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Testosterone pp 229-257 | Cite as

Androgens, cardiovascular risk factors and atherosclerosis

  • Arnold von Eckardstein

Abstract

Atherosclerotic coronary, cerebral, and peripheral vessel diseases are the most frequent cause of death and disability in the industrialized countries for both men and women. Before menopause both morbidity and mortality is much lower in women than in men because of atherosclerotic vessel diseases. After menopause the incidence of atherosclerotic vessel diseases increases steeply ( and Utian 1994). In Germany, for example, before age of 65 four times as many as women die because of myocardial infarction (MI). After age 75, coronary heart disease (CHD) mortality is much higher in women than in men so that finally the overall cardiovascular mortality does not differ among sexes (Statistisches Bundesamt 1997). The approximately 10-year gap in the clinical manifestation of atherosclerotic vessel diseases between men and women is usually explained by the anti-atherogenic effects of estrogens. The anti- atherogenicity of estrogens is also indicated by the high incidence of cardiovascular disease in ovariectomized women who do not substitute estrogens, and by the lower cardiovascular event rates of postmenopausal women who take estrogens (Barrett-Connor and Bush 1991; Gorodeski and Utian 1994). In addition to these clinical studies, many animal studies also provided evidence for the anti-atherogenicity of estrogens (Bourassa et al. 1996; Bruck et al. 1997). Moreover, compared to men of the same age, premenopausal women have a more favourable cardiovascular risk factor profile with higher levels of high density lipoprotein cholesterol (HDL-C) and lower levels of low density lipoprotein cholesterol (LDL-C), lipoprotein(a) (Lp(a)), homocysteine, and fibrinogen.

Keywords

Cardiovascular Risk Factor Cholesteryl Ester Polycystic Ovary Syndrome Cholesteryl Ester Transfer Protein Plasminogen Activator Inhibitor Type 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Adams MR, Williams JK, Kaplan JR (1995) Effects of andogens on coronary artery atherosclerosis and atherosclerosis-related impairment of vascular responsiveness. Arterioscler Thromb Vase Biol 15: 562–570Google Scholar
  2. Aikawa K, Furuchi T, Fujimoto Y, Arai H, Inoue K (1994) Structure-specific inhibiton of lysosomal cholesterol transport in macrophages by various steroids. Biochim Biophys Acta 1213: 127–134PubMedGoogle Scholar
  3. Akishita M, Ouchi Y, Miyoshi H, Kozaki K, Inoue S, Ishikawa M, Eto M, Toba K, Orimo H (1997) Estrogen inhibits cuff-induced intimal thickening of rat femoral artery: effects on migration and proliferation of vascular smooth muscle cells. Atherosclerosis 130: 1–10PubMedGoogle Scholar
  4. Albers JJ, Tu A-Y, Wolfbauer G, Cheung MC, and Marcovina SM (1996) Molecular biology of phospholipid transfer protein. Curr Opin Lipidol 7: 88–93PubMedGoogle Scholar
  5. Alexandersen P, Haarbo J, Christiansen C (1996) The relationship of natural androgens to coronary heart disease in males: a review. Atherosclerosis 125: 1–13PubMedGoogle Scholar
  6. Andersen P, Seljeflot I, Abdelnoor A, Arnesen M, Dale PO, Lovik A, Birkeland K (1995 a) Increased insulin sensitivity and fibrinolytic capacity in obese women with polycystic ovary syndrome. Metabolism 44: 611–616Google Scholar
  7. Andersen RA, Ludlam CA, Wu CW (1995 b) Haemostatic effects of supraphysiological levels of testosterone in normal men. Thromb Haemost 74: 693–697Google Scholar
  8. Angelin B (1997) Therapy for lowering lipoprotein(a) levels. Curr Opin Lipidol 8: 337–341PubMedGoogle Scholar
  9. Arad Y, Badimon JJ, Badimon L, Hembree WC, Ginsberg HN (1989) Dehydorepiandroster- one feeding prevents aortic fatty streak formation and cholesterol accumulation in cholesterol-fed rabbits. Arteriosclerosis 9: 159–165PubMedGoogle Scholar
  10. Arrer E, Jungwirth A, Mack D, Frick J, Patsch W (1996) Treatment of prostate cancer with gonadotropin releasing hormone analogue: effect on lipoprotein (a). J Clin Endocrinol Metab 81: 2508–2511PubMedGoogle Scholar
  11. Asscheman H, Gooren LJG, Megens JAJ, Nauta J, Klosterboer HJ, Eikelboom F (1994) Serum testosterone level is the major determinant of the male-female differences in serum levels of high-densitiy lipoprotein (HDL) cholesterol and HDL 2 cholesterol. Metabolism 43: 935–939PubMedGoogle Scholar
  12. Assmann G, Schulte H, von Eckardstein A (1996) Hypertriglyceridemia and elevated levels of lipoprotein(a) are risk factors for major coronary events in middle-aged men. Am J Cardiol 77: 1179–1184PubMedGoogle Scholar
  13. Bagatell CJ, Bremner WJ (1995) Androgen and progestagen effects on plasma lipids. Prog Cardiovasc Dis 38: 255–271PubMedGoogle Scholar
  14. Bagatell CJ, Knopp RH, Vale WW, Rivier JE, Bremner WJ (1992) Physiologic testosterone levels in normal men suppress high-density lipoprotein cholesterol levels. Ann Intern Med 116: 967–973PubMedGoogle Scholar
  15. Bagatell CJ, Heiman JR, Matsumoto AM, Rivier JE, Bremner WJ (1994) Metabolic and behavioural effects of high dose exogenous testosterone in healthy men. J Clin Endocrin Metab 79: 561–567Google Scholar
