Copyright © 2000 by the European Society of Cardiology.
Men with coronary artery disease have lower levels of androgens than men with normal coronary angiograms
a Department of Cardiology, Royal Hallamshire Hospital, Sheffield
b Department of Human Metabolism and Clinical Biochemistry, University of Sheffield, Sheffield
c Department of Clinical Chemistry, Royal Liverpool University Hospital, Liverpool, U.K.
revised June 16, 1999; accepted June 30, 1999
Abstract
Aims High androgen levels are presumed by many to explain the male predisposition to coronary artery disease. However, natural androgens inhibit male atherosclerosis[1]. Our aim was to determine whether levels of androgens differ between men with and without coronary artery disease.
Methods and Results Ninety male subjects (60 with positive, and 30 with negative coronary angiograms) were recruited. Early morning, fasting blood samples were taken from each patient and free, total and bioavailable testosterone, sex hormone binding globulin, oestradiol, and lipids were measured. Bioavailable testosterone was assayed using a modified technique. Free androgen index was calculated. Men with coronary artery disease had significantly lower levels of free testosterone (mean (standard deviation)); 47·95 (13·77) vs 59·87 (26·05)pmol.l–1,P =0·027), bioavailable testosterone; 2·55 (0·77) vs 3·26 (1·18)nmol.l–1, P=0·005 and free androgen index; 37·8 (10·4) vs 48·47 (18·3), P=0·005, than controls. After controlling for differences in age and body mass index the differences in free androgen index and bioavailable testosterone remained statistically significant (P=0·008 and P=0·013, respectively).
Conclusion Men with coronary artery disease have significantly lower levels of androgens than normal controls, challenging the preconception that physiologically high levels of androgens in men account for their increased relative risk for coronary artery disease.
Key Words: Androgens, gender, coronary artery disease, sex hormones
f1 Correspondence: Dr Kevin S. Channer, Department of Cardiology, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, U.K.
References
- Alexandersen P, Haarbo J, Byrjalsen I, Lawaetz H, Christiansen C. Natural androgens inhibit male atherosclerosis: A study in castrated, cholesterol fed rabbits. Circ Res. 1999;84:813–819
[Abstract/Free Full Text] - British Heart Foundation Statistics Database, BHF, 1996, 21, 2
- Kannel WB, Hjortland MC, McNamara PM, Gordon T. Menopause and the risk of cardiovascular disease. The Framingham Study. Ann Intern Med. 1976;85:447–452[ISI][Medline]
- Stampfer MJ, Colditz GA, Willett WC. Post menopausal estrogen therapy and cardiovascular disease. N Engl J Med. 1991;325:756–762[Abstract]
- Heller R, Wheeler MJ, Micallef J. Relationship of HDL cholesterol with total and free testosterone and SHBG. Acta Endocrinologica. 1983;194:253–256
- Phillips GB, Jing TY, Resnick LM, Barbagallo M, Laragh JH, Sealey JE. Sex hormones and haemostatic risk factors for coronary heart disease in men with hypertension. J Hypertens. 1993;11:699–702[CrossRef][ISI][Medline]
- Zumoff B, Strain GS, Miller LK. Plasma free and non sex hormone binding globulin bound testosterone are decreased in obese men in proportion to their degree of obesity. J Clin Endocrinol Metab. 1990;71:929–931[Abstract]
- Haffner SM, Karhapaa P, Mykkanen L, Laakso M. Insulin Resistance, body fat distribution and sex hormones in men. Diabetes. 1994;43:212–219[Abstract]
- Glueck CJ, Glueck HI, Stroop D, Spiers J, Hamer T, Tracy T. Endogenous testosterone, fibrinolysis and coronary heart disease risk in hyperlipidaemic men. J Lab Clin Med. 1993;122:412–420[ISI][Medline]
- Stigler LH, Tulgan J. Treatment of angina pectoris by testosterone propionate. NY State J Med. 1943;43:1424–1428
- Rosano GMC, Leonardo F, Pagnotta P. Acute anti-ischaemic effect of testosterone in men with coronary artery disease. Circulation. 1999;99:1666–1670
[Abstract/Free Full Text] - Yue P, Chatterjee K, Beale C, Poole-Wilson, Collins P. Testosterone Relaxes Rabbit Coronary Arteries and aorta. Circulation. 1995;91:1154–1160
[Abstract/Free Full Text] - Webb CM, Adamson DL, de Zeigler D, Collins P. Effects of testosterone on coronary vasomotor regulation in men with coronary heart disease. Circulation. 1999;100:1690–1696
[Abstract/Free Full Text] - Cauley JA, Gutai JP, Kuller LH, Dai WS. Usefulness of sex steroid hormone levels in predicting coronary artery disease in men. Am J Cardiol. 1987;60:771–777[CrossRef][ISI][Medline]
- Barrett-Connor E, Khaw KT. Endogenous sex hormones and cardiovascular disease in men. A prospective population based study. Circulation. 1988;78:539–545
[Abstract/Free Full Text] - Yarnell JW, Beswick AD, Sweetnam PM, Riad-Fahmy D. Endogenous sex hormones and ischaemic heart disease in men. The Caerphilly Heart Study. Arterioscler Thromb Vasc Biol. 1993;13:517–520
[Abstract/Free Full Text] - Dunn JF, Nisula BC, Rodbard D. Transport of steroid hormones: Binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid binding globulin in human plasma. J Clin Endocrinol Metab. 1981;53:58–68[Abstract]
- Tremblay RR, Dube JY. Plasma concentrations of free and non Te-BG bound testosterone in women on oral contraceptives. Contraception. 1974;10:599–605[CrossRef][ISI][Medline]
- Kaufman JM, Vermeulen A. Declining gonadal function in elderly men. Baillieres Clin Endocrinol Metab. 1997;11:289–309[CrossRef][ISI][Medline]
- Schneider G, Kirschner MA, Berkowitz R, Ertel NH. Increased estrogen production in obese men. J Clin Endocrinol Metab. 1979;48:633–638[Abstract]
- Jockenhovel F, Blum WF, Vogel E. Testosterone substitution normalizes elevated serum leptin levels in hypogonadal men. J Clin Endocrinol Metab. 1997;82:2510–2513
[Abstract/Free Full Text] - Travia D, Tosi F, Negri C, Faccini G, Moghetti P, Muggeo M. Sustained therapy with 3-Hydroxy-3-methylglutaryl-coenzyme-A Reductase inhibitors does not impair steroidogenesis by adrenals and gonads. J Clin Endocrinol Metab. 1995;80:836–840[Abstract]
- Tenover JS. Effects of testosterone supplementation in the aging male. J Clin Endocrinol Metab. 1992;75:1092–1098[Abstract]
- Davidson JM, Chen JJ, Crapo L, Gray GD, Greenleaf WJ, Catania JA. Hormonal changes and sexual function in aging men. J Clin Endocrinol Metab. 1983;57:71–77[Abstract]
- Hajjar RR, Kaiser FE, Morley JE. Outcomes of long term testosterone replacement in older hypogonadal males: A retrospective analysis. J Clin Endocrinol Metab. 1997;82:3793–3796
[Abstract/Free Full Text]
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