Abstract
Globally, cardiovascular disease is the single largest cause of mortality. The differences
in pattern of cardiovascular disease between the two genders have not been explained
properly. The spotlight has largely been focused on estrogens but no conclusive evidence
has proven its role in reducing the incidence of cardiovascular disease. Consequently,
androgens have attracted significant interest in explaining the gender difference
in cardiovascular disease. More studies in last two decades have increased our knowledge
about the effects of androgens on cardiovascular disease progression. Evidence for
age related fall in testosterone levels in males and increasing cardiovascular events
with age had lead to the postulation of idea of ‘andropause or male menopause’. Unfortunately,
for the last few decades the androgens have been highlighted as agents of abuse among
athletes all over the world. There have been multiple reports of their association
with sudden cardiac death and adverse cardiovascular outcomes when abused. Contrastingly,
there has been an increasing prescription use of testosterone supplementation in various
conditions related to androgen deficiency state and for many other off-label indications.
Human observational studies have mostly concluded that men with lower testosterone
levels tend to have higher incidence of coronary artery disease. Emerging evidence
supports that lower androgen levels predict poor cardiovascular risk profile. Role
with supplementation of testosterone for cardiovascular disease is being studied in
both primary and secondary prevention stages and its safety being evaluated. This
is an appropriate time to review the role of androgens specifically from a cardiovascular
standpoint.
Abbreviations:
CAD (Coronary artery disease), CVD (Cardiovascular disease), DHEA (Dehydroepiandrosterone), SHBG (Sex hormone binding globulin), IMT (Intima media thickness), FMD (Flow mediated dilatation)Keywords
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References
- The global burden of disease.World Health Organization, Geneva1996
- Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group.JAMA. 1998; 280: 605-613
- Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial.JAMA. 2002; 288: 321-333
- Initial findings leading to modifications of its research protocol.JAMA