obesity, impaired glucose tolerance, and NIDDM on LDL structure and composition. Possible link between hyperinsulinemia and atherosclerosis. Diabetes 1990; 39: 1527–33.CrossRefGoogle ScholarPubMed
13Feingold, KR, Grunfeld, C, Pang, M et al. LDL subclass phenotypes and triglyceride metabolism in non-insulin-dependent diabetes. Arterioscler Thromb 1992; 12: 1496–502.CrossRefGoogle ScholarPubMed
14Sharrett, AR, Chambles, LE, Heiss, G et al. Association of postprandial triglyceride and retinyl palmitate responses with asymptomatic carotid artery atherosclerosis in middle-aged men and women. (The Atherosclerosis Risk in Communities Study). Aerterioscler Thromb Vase Biol. 1995; 15: no. 12.Google Scholar
15Durlach, V, Attia, N, Zahouani, A et al. Postprandial cholesteryl ester transfer and high-density-lipoprotein composition in norrnotriglyceridemic non-insulin-dependent diabetic-patients. Atherosclerosis 1996; 120: 155–65.CrossRefGoogle ScholarPubMed
16Austin, MA. Plasma triglyceride and coronary heart disease. Arterioscler Thromb 1991; 11: 214.CrossRefGoogle ScholarPubMed
17Talbott, E et al. Coronary heart disease risk factors in women with polycystic ovary syndrome. Arterioscler Thromb Vase Biol 1995; 15: 821–6.CrossRefGoogle ScholarPubMed
18Conway, GS, Agrawal, DJ, Betteridge, , Jacobs, HS. Risk factors for coronary artery disease in lean and obese women with the polycystic ovary syndrome. Clin Endocrinol 1992; 37: 199225.CrossRefGoogle ScholarPubMed
19Wild, RA et al. Lipid and apolipoprotein abnormalities in hirsute women. Am J Obstet Gynecol 1992; 166: 1191–7.CrossRefGoogle ScholarPubMed
20Hodis, HN, Mack, WJ, Triglyceride-rich lipoproteins and the progression of coronary artery disease, hyperlipidaemia and cardiovascular disease. Curr Sci Lipidol 1995; 6: 209–14.CrossRefGoogle Scholar
21Wild, RA, Painter, PD, Coulson, PB, Carruth, KB, Ranney, GB. Lipoprotein lipid concentrations and cardiovascular risk in patients with polycystic ovary syndrome. J Clin Endocrinol Metab 1985; 161: 946–50.CrossRefGoogle Scholar
22Lanzone, A, Fulghesu, AM, Cucinelli, F et al. Preconceptional and gestational evaluation of insulin secretion in patients with polycystic ovary syndrome. Hum Reprod 1996; 11: 2382–6.CrossRefGoogle ScholarPubMed
23Jeppesen, J et al. Relation between insulin resistance, hyperinsulinemia, postheparin plasma lipoprotein lipase activity, and postprandial lipemia. Arterioscler Thromb Vase Biol 1995; 15: 320–4.CrossRefGoogle ScholarPubMed
24Wild, RA. Role of endogenous estrogen in the hirsutism paradigm. J Reprod Med 1994; 39: 273–6.Google ScholarPubMed
25Talbott, EO, Guzick, DS, Kuller, LH, Engberd, R. Abstract 1970, 69th session AHA University of Pittsburgh, Pittsburgh, PA, USA, University Of Rochester Med. Ct. Rochester NY USA. (New Orleans, LA Nov 10–13, 1996).Google Scholar
26Blankenborn, DH, Hodis, HN. Arterial imaging and atherosclerosis reversal. Atherosclerosis Thrombosis 1994; 14: 177–92.Google Scholar
27Tangiral, RK, Rubin, EM, Palinski, W. J Lipid Res 1995; 36: 2320–8.CrossRefGoogle Scholar
28Wolden, CE, Knopp, RH, Wahl, PW. Sex differences in the effect of diabetes mellitus on lipoprotein triglyceride and cholesterol concentrations. N Engl J Med 1984; 311: 953.CrossRefGoogle Scholar
29Patsch, Jr. Triglyceride-rich lipoproteins and atherosclerosis. Atherosclerosis 1994; 110(Suppl): S236.CrossRefGoogle ScholarPubMed
30Wild, RA, Painter, PD, Coulson, PB, Carruth, KB, Ranney, GB. Lipoprotein lipid concentrations and cardiovascular risk in patients with polycystic ovary syndrome. J Clin Endocrinol Metab 1985; 61: 946–50.CrossRefGoogle ScholarPubMed