  16. Barnes R, Rosenfeld R (1989) The polycystic ovary syndrome: Pathogenesis and treatment. Ann Intern Med 110: 386–397Google Scholar
  17. Barret-Connor EL (1995) Testosterone and risk factors for cardiovascular disease in men. Diabetes Metab 21: 156–161Google Scholar
  18. Barrett-Connor EL, Bush TL (1991) Estrogen and coronary heart disease in women. JAMA 265: 1861–1867PubMedGoogle Scholar
  19. Barrett-Connor EL, Goodman-Gruen D (1995) Prospective study of endogenous sex hormones and fatal cardiovascular disease in postmenopausal women. Br Med J 311:1193– 1196Google Scholar
  20. Barrett-Connor EL, Khaw KT, Yen SSC (1986) A prospective study of dehydroepiandroster- onesulfate, mortality, and cardiovascular disease. N Engl J Med 315: 1519–1524PubMedGoogle Scholar
  21. Barrett-Connor EL, Khaw KT (1987) Absence of an inverse relation of dehydroepiandrostero- nesulfate with cardiovascular mortality in postmenopausal women. N Engl J Med 317: 711PubMedGoogle Scholar
  22. Barrett-Connor EL, Khaw KT (1988) Endogenous sex hormones and cardiovascular disease in men: a prospective population based study. Circulation 78: 539–545PubMedGoogle Scholar
  23. Behre HM, Böckers A, Schlingheider A, Nieschlag E (1994) Sustained suppression of serum LH, FSH, and testosterone and increase of high-density lipoprotein cholesterol by daily injections of the GnRH antagonist cetrorelix over 8 days in normal men. Clin Endocrinol (Oxf ) 40: 241–248Google Scholar
  24. Behre HM, Simoni M, Nieschlag E (1997) Strong association between serum levels of leptin and testosterone in men. Clin Endocrinol 47: 237–240Google Scholar
  25. Bennet A, Sie P, Caron P, Boneu B, Bazex J, Pontonnier F, Barret A, Louvet JP (1987) Plasma fibrinolytic activity in a group of hypogonadic men. Scand J Clin Lb Invest 47: 23–27Google Scholar
  26. Berglund L, Carlström K, Stege R, Gottlieb C, Eriksson M, Angelin B, Henriksson P (1996) Hormonal regulation of serum lipoprotein(a) levels: effects of parenteral administration of estrogen or testosterone in males. J Clin Endocrinol Metab 81: 2633–2637PubMedGoogle Scholar
  27. Birdsall M, Farquhar C, White H (1997) Association between polycystic ovaries and extent of coronary artery disease in women having cardiac catheterization. Ann Intern Med 126: 32–35PubMedGoogle Scholar
  28. Bjarnasson NH, Bjarnason K, Haarbo J, Coelingh Bennink HJT, Christiansen C (1997) Tibo-lone: Influence on markers of cardiovascular disease. J Clin Endocrinol Metab 82:1752– 1756Google Scholar
  29. Björntorp P ( 1993 ) Hyperandrogenicity in women - a prediabetic condition? J Intern Med 234: 579–83PubMedGoogle Scholar
  30. Björntorp P (1994) Fatty acids, hyperinsulinemia, and insulin resistance: which comes first? Curr Opin Lipidol 5: 166–174PubMedGoogle Scholar
  31. Björntorp P (1996) The regulation of adipose tissue distribution in humans. Int J Obesity 20: 291–302Google Scholar
  32. Boerwinkle E, Leffert CC, Lin J, Lackner C, Chiesa G, Hobbs HH (1992) Apolipoprotein(a) gene accounts for greater than 90% of the variation in plasma lipoprotein(a) concentrations. J Clin Invest 90: 52–60PubMedGoogle Scholar
  33. Bourassa PAK, Milos MM, Gaynor BJ, Breslow JL, Aielllo, RJ (1996) Estrogen reduces atherosclerotic lesion development in apolipoprotein E deficient mice. Proc Natl Acad Sci USA 93: 10022–10027Google Scholar
  34. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG (1995) A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA. 274: 1049–57Google Scholar
  35. Brinton EA, Eisenberg S, Breslow JL (1994) Human HDL-cholesterol levels are determined by apoA-I fractional catabolic rate, which correlates inversely with estimates of HDL size. Arterioscler Thromb 14: 707–720PubMedGoogle Scholar
  36. Bruck B, Brehme B, Gugel N, Hanke S, Finking G, Lutz C, Benda N, Schmahl FW, Haasis R, Hanke H (1997) Gender-specific differences in the effects of testosterone and estrogen on the development of atherosclerosis in rabbits. Arterioscler Thromb Vase Biol 17:2192– 2199Google Scholar
  37. Busse R, Fleming I (1996) Endothelial dysfunction in atherosclerosis. J Vase Res 33: 181–94Google Scholar
  38. Caron P, Bennet A, Camare R, Louvet JP, Boneu S, Sie P (1989) Plasminogen activator inhibitor in plasma is related to testosterone in men. Metabolism 38: 1010–1015PubMedGoogle Scholar
  39. Cauley JA, Gutai JP, Kuller LD, Dai WS (1987) Usefulness of sex steroid hormone levels in predicting coronary artery disease in men. Am J Cardiol 60:771 –777Google Scholar
  40. Chang RJ, Nakamura RM, Judd HL, Kaplan SA (1983) Insulin resistance in nonobese patients with polycystic ovarian disease. J Clin Endocrinol Metabol 57: 356–359Google Scholar
  41. Chou TM, Sudhir K, Hutchison SJ, Ko E, Amidon TM, Collins P, Chatterjee K (1996). Testosterone induces dilatation of canine coronary conductance and resistance arteries in vivo. Circulation 94: 2614–2619PubMedGoogle Scholar
  42. Contoreggi CS, Blackman MR, Andres R, Müller DC, Lakatta EG, Fleg JL, Harman SM (1990) Plasma levels of estradiol, testosterone, and DHEAS do not predict risk of coronary artery disease in men. J Androl 11: 460–470PubMedGoogle Scholar