31Dahlgren, E, Johannsson, S, Lindstedt, G et al. Women with polycystic ovary syndrome wedge resected in 1956 to 1961: a long-term follow-up focusing on natural history and circulating hormones. Fertil Steril 1992; 57: 505–13.CrossRefGoogle Scholar
32Knopp, RH et al. Sex hormones and lipid interactions: implications for cardiovascular disease in women. Endocrinologist 1994; 4: 286301.CrossRefGoogle Scholar
33Dowling, HJ et al. Insulin resistance in adipocytes of obese women: effects of body fat distribution and race. Metabolism 1995; 44: 987–95.CrossRefGoogle ScholarPubMed
34Razay, G, Heaton, KW et al. Smoking habits and lipoproteins in British women. Q J Med 1995; 88: 503–8.Google ScholarPubMed
35Sanderson, KJ, Vanrij, AM, Wade, CR, Sutherland, WH. Lipid peroxidation of circulating low density lipoproteins with age, smoking and in peripheral vascular disease. Atherosclerosis 1995; 118: 4551.CrossRefGoogle ScholarPubMed
36Smith, U. Smoking elicits the insulin resistance syndrome: new aspects of the harmful effect of smoking. J Intern Med 1995; 237: 435–7.CrossRefGoogle ScholarPubMed
37Rimm, EB et al. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med 1993; 328: 1456–9.CrossRefGoogle ScholarPubMed
38Eriksson, K-F, Lindgarde, F (1991) Prevention of type 2 (non-insulin-dependent) diabetes mellitus by diet and physical-exercise. The 6-year Malmo feasibility study. Diabetologia 34: 891–8.CrossRefGoogle ScholarPubMed
39Clifton, PM et al. Body fat distribution is a determinant of the high-density lipoprotein response to dietary fat and cholesterol in women. Arterioscler Thromb Vase Biol 1995; 15: 1070–8.CrossRefGoogle ScholarPubMed
40Wiseman, H. Role of dietary phyto-oestrogens in the protection against cancer and heart disease. Biochem Soc Trans 1996; 24: 795800.CrossRefGoogle ScholarPubMed
41Yagi, K, Komura, S. Inhibitory effect of female hormones on lipid peroxidation. Biochem Int 1986; 13: 1051–5.Google ScholarPubMed
42Sugioka, K, Shimosegawa, Y, Nakano, M. Estrogens as natural antioxidants of membrane phospholipid peroxidation. FEBS Lett 1987; 210: 37–9.CrossRefGoogle ScholarPubMed
43Yoshino, K, Komura, S, Watanabe, I, Nakagawa, Y, Yagi, K. Effect of estrogens on serum and liver lipid peroxide levels in mice. J Clin Biochem Nutr 1987; 3: 233–40.CrossRefGoogle Scholar
44Nakano, M, Sugioka, K, Naito, I, Takekoshi, S, Niki, E. Novel and potent biological antioxidants on membrane phospholipid peroxidation: 2-hydroxy estrone and 2-hydroxy estradiol. Biochem Biophys Res Commun 1987; 142: 919–24.CrossRefGoogle Scholar
45Mukai, , Daifuku, K, Yokoyama, S, Nakano, M. Stopped-flow investigation of antioxidant activity of estrogens in solution. Biochim Biophys Acta 1990; 1035: 348–52.CrossRefGoogle ScholarPubMed
46Huber, LA, Scheffler, E, Poll, T, Ziegler, R, Dresel, HA. 17(Estradiol inhibits LDL oxidation and cholesterol ester formation in cultured macrophages. Free Rad Res Commun 1990; 8: 167–73.CrossRefGoogle Scholar
47Maziere, C, Auclair, M, Ronveaux, M-F, Salmon, S, Santus, R, Maziere, J-C. Estrogens inhibit copper and cell-mediated modification of low density lipoprotein. Atherosclerosis 1991; 89: 175–82.CrossRefGoogle ScholarPubMed
48Rifici, VA, Khachadurian, AK. The inhibition of low-density lipoprotein oxidation by 17β-estradiol. Metabolism 1992; 41: 1110–14.CrossRefGoogle Scholar
49Negre-Salvayre, A, Pieraggi, M-T, Mabile, L, Salvayre, R. Protective effect of 17β-estradiol against the cytotoxicity of minimally oxidized LDL to cultured bovine aortic endothelial cells. Atherosclerosis 1993; 99: 207–17.Google ScholarPubMed
50Subbiah, MTR, Kessel, B, Agrawal, M, Rajan, R, Abplanalp, W, Rymaszewski, Z. Antioxidant potential of specific estrogens on lipid peroxidation. J Clin Endocrinol Metab 1993; 77: 1095–7.Google ScholarPubMed
51Sack, MN, Rader, DJ, Cannon, RO. Oestrogen and inhibition of oxidation of low-density lipoproteins in postmenopausal women. Lancet 1994; 343: 269–70.CrossRefGoogle ScholarPubMed
52Guetta, V, Panza, JA, Waclawiw, MA, Cannon, RO. Effect of combined 17β-estradiol and vitamin E on low-density lipoprotein oxidation in postmenopausal women. Am J Cardiol 1995; 75: 1274–6.CrossRefGoogle ScholarPubMed
53Keaney, JF, Shwaery, GT, Xu, A, Nicolosi, RJ, Loscalzo, J, Foxall, TL, Vita, JA. 17β-Eestradiol preserves endothelial vasodilator function and limits low-density lipoprotein oxidation in hypercholesterolemic swine. Circulation 1994; 89: 2251–9.CrossRefGoogle Scholar
54The Coronary Drug Project Research Group. The Coronary Drug Project: initial findings leading to modifications of its research protocol. JAMA 1970; 214: 1303–13.CrossRefGoogle Scholar
55The Writing Group for the PEPI Trial. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in post-menopausal women: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA 1995; 273: 199208.CrossRefGoogle Scholar
56Nabulsi, AA, Folsom, AR, White, A, Patsch, W, Heiss, G, Wu, KK. Various cardiovascular risk factors in postmenopausal women. N Engl J Med 1993; 328: 1069–75.CrossRefGoogle ScholarPubMed
57Gebara, OCE et al. Association between increased estrogen status and increased fibrinolytic potential in the Framingham Offspring Study. Circulation 1995; 91: 1952–8.CrossRefGoogle ScholarPubMed
58Kugiyama, K et al. Transferable lipids in oxidized low-density lipoprotein stimulate plasminogen activator inhibitor-1 and inhibit tissue-type plasminogen activator release from endothelial cells. Circ Res 1993; 73: 335–43.CrossRefGoogle ScholarPubMed
59Etingin, OR, Hajjar, DP et al. Lipoprotein (a) regulates plasminogen activator inhibitor-1 expression in endothelial cells. J Biol Chem 1991; 266: 2459–65.CrossRefGoogle ScholarPubMed
60Lerman, A, Webster, MWI, Chesebro, JH et al. Circulating and tissue endothelin immunoreactivity in hypercholesterolemic pigs. Circulation 1993; 88: 2923–8.CrossRefGoogle ScholarPubMed
61Polderman, KH, Stehouwer, CDA, van Kamp, GJ et al. Influence of sex hormones on plasma endothelin levels. Ann Intern Med 1993; 118: 429–32.CrossRefGoogle ScholarPubMed
62Hayashi, T, Fukuto, JM, Ignarro, U, Chaudhuri, G. Basal release of nitric oxide from aortic rings is greater in female rabbits than male rabbits: implications for atherosclerosis. Proc Natl Acad Sci USA 1992; 89: 11259–63.CrossRefGoogle ScholarPubMed
63Van Buren, GA, Yang, D, Clark, KE. Estrogeninduced uterine vasodilatation is antagonized by l-nitroarginine methyl ester an inhibitor of nitric oxide synthesis. Am J Obstet Gynecol 1992; 167: 828–33.CrossRefGoogle ScholarPubMed
64Weiner, CP, Lizasoain, I, Baylis, SA et al. Induction of calcium-dependent nitric oxide synthases by sex hormones. Proc Natl Acad Sci USA 1994; 91: 5212–16.CrossRefGoogle ScholarPubMed
65Schray-Utz, B, Zeiher, AM, Busse, R. Expression of constitutive NO synthase in cultured endothelial cells is enhanced by 17β-estradiol [Abstract]. Circulation 1993; 88(Suppl 1): 180.Google Scholar
66Caulin-Glaser, TL, Sessa, W, Sarrel, P, Bender, J. The effect of 17β-estradiol in human endothelial cell nitric oxide production [Abstract]. Circulation 1994; 90(Suppl 1): 130.Google Scholar
67Sayegh, HS, Ohara, Y, Navas, JP, Peterson, TE et al. Endothelial nitric oxide synthase regulation by estrogens [Abstract]. Circulation 1993; 88(Suppl 1): 180.Google Scholar
68Rosselli, M, Imthurn, B, Keller, PJ, Jackson, EK et al. Circulating nitric oxide (nitrite/nitrate) levels in postmenopausal women substituted with 17β-estradiol and norethisterone acetate. Hypertension 1995; 25: 848–53.CrossRefGoogle ScholarPubMed
69Moneada, S, Higgs, A. The l-arginine-nitric oxide pathway. N Engl J Med 1993; 329: 2002–12.Google Scholar
70Cooke, JP, Tsao, PS. Cytoprotective effects of nitric oxide. Circulation 1993; 88: 2451–4.CrossRefGoogle ScholarPubMed
71Furchgoit, RF, Zawadzki, JV. The obligatory role of the endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980; 288: 373–6.CrossRefGoogle Scholar
72Palmer, RM, Ferrige, AG, Moneada, S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987; 327: 524–6.CrossRefGoogle ScholarPubMed
73Vanhoutte, PM. The endothelium: modulator of vascular smooth muscle tone. N Engl J Med 1998; 319: 512–13.CrossRefGoogle Scholar
74Rubanyi, GM, Romero, JC, Vanhoutte, PM. Flow-induced release of endothelium-derived relaxing factor. Am J Physiol 1986; 250: H1145–9.Google ScholarPubMed
75Panza, JA, Quyyumi, AA, Brush, JE, Epstein, SE. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med 1990; 323: 22–7.CrossRefGoogle ScholarPubMed
76Creager, MA, Cooke, JP, Mendelsohn, ME et al. Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans. J Clin Invest 1990; 86: 228–34.CrossRefGoogle ScholarPubMed
77Zeiher, AM, Drexler, H, Wollschlager, H, Just, B. Modulation of coronary vasomotor tone in humans: progressive endothelial dysfunction with different early stages of coronary atherosclerosis. Circulation 1991; 83: 391401.CrossRefGoogle ScholarPubMed
78Egashira, Y, Inou, T, Hirooka, Y, Yamada, A, Maruoka, et al. Impaired coronary blood flow response to acetylcholine in patients with coronary risk factors and proximal atherosclerotic lesions. J Clin Invest 1993; 91: 2937.CrossRefGoogle ScholarPubMed
79Vita, JA, Treasure, CB, Nabel, EG et al. Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease. Circulation 1990; 81: 491–7.CrossRefGoogle ScholarPubMed
80Zeiher, AM, Schachinger, V, Minners, J. Long-term cigarette smoking impairs endothelium-dependent coronary arterial vasodilator function. Circulation 1995; 92: 1094–100.CrossRefGoogle ScholarPubMed
81Chowienczyk, PJ, Watts, OF, Cockroft, JK et al. Sex differences in endothelial function in normal and hypercholesterolaemic subjects. Lancet 1994; 334: 305–6.CrossRefGoogle Scholar
82Celermajer, DS, Sorensen, KE, Spiegelhalter, DJ, Georgakopoulos, D, Robinson, J, Deanfield, JE. Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women. J Am Coll Cardiol 1994; 24: 471–6.CrossRefGoogle ScholarPubMed
83Gisclard, V, Miller, VM, Vanhoutte, PM. Effect of 17β-estradiol on endothelium-responses in the rabbit. J Pharmacol Exp Ther 1988; 244; 1922.Google Scholar
84Williams, JK, Adams, MR, Klopfenstein, HS. Estrogen modulates responses of atherosclerotic coronary arteries. Circulation 1990; 81: 1680–7.CrossRefGoogle ScholarPubMed
85Williams, JK, Adams, MR, Herrington, DM, Clarkson, TB. Short-term administration of estrogen and vascular responses of atherosclerotic coronary arteries. J Am Coll Cardiol 1992; 20: 452–7.CrossRefGoogle ScholarPubMed
86Jiang, C, Sarrell, PM, Lindsay, DC, Poole-Wilson, PA, Collins, P. Endothelium-independent relaxation of rabbit coronary artery by 17β-estradiol in vitro. Br J Phamacol 1991; 104: 1033–7.CrossRefGoogle ScholarPubMed
87Jiang, C, Sarrel, PM, Poole-Wilson, PA, Collins, P. Acute effect of 17β-estradiol on rabbit coronary artery contractile responses to endothelin-1. Am J Physiol 1993; 263: H271–2.Google Scholar
88Chester, AH, Jiang, C, Borland, JA, Yacoub, MH et al. Oestrogen relaxes human epicardial coronary arteries through non-endothelium-dependent mechanisms. Coronary Artery Dis 1995; 6: 417–22.CrossRefGoogle ScholarPubMed
89Han, S-Z, Karaki, H, Ouchi, Y, Akishita, M, Orimo, H. 17β-Estradiol inhibits Ca2+ influx and Ca2+ release induced by thromboxane A2 in porcine coronary artery. Circulation 1995; 91: 2619–26.CrossRefGoogle ScholarPubMed
90Reis, SE, Gloth, ST, Blumenthal, RS, Resar, et al. Ethinyl estradiol acutely attenuates abnormal coronary motor responses to acetylcholine in postmenopausal women. Circulation 1994; 89: 5260.CrossRefGoogle Scholar
91Gilligan, DM, Quyyumi, AA, Cannon, RO. Effects of physiological levels of estrogen on coronary vasomotor function in postmenopausal women. Circulation 1994; 89: 2545–51.CrossRefGoogle ScholarPubMed
92Herrington, DM, Braden, GA, William, JK et al. Endothelium-dependent coronary vasomotor responsiveness in postmenopausal women with and without nitrogen therapy. Am J Cardiol 1994; 73: 951–2.CrossRefGoogle Scholar
93Collins, P, Rosano, GMC, Sarrel, PM et al. 17β-Estradiol attenuates acetylcholine-induced coronary arterial constriction in woman but not men with coronary heart disease. Circulation 1995; 92: 2430.CrossRefGoogle Scholar
94DePergola, G et al. Influence of free testosterone on antigen levels of plasminogen activator inhibitor-1 in premenopausal women with central obesity. Metabolism 1992; 41: 131–4.CrossRefGoogle Scholar
95Knopp, et al. Effects of sex steroid hormones on lipoproteins, clotting, and the arterial wall. Semin Reprod Endocrinol 1996; 14: 21.CrossRefGoogle ScholarPubMed
96Adams, MR et al. Carotid intima-media thickness is only weakly correlated with the extent and severity of coronary artery disease. Circulation 1995; 92: 2127–34.CrossRefGoogle ScholarPubMed
97Bloemenkamp, KWM, Rosendaal, FR, Heimerhorst, FM et al. Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestagen. Lancet 1995; 346: 1593–6.CrossRefGoogle ScholarPubMed
98Lewis, MA, Spitzer, WO, Heinemann, LAJ et al. Third generation oral contraceptives and risk of myocardial infarction: an international case-control study. Br Med J 1996; 312: 8890.CrossRefGoogle ScholarPubMed
99Hollenbaugh, DC et al. Hyperglycemia impairs coronary microvascular endothelium-dependent vasodilation [Abstract]. Circulation 1995; 92: 1452.Google Scholar
100Williams, SB et al. Acute hyperglycemia impairs coronary microvascular endothelium-dependent vasodilation [Abstract]. Circulation 1995; 92: 1753.Google Scholar
101Igarashi, K et al. Acute cholesterol lowering therapy with LDL-apheresis improves endothelial function of the coronary microcirculation in patients with hypercholesterolemia [Abstract]. Circulation 1995; 92: W52.Google Scholar
102Li, XN et al. Genotype-specific regulation of PAI-1 expression by hypertriglyceridemic VLDL in PAI-1 genotyped cultured human endothelial cell types. Abstracts from the 68th Scientific Sessions, 1996; Suppl 1–694, 92: 3332.Google Scholar
103Li, XN et al. Genotype-specific regulation of PAI-1 expression by hypertriglyceridemic VLDL in PAI-1 genotyped cultured human endothelial cell types [Abstract]. Circulation 1995; 92: 1624.Google Scholar
104Dunaif, et al. The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome. JCE and M 1996, 81: 3299–306.Google ScholarPubMed
105Doi, H et al. Remnants of chylomicron and VLDL impair endothelium-dependent vasorelaxation [Abstract]. Circulation 1995; 91: 139.Google Scholar
106Schneider, DJ et al. Augmented porcine coronary arterial expression of plasminogen activator inhibitor type I (PAI-1 induced by insulin and fatty acids [Abstract]. Circulation 1995; 92: 1170.Google Scholar
107Naqvi, TZ et al. Variable effects of lipids on arterial injury-induced thrombus formation [Abstract]. Circulation 1995; 92: 1694.Google Scholar
108Taddei, et al. Defective l-arginine-nitric oxide pathway in offspring of essential hypertensive patients. Circulation 1996; 94: 1298–303.CrossRefGoogle ScholarPubMed
109Gama, R, Norris, F, Wright, J et al. Ann Clin Bichem 1996, 33: 190–5.Google Scholar
110Salobir-Pajnic, B et al. Fibrinolysis after myocardial infarction and venous thromboembolism in women in the reproductive period [Abstract], Thromb Haemost 1995; 73: 1139.Google Scholar
111Wild, RA et al. Clinical signs of androgen excess as risk factors for coronary artery disease. Fertil Steril 1990; 54: 255–9.CrossRefGoogle ScholarPubMed
112Guzick, DS et al. Carotid atherosclerosis in women with polycystic ovary syndrome: initial results from a case-control study. Am J Obstet Gynecol (in press)Google Scholar
113White, HD et al. Association of polycystic ovaries with coronary artery disease [Abstract]. Circulation 1994; 90: 685.Google Scholar
114Birdsall, MA. Association between polycystic ovaries and extent of coronary artery disease in women having cardiac catheterization. Ann Intern Med 1997; 126.CrossRefGoogle Scholar
115Norman, RJ, Masters, S, Hague, W et al. Hyperinsulinemia is common in family members of women with polycystic ovary syndrome. Fertil Steril 1996; 66: 942–7.CrossRefGoogle ScholarPubMed
116Makimattilia, S et al. Chronic hyperglycemia impairs endothelial function and insulin sensitivity via different mechanisms in insulin-dependent diabetes mellitus hyperglycemia and endothelial function. Circulation 1996; 494: 1276–82.CrossRefGoogle Scholar
117Haffner, SM, Miettine, H, Gaskill, SP et al. Decreased insulin-secretion and increased insulin-resistance are independently related to the 7-year risk of NIDDM in Mexican-Americans. Diabetes 1995; 44: 1386–91.CrossRefGoogle Scholar
118Lanzone, A, Fulghesu, AM, Andreani, CL et al. Insulin secretion in polycystic ovarian disease: effect of ovarian suppression by GnRH-agonist. Hum Reprod 1990; 5: 143–9.CrossRefGoogle ScholarPubMed
119Reaven, GM. Role of insulin resistance in human disease. Diabetes 37: 14951607.Google Scholar
120Nordby, G, Moan, A, Kjeldsen, SE et al. Relationship between hemorheological factors and insulin sensitivity in normotensive and hypertensive women [Abstract]. Kidney Int 1996; 49: 925.Google Scholar
121Wild, RA, Hirsutism: metabolic effects of two commonly used oral contraceptives and spironolactone. Contraception 1991; 44: 113.CrossRefGoogle ScholarPubMed
122Wild, RA, Demers, LM, Applebaum-Bowden, D et al. Hirsutism: metabolic effects of two commonly used oral contraceptives and spironolactone. Contraception 1991; 44: 113–24.CrossRefGoogle ScholarPubMed
123Klauber, N, Browne, F, Anand-apte, B, D'Amato, RJ. New activity of spironolactone, inhibition of angiogenesis in vitro and in vivo. Circulation 1996; 94: 2566–71.CrossRefGoogle ScholarPubMed
124Castello, et al. Outcome of long-term treatment with the 5α-reductase inhibitor finasteride in idiopathic hirsutism: clinical and hormonal effects during a 1-year course of therapy and 1-year follow-up, Fertil Steril 1996; 66: 734–40.CrossRefGoogle Scholar