  43. Conway GS, Agrawal R, Betteridge DJ, Jacobs HS (1992) Risk factors for coronary artery disease in lean and obese women with the polycystic ovary syndrome. Clin Endocrinol 37:119– 25Google Scholar
  44. Conway GS, Clark PM, Wong D (1993) Hyperinsulinaemia in the polycystic ovary syndrome confirmed with a specific immunoradiometric assay for insulin. Clin Endocrinol 38:219– 22Google Scholar
  45. Cortees-Prieto J (1987) Coagulation and fibrinolysis in postmenopausal women treated with Org OD 14. Maturitas 1: 67–83Google Scholar
  46. Costarella CE, Stallone JN, Rutecki GW, Whittier FC (1996) Testosterone causes direct relaxation of rat thoracic aorta. J Pharmacol Experiment Therap 277: 34–39Google Scholar
  47. Dahlgren E, Johannson S, Lindstedt G, Knutsson F, Oden A, Janson P O, Mattson L A, Crona N and Lundberg PA (1992 a) Woman with polycystic ovary syndrome wedge resected in 1956 to 1965: A long-term follow-up focussing on natural history and circulating hormones Fertil Steril 57: 505–513Google Scholar
  48. Dahlgren E, Janson PO, Johansson S, Lapidus L, Oden A (1992 b) Polycystic ovary syndrome and risk for myocardial infarction: evaluated from a risk factor model based on a prospective population study of women. Acta Obstet Gynecol Scand 71: 599–604Google Scholar
  49. Dahlgren E, Lapidus A, Janson P, Lindstedt G, Johannson S, Tengborn L (1994) Hemostatic and metabolic variables in women with polycystic ovary syndrome. Fertil Steril 61:455– 460Google Scholar
  50. Despres JP, Marette A (1994) Relation of components of insulin resistance syndrome to coronary disease risk. Curr Opin Lipidol 5: 274–289PubMedGoogle Scholar
  51. Despres JP, Lamarche B, Mauriege P, Cantin B, Dagenais GR, Moorjani S, Lupien PJ (1996) Hyperinsulinemia as independent risk factor for ischemic heart disease. N Eng J Med 334: 952–957Google Scholar
  52. Dunaif A, Mandeli J, Fluhr H, Dobrjansky A (1988) The impact of obesity on chronic hyper-insulinemia on gonadotropin release and gonadal steroid secretion in the polycystic ovary syndrome. J Clin Endocrinol Metabol 66: 131–139Google Scholar
  53. Ehrmann DA, Schneider DJ, Sobel BE, Cavaghan MK, Imperial J, Rosenfield RL, Polonsky KS (1997) Troglitazone improves defects in insulin action, insulin secretion, ovarian steroidogenesis, and fibrinolysis in women with polycystic ovary syndrome. J Clin Endocrinol Metab 82: 2108–2116PubMedGoogle Scholar
  54. Eich DM, Nestler JE, Johnson DE, Dworkin GH, Ko D, Wechsler AS, Hess ML (1993) Inhibition of accelerated coronary atherosclerosis with dehydroepinadrosterone in the heterotopic rabbit model of cardiac transplantation. Circulation 87: 261–265PubMedGoogle Scholar
  55. Eri LM, Urdal P (1995 a) Effects of the nonsteroidal androgen casodex on lipoproteins, fibrinogen and plasminogen activator inhibitor in patients with benign prostatic hyperplasia. Eur J Urol 27: 274–279Google Scholar
  56. Eri LM, Urdal P, Bechensteen AG (1995 b) Effects of the luteinizing hormone-releasing hormone agonist leuprolide on lipoproteins, fibrinogen and plasminogen activator inhibitor in patients with benign prostatic hyperplasia. J Urol 154: 100–104Google Scholar
  57. Ernst E, Resch KL (1993) Fibrinogen as a cardiovascular risk factor: A meta-analysis and review of the literature. Ann Intern Med 118: 956–965Google Scholar
  58. Evans RM (1988) The steroid and thyroid hormone receptor superfamily. Science 240:889– 895Google Scholar
  59. Farhat MY, Wolfe R, Vargas R, Foegh ML, Ramwell (1995) Effect of testosterone treatment on vasoconstrictor response of left anterior descending coronary artery in male and female pigs. J Cardiovasc Pharmacol 25: 495–500Google Scholar
  60. Fogelberg M, Bjorkhem I, Diczfalusy U, Henriksson P (1990) Stanozolol and experimental atherosclerosis: atherosclerosis development and blood lipids during anabolic steroid therapy of New Zealand white rabbits. Scand J Clin Lab Invest 50: 693–700PubMedGoogle Scholar
  61. Franks S (1989) Polycystic ovary syndrome: a changing perspective. Clin Endocrinol 31:87– 120Google Scholar
  62. Frayn KN (1993) Insulin resistance and lipid metabolism. Curr Opin Lipidol 4: 197–204Google Scholar
  63. Frazer KA, Narla G, Zhang JL, Rubin EM (1995). The apolipoprotein(a) gene is regulated by sex hormones and acute phase inducers in YAC transgenic mice. Nature Genetics 9:424– 431Google Scholar
  64. Freedman DS, O’Brien TR, Flanders WD (1991) Relation of serum testosterone levels to high density lipoprotein cholesterol and other characteristics in men. Arterioscler Thromb 11: 307–315PubMedGoogle Scholar
  65. Friedel DKE, Hannan CJ, Jones RE, Kettler TM, Plymate SR (1990) High density lipoprotein cholesterol is not decreased if an aromatizable androgen is administered. Metabolism 39: 69–77Google Scholar
  66. Fuster V (1994) Mechanisms leading to myocardial infarction: insights from studies in vas-cular biology. Circulation 90: 2126–2146PubMedGoogle Scholar
  67. Glazer G (1991) Atherogenic effects of anabolic steroids on serum lipid levels. Steroids 151: 1925–1933Google Scholar
  68. Glueck CJ, Gartside P, Fallat RW, Mendoza S (1976) Effect of sex hormones on protamine inactivated and resistant postheparin plasma lipase. Metabolism 25: 625–630PubMedGoogle Scholar
  69. Glueck CJ, Glueck HI, Stroop D, Speirs J, Hamer T, Tracy T (1993) Endogenous testosterone, fibrinolysis, and coronary heart disease risk in hyperlipidemic men. J Lab Clin Med 122: 412–420PubMedGoogle Scholar
  70. Goldberg IJ (1996) Lipoprotein lipase and lipolysis: Central roles in lipoprotein metabolism and atherogenesi. J Lipid Res 37: 693–707PubMedGoogle Scholar
  71. Goldberg RB, Rabin D, Alexander AN, Coelle GC, Getz GS (1985) Suppression of plasma testosterone leads to increase in serum total and high density lipoprotein cholesterol and apoproteins A-I and B. J Clin Endocrinol Metab 60: 203–207PubMedGoogle Scholar
  72. Gordon GB, Bush DE, Weisman HF (1988) Reduction of atherosclerosis by administration of dehydroepiandrosterone: A study in the hypercholesterolemic New Zealand white rabbit with aortic intimal injury. J Clin Invest 82: 58–64Google Scholar
  73. Gorodeski Gl, Utian WH (1994) Epidemiology and risk factors of cardiovascular disease in postmenopausal women. In: Lobo RA (ed) Treatment of the postmenopausal woman: basic and clinical aspects. Raven Press New York NY pp 199–221Google Scholar
  74. Graf MJ, Richards CJ, Brown V, Meissner L, Dunaif A (1990) The independent effects of hyperandrogenaemia, hyperinsulinaemia, and obesity on lipid and lipoprotein profiles in women. Clin Endocrinol 33: 119–131Google Scholar
  75. Griendling KK, Alexander RW (1996) Endothelial control of the cardiovascular system: recent advances. FASEB J 10: 283–292PubMedGoogle Scholar
  76. Guzick DS, Talbott EO, Sutton-Tyrell K, Herzog HC, Kuller LH, Wolfson SK (1996), Carotid atherosclerosis in women with polycystic ovary syndrome: Initial results from a case control study. Am J Obstet Gynecol 174: 1224–1232Google Scholar
  77. Haffner SM (1996) Sex hormone-binding protein, hyperinsulinemia, insulin resistance and noninsulin-dependent diabetes. Horm Res 45: 233–237PubMedGoogle Scholar
  78. Haffner SM, Valdez RA (1995) Endogenous sex hormones: impact on lipds, lipoproteins, and insulin. Am J Med 98 (Suppl): S40–S47Google Scholar
  79. Hämäläinen E, Adlercreutz H, Ehnholm C (1986) Relationship of serum lipoproteins and apoproteins to the binding capacity of sex hormone binding globulin in healthy Finnish men. Metabolism 35: 535–541PubMedGoogle Scholar
  80. Hamm L (1942) Testosterone propionate in the treatment of angina pectoris. J Clin Endocrinol 2: 325–328Google Scholar
  81. Hamsten A, Karpe F, Bavenholm P, Silveira A (1994) Interactions amongst insulin, lipoproteins, and hemostatic function relevant to coronary heart disease. J Int Med 236 (Suppl 736): 75–88Google Scholar
  82. Hayes R, Chalmers SA, Nikolic-Paterson DJ, Atkins RC, Hedger MP (1996) Secretion of bioactive interleukin 1 by rat testicular macrophages in vitro. J Androl 17: 41–49PubMedGoogle Scholar
  83. Henriksson P, Angelin B, Berglund L (1992) Hormonal regulation of serum Lp(a) levels. J Clin Invest 89: 1166–1171PubMedGoogle Scholar
  84. Herman SM, Robinson JTC, McCredie RJ, Adams MR, Boyer MJ, Celermajer DS (1997) Androgen deprivation is associated with enhanced endothelium-dependent dilatation in adult men. Arterioscler Thromb Vase Biol 17: 2004–2009Google Scholar
  85. Higashiura K, Mathur RS, Halushka PV (1997) Gender-related differences in androgen regulation of thromboxan A2 receptors in rat aortic smooth muscle cells. J Cardiovasc Pharmacol 29: 311–315PubMedGoogle Scholar
  86. Hishikawa K, Nakaki T, Marumo T, Suzuki H, Kato R, Saruta T (1995) Up regulation of nitric oxide synthase by estradiol in human aortic endothelial cells. FEBS Lett 360: 291–295PubMedGoogle Scholar
  87. Holte J, Bergh T, Berne C, Lithell H (1994) Serum lipoprotein lipid profile in women with the polycystic ovary syndrome: relation to anthropometric, endocrine and metabolic variables. Clin Endocrinol 41: 463–471Google Scholar
  88. Hromadova M, Hacik T, Malatinsky E, Sklovsky A, Cervenakov I (1989) Some measures of lipid metabolism in young sterile men before and after testosterone treatment. Endoc Exp 23: 205–211Google Scholar
  89. Hutchison SJ, Sudhir K, Chou TM, Chatterjee K (1997 a) Sex hormones and vascular reactivity. Herz 22: 141–150Google Scholar
  90. Hutchison SJ, Sudhir K, Chou TM, Sievers RE, Zu BQ, Sun YP, Deedwania PC, Glantz SA, Parmely WW, Chatterjee K (1997b) Testosterone worsens endothelial dysfunction associated with hypercholesterolemia and environmental tobacco smoke exposure in male rabbit aorta. J Am Coll Cardiol 29: 800–807PubMedGoogle Scholar
  91. International Task Force for the Prevention of Coronary Heart Disease (1992) Prevention of coronary heart disease: scientific background and new clinical guidelines. Nutr Metab Cardiovasc Dis 2: 113–156Google Scholar
  92. Jaffe MD (1977) Effect of testosterone on on postexercise ST segment depression. Br Heart J 39: 1217–1222PubMedGoogle Scholar
  93. Jang Y, Lincoff AM, Plow EF, Topol EJ (1994) Cell adhesion molecules in coronary artery disease. J Am Coll Cardiol 24: 1591–1601PubMedGoogle Scholar
  94. Jonas A (1991) Lecithin:cholesterol acyltransferase in the metabolism of high density lipoproteins. Biochim Biophys Acta 1084: 205–225PubMedGoogle Scholar
  95. Juhan-Vague I, Alessi MC, Nalbone G (1993) Fibrinolysis and atherothrombosis. Curr Opin Lipidol 4: 477–483Google Scholar
  96. Kiel DP, Baron CA, Plymate SR (1989) Sex hormones and lipoproteins in men. Am J Med 87: 35–39PubMedGoogle Scholar
  97. Kirkland RT, Keenan BS, Probstfield JL, Patsch W, Tsai-Lien L, Clayton GW, Insull W Jr (1987) Decrease in plasma high density lipoprotein cholesterol levels at puberty in boys with delayed adolesence: Correlation with plasma testosterone levels. JAMA 257: 502–507Google Scholar
  98. Kolodgie FD, Jacob A, Wilson PS, Carlson GC, Farb A, Verma A, Virmani R (1996) Estradiol attenuates directed migration of vascular smooth muscle cells in vitro. Am J Pathol 148: 969–976PubMedGoogle Scholar
  99. LaCroix AZ, Yano K, Reed DM (1992) Dehydroepiandrosteronsulfate, incidence of myocardial infarction, and extent of atherosclerosis in men. Circulation 86: 1529–1534PubMedGoogle Scholar
  100. Larsen BA, Nordestgaard B, Stender S, Kjeldsen K (1993) Effect of testosterone on athero- genesis in cholesterol-fed rabbits with similar plasma cholesterol levels. Atherosclerosis 99: 79–86PubMedGoogle Scholar
  101. Laughlin GA, Morales AJ, Yen SSC (1997) Serum leptin levels in women with polycystic ovary syndrome: The role of insulin resistence hyperinsulinemia. J Clin Endocrinol Metab 82: 1692–1696Google Scholar
  102. Leenen R, van der Kooy K, Scidell JC, Deurenberg P, Koppeschaar HP (1994) Visceral fat accumulation in relation to sex hormones in obese men and women undergoing weight loss therapy. J Clin Endocrinol Metab 78: 1515–1520PubMedGoogle Scholar
  103. Lesser MA (1943) The treatment of angina pectoris with testosterone propionate: Further observation. N Eng J Med 228: 185–188Google Scholar
  104. Levine S, Likoff W (1943) The therapeutic value of testosterone propionate in angina pectoris. N Eng J Med 228: 770–773Google Scholar
  105. Libby P (1995) Molecular bases of the acute coronary syndromes. Circulation 91: 2844–2850PubMedGoogle Scholar
  106. Lindstedt G, Lundberg P, Lapidus L, Lundgren H, Bengtsson C, Björntorp P (1991) Low sex hormone binding globulin concentration as an independent risk factor for development of NIDDM: 12 yr follow up of population study of women in Gothenburg. Diabetes 40: 123–128PubMedGoogle Scholar
  107. Lobo RA (1991) Clinical Review 27: effects of hormonal replacement on lipids and lipoproteins in postmenopausal women. J Clin Endocrinol Metab 73: 925–930PubMedGoogle Scholar
  108. Lönnquist F, Schalling M (1997) Role of leptin and its receptor in human obesity. Curr Opin Endocrinol Diabetes 4: 164–171Google Scholar
  109. Lüscher TF (1993) The endothelium as a target and mediator of cardiovascular disease. Eur J Clin Invest 23: 670–685PubMedGoogle Scholar
  110. Mäher VMG, Brown BG (1995) Lipoprotein(a) and coronary heart disease. Curr Opin Lipi- dol 6: 229–235Google Scholar
  111. Mammen EF (1993) Androgens and antiandrogens. Gynecol Endocrinol 7 (Suppl) 79–86 Mantzoros CS, Dunaif A, Flier JS (1997) Leptin concentrations in the polycystic ovary syndrome. J Clin Endocrinol Metab 82: 1687–1691Google Scholar
  112. Marcovina SM, Lippi G, Bagatell CJ, Bremner WJ (1996) Testosterone-induced suppression of lipoprotein (a) in normal men: relation to basal lipoprotein(a) level. Atherosclerosis 122: 89–95PubMedGoogle Scholar
  113. Marin P, Holmäng S, Jönsson L, Sjöstrom L, Kvist H, Holm G, Lindstedt G, Björntorp P (1992) The effects of testosterone treatment on body composition and metabolism in middle aged men. Int J Obesity 16: 991–997Google Scholar
  114. Marin P, Holmäng S, Gustafsson C, Jönsson L, Kvist H, Elander A, Eldh J, Sjöstrom L, Holm G, Björntorp P (1993) Androgen treatment of abdominally obese men. Obesity Res 1: 245–251Google Scholar
  115. Marin P, Oden B, Björntorp P (1995) Assimilation and mobilization of triglycerides in sub-cutaneous abdominal and femoral adipose tissue in vivo in men: effects of androgens. J Clin Endocrinol Metab 80: 239–243PubMedGoogle Scholar
  116. Masuda A, Mathur A, Halushka PV (1995) Testosterone increases thromboxane A2 receptors in cultured rat smooth muscle cells. Circ Res 69: 638–643Google Scholar
  117. Mattson LA, Cullberg G, Hamberger L, Samsioe G, Silverstolpe G (1984) Lipid metabolism in women with polycystic ovary syndrome: possible implications for an increased risk for coronary heart disease. Fertil Steril 42: 579–84Google Scholar
  118. McCrohon JA, Walters WAW, Robinson JC, McCredie RJ, Turner L, Adams MR, Handelsman DJ, Celermajer DS (1997) Arterial reactivity is enhanced in genetic males taking high dose estrogens. J Am Coll Cardiol 29: 1432–1436PubMedGoogle Scholar
  119. McEwen (1991) Non-genomic and genomic effects of steroids on neural activity. Trends Pharmacol Sci 12: 141–147PubMedGoogle Scholar
  120. McNutt RA, Ferenchick GS, Kirlin PA, Hamlin NJ (1988) Acute myocardial infarction in a 22 year old world class weightlifter abusing anabolic steroids. Am J Cardiol 62: 164–167PubMedGoogle Scholar
  121. Mendoza SG, Osuna A, Zerpa A, Gartside PS, Glueck CJ (1981) Hypertriglyceridemia and hypoalphalipoproteinemia in azoospermic and Oligospermie young men: relationships of endogenous testosterone to triglyceride and high density lipoprotein metabolism. Metabolism 30: 481–486PubMedGoogle Scholar
  122. Meriggiola MC, Bremner WJ, Paulsen CA (1995) Testosterone enanthate at a dose of 200 mg/week decreases HDL-cholesterol levels in healthy men. Int J Androl 18: 237–242PubMedGoogle Scholar
  123. New G, Timmins KL, Duffy SJ, Tran BT, O’Brien RC, Harper RW, IT Meredith IA (1997) Long-term estrogen therapy improves vascular function in male to female transsexuals. J Am Coll Cardiol 29: 1437–1444PubMedGoogle Scholar
  124. Newcomer LM, Manson JE, Barbierir JL, Hennekens CH, Stampfer MJ (1994) Dehydroepin- androsterone sulfate and the risk of myocardial infarction in US male physicians: a prospective study. Am J Epidemiol 140: 870–877PubMedGoogle Scholar
  125. NIH Consensus Development Panel on Triglyceride, High Density Lipoprotein, and Coronary Heart Disease (1993). JAMA 269: 505–510Google Scholar
  126. Olivecrona G, Olivecrona T (1995) Triglyceride lipases and atherosclerosis. Curr Opin Lipidol 6: 291–305PubMedGoogle Scholar
  127. Owens GK (1995) Regulation and differentiation of vascular smooth muscle cells. Physiol Rev 75: 487–517PubMedGoogle Scholar
  128. Ozata M, Yildrimkaya M, Bulur M, Yilmaz K, Bolu E, Corakci A, Gundogan MA (1996) Effects of gonadotropin and testosterone treatment on lipoprotein(a), high density lipo-protein particles, and other lipoprotein levels in male hypogonadism. J Clin Endocrinol Metab 81: 3372–3378PubMedGoogle Scholar
  129. Pasquali R, Casimiri F, De Iasio R, Mesini P, Boschi S, Chierici R, Flamia R, Biscotti M, Vicennati V (1995) Insulin regulates testosterone and sex-hormone binding globulin concentrations in adult normal weight and obese men. J Clin Endocrinol Metab 80: 654–658PubMedGoogle Scholar
  130. Peinado-Onsurbe J, Staels B, Vanderschueren D, Bouillon R, Auwerx J (1993) Effects of sex steroids on hepatic and lipoprotein lipase activity and mRNA in the rat. Horm Res 40: 184–188PubMedGoogle Scholar
  131. Philips GB, Yano K, Stemmermann GN (1988) Serum sex hormones and myocardial infarc-tion in the Honolulu Heart Program: pitfalls in prospective studies on sex hormones. J Clin Epidemiol 41: 1151–1156Google Scholar
  132. Phillips GB, Pinkernell BH, Jing TY (1994) The association of hypotestosteronemia with coronary artery disease in men. Arterioscler Thromb 14: 701–706PubMedGoogle Scholar
  133. Phillips GB, Pinkernell BH, Jing TY (1997) Relationship between serum sex hormones and coronary artery disease in postmenopausal women. Arterioscler Thromb Vase Biol 17: 695–701Google Scholar
  134. Pilo R, Aharony D, Raz A (1981) Testosterone potentiation of ionophere and ADP induced platelet aggregation: relationship to arachidonic acid metabolism. Thromb Haemost 46: 538–542PubMedGoogle Scholar
  135. Reaven GM (1988) Role of insulin resistance in human disease. Diabetes 37: 1495–1607Google Scholar
  136. Rebuffe-Scrive M, Marin P, Bjorntorp P (1991) Effect of testosterone on abdominal adipose tissue in men. Int J Obes 15: 791–5PubMedGoogle Scholar
  137. Rigotti A, Trigatti B, Babitt J, Penman M, Xu S, Krieger M (1997) Scavenger receptor B1 - a cell surface receptor for high density lipoproteins. Curr Opin Lipidol 8: 181–188PubMedGoogle Scholar
  138. Rosano GM, Sarrel PM, Poole WP, Collins P (1993) Beneficial effect of oestrogen on exercise induced myocardial ischemia in women with coronary artery disease. Lancet 342: 133–136PubMedGoogle Scholar
  139. Rosenbaum M, Leibel RL, Hirsch JH (1997) Obesity. N Engl J Med 337: 396–406Google Scholar
  140. Ross R (1990). The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362: 801–809Google Scholar
  141. Ross R (1995) Cell biology of atherosclerosis. Ann Rev Physiol 57: 791–804Google Scholar
  142. Rouru J, Anttila L, Koskinen P, Penttila TA, Irjala K, Huupponen R, Koulu M (1997) Serum leptin concentrations in women with polycystic ovary syndrome. J Clin Endocrinol Metab 82: 1697–1700PubMedGoogle Scholar
  143. Sacks FM, Walsh BW (1994) Sex hormones and lipoprotein metabolism. Curr Opin Lipidol 5: 236–240PubMedGoogle Scholar
  144. Sacks FM, Gerhard M, Walsh BW (1995) Sex hormones, lipoproteins, and vascular reactivity. Curr Opin Lipidol 6: 161–166PubMedGoogle Scholar
  145. Sampson M, Kong C, Patel A, Unwin R, Jacobs HS (1996) Ambulatory blood pressure profiles and plasminogen activator inhibitor (PAI-1) activity in lean women with and without the polycystic ovary syndrome. Clin Endocrinol (Oxf) 45: 623–9Google Scholar
  146. Schmitz G, Orso E, Rothe G, Klucken J (1997) Scavenging, signalling and adhesion coupling in macrophages: implications for atherosclerosis. Curr Opin Lipidol 8: 287–300PubMedGoogle Scholar
  147. Scidell JC, Bjorntorp P, Sjostrom L, Kvist H, Sannerstedt R (1990) Visceral fat accumulation in men is positively associated with insulin, glucose, and C-peptide levels but negatively with testosterone levels. Metabolism 39: 897–901Google Scholar
  148. Sigler LH, Tuglan J (1943) Treatment of angina pectoris with testosterone propionate. NY St J Med 43: 1424–1428Google Scholar
  149. Sih R, Morley JE, Kaiser FE, Perry HM, Patrick P, and Ross C (1997) Testosterone replacement in older hypogonadal men: a 12 month randomized controlled trial. J Clin Endo-cinol Metab 82: 1661–1667Google Scholar
  150. Simon D, Charles MA, Nahoul K, Orssaud G, Kremski J, Hully V, Joubert E, Papoz L, Eschwege E (1997) Association between plasma total testosterone and cardiovascular risk factors in healthy adult men: the Telecom Study. J Clin Endocrinol Metab 82: 682–685PubMedGoogle Scholar
  151. Smith EB (1996) Haemostatic factors and atherogenesis. Atherosclerosis 124: 137–143PubMedGoogle Scholar
  152. Sobel MI, Winkel CA, Macy LB, Liao P, Bjornsson TD (1995) The regulation of plasminogen activators and plasminogen activator inhibitor type 1 in endothelial cells by sex hormones. Am J Obstetr Gynecol 173: 801–808Google Scholar
  153. Sorva R, Kuusi T, Taskinene MR, Perheentupa J, Nikkila EA (1988) Testosterone substitution increases the activity of lipoprotein lipase and hepatic lipase in hypogonadal men. Atherosclerosis 69: 191–197PubMedGoogle Scholar
  154. Stanick S, Dornfeld LP, Maxwell MH, Viosca A, Korenman SG (1981) The effect of weight loss on reproductive hormones in obese men. J Clin Endocrinol Metab 53: 828–832Google Scholar
  155. Statistisches Bundesamt (ed) (1997) Statistical year book 1997. Wiesbaden St. Clair RW (1997) Effects of estrogens on macrophage foam cells: a potential target for the protective effects of estrogens on atherosclerosis. Curr Opin Lipidol 8: 281–286Google Scholar
  156. Stein JH, Rosenson RS (1997) Lipoprotein Lp(a) excess and coronary heart disease. Arch Intern Med 157: 1170–1176PubMedGoogle Scholar
  157. Tabas I (1996) The stimulation of the cholesterol esterifcation pathway by atherogenic lipoproteins in macrophages. Curr Opin Lipidol 7: 260–268Google Scholar
  158. Tabas I (1997) Phospholipid metabolism in cholesterol loaded macrophages. Curr Opin Lipidol 8: 266–274Google Scholar
  159. Talbott E, Guzick D, Clerici A, Berga S, Detre K, Weimer K and Kuller L (1995) Coronary heart disease risk factors in women with polycystic ovary syndrome. Arterioscl Thromb Vase Biol 15: 821–6Google Scholar
  160. Tall AR (1993) Plasma cholesteryl ester transfer protein. J Lipid Res 34: 1255–1274PubMedGoogle Scholar
  161. Tall A (1995) Plasma lipid transfer enzymes. Ann Rev Biochem 64: 235–25PubMedGoogle Scholar
  162. Tang J, Srivastava RAK, Krul ES, Baumann D, Pfleger B A, Kitchens RT, Schonfeld G (1991) In vivo regulation of apolipoprotein A-I gene expression by estradiol and testosterone occurs by different mechanisms in inbred strains of mice. J Lipid Res 32: 1571–1585PubMedGoogle Scholar
  163. Tchernof A, Labrie F, Bélanger A, Després JP (1996) Obesity and metabolic complications: contribution of dehyroepiandrosterone and other steroid hormones. J Endocrinol 150 (Suppl): 155–164Google Scholar
  164. Tchernof A, Labrie F, Bélanger A, Prud’homme D, Bouchard C, Tremblay A, Nadeau A, Després JP (1997) Relationships between endogenous steroid hormone, sex hormone binding globulin and lipoprotein levels in men: contribution of visceral obesity, insulin levels and other metabolic variables. Atherosclerosis 133: 235–244PubMedGoogle Scholar
  165. The Expert Panel (1993) Summary of the second report of the National Cholesterol Education Programme on detection, evaluation, and treatment of high blood cholesterol in adults. (Adult Treatment Panel II). JAMA 269: 3015–3023Google Scholar
  166. Thompson PD, Cullinane EM, Sady SP, Chenevery C, Saritelli AL, Sady MA (1989) Contrasting effects of testosterone and stanozolol on serum lipoprotein levels JAMA 261: 1165–1168Google Scholar
  167. Thompson SG, Kienast J, Pyke SDM, Haverkate F, van de Loo JCW for the European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group (1995). Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. N Engl J Med 332: 635–641PubMedGoogle Scholar
  168. Toda T, Toda Y, Cho BH, Kummerow FA (1984) Ultrastructural changes in the comb and aorta of chicks fed excess testosterone. Atherosclerosis 51: 47–53PubMedGoogle Scholar
  169. Tomita T, Sawamura F, Uetsuka R, Chiba T, Miura S, Ikeda M, Tomita I (1996) Inhibition of cholesteryl ester accumulation by 17β-estradiol in macrophges through activation of neutral cholesterol esterase. Biochim Biophys Acta 1300: 210–218PubMedGoogle Scholar
  170. Velazquez EM, Mendoza SG, Wang P, Glueck CJ (1997) Metformin therapy is associated with a decrease in plasma plasminogen activator inhibitor 1, lipoprotein(a), and immu-noreactive insulin levels in patients with the polycystic ovary syndrome. Metabolism 46: 454–457PubMedGoogle Scholar
  171. Verheijen JH, Rijken DC, Chang GT, Preston FE, Kluft C (1984) Modulation of rapid plasmi-nogen activator inhibitor in plasma by stanozolol. Thromb Haemost 51: 396PubMedGoogle Scholar
  172. 397.
    Verheijen JH, Rijken DC, Chang GT, Preston FE, Kluft C (1984) Modulation of rapid plasmi-nogen activator inhibitor in plasma by stanozolol. Thromb Haemost 51: 396Google Scholar
  173. Vermeulen A (1996) Decreased androgen levels and obesity in men. Ann Medi 28: 13–15Google Scholar
  174. Vermeulen A, Kaufman JM (1995) Ageing of the hypothalamo-pituitary-testicular axis in men. Hor Res 43: 25–28Google Scholar
  175. Vogel G (1996) Leptin: a trigger for puberty? Science 274: 1466–1467PubMedGoogle Scholar
  176. Vogel RA (1997) Coronary risk factors, endothelial function, and atherosclerosis: a review. Clin Cardiol 20: 426–432PubMedGoogle Scholar
  177. von Eckardstein S, von Eckardstein A, Bender HG, Schulte H, Assmann G (1996) Elevated low density lipoprotein-cholesterol in women with polycystic ovary syndrome. J Gynecol Endocrin 10: 311–318Google Scholar
  178. von Eckardstein A, Kliesch S, Nieschlag E, Chirazi A, Assmann G, Behre HM (1997) Suppression of endogenous testosterone in young men increases serum levels of HDL-sub- class LpA-I and lipoprotein(a) J Clin Endocrinol Metab 82: 3367–3372Google Scholar
  179. von Eckardstein A, Büchter D, Kliesch S, Chirazi A, Nieschlag E, Assmann G, Behre HM (1998) Effects of testosterone suppression in young men by cetrorelix on plasma lipids, lipolytic enzymes, lipid transfer proteins, insulin, and leptin (submitted)Google Scholar
  180. Wild RA, Painter PC, Coulson PB, Carruth BK, Ranney GB (1985) Lipoprotein lipid concentrations and cardiovascular risk in women with the polycystic ovary syndrome. J Clin Endocrinol Metabol 61: 946–51Google Scholar
  181. Wild RA, Grubb B, Hartz MD, van Nort JJ, Bachman W, Bartholomew M (1990) Clinical signs of androgen excess as risk factors for coronary artery disease. Fertil Steril 54:255– 260Google Scholar
  182. Winkler UH (1996) Effects of androgens on haemostasis. Maturitas 24: 147–155PubMedGoogle Scholar
  183. Wortsman J, Soler NG (1982) Abnormalities of fuel metabolism in the polycystic ovary syndrome. Obstet Gynecol 60: 342–345PubMedGoogle Scholar
  184. Wu SZ, Weng XZ (1993) Therapeutic effects of an androgenic preparation on myocardial ischemia and cardiac function in 62 elderly male coronary heart disease patients. Chin Med J 106: 415–418PubMedGoogle Scholar
  185. Yang XC, Jing TY, Gesnick LM, Phillips GB (1993) Relation of hemostatic factors to other risk factors for coronary artery disease and to sex hormones in men. Arterioscler Thromb 13: 467–471PubMedGoogle Scholar
  186. Yarnell JWG, Beswick AD, Swetnam PM, Riad-Fahmy D (1993) Endogenous sex hormones and ischemic heart disease in men. The Caerphilly Prospective study. Arterioscler Thromb 13: 517–523Google Scholar
  187. Yoshida Y, Nakamura Y, Sugino N, Shimamura K, Ono M, Kato H (1996) Changes in inter- leukin 1 production of peritoneal macrophages during estrous cycle in golden hamsters. Endocrine J 43: 151–156Google Scholar
  188. Yue P, Chatterjee K, Beale C, Poole-Wilson PA, Collins P (1995) Testosterone relaxes rabbit coronary arteries and aorta. Circulation 91: 1154–1160PubMedGoogle Scholar
  189. Zgliczynski S, Ossowski M, Slowinska-Szrednicka J, Brzenzinska A, Zgliczynski W, Soszyns- ki P, Chotowska E, Szrednicki, M Sadowski, Z (1996) Effect of testosterone replacement therapy on lipids and lipoproteins in hypogonadal and elderly men. Atherosclerosis 121: 35–43PubMedGoogle Scholar
  190. Zhu XD, Bonet B, Knopp RH (1997) 17/? estradiol, progesterone, and testosterone inversely modulate low density lipoprotein oxidation and cytotoxicity in cultured placental tro- phoblast and macrophages. Am J Obstet Gynecol 177: 196–209Google Scholar
  191. Zimmerman GA, Mclntyre TM, Prescott SM (1996) Adhesion and signaling in vascular cell-cell interactions. J Clin Invest 98: 1699–1702PubMedGoogle Scholar
  192. Zmuda JM, Fahrenbach MC, Younkin BT (1993) The effect of testosterone aromatization on high density lipoprotein cholesterol levels and post-heparin lipolytic activity. Metabolism 39: 69–77Google Scholar
  193. Zmuda JM, Thompson PD, Dickenson R, Bausserman LL (1996) Testosterone decreases lipo-protein(a) in men. Am J Cardiol 77: 1244–1247Google Scholar

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© Springer-Verlag Berlin Heidelberg 1998

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  • Arnold von Eckardstein

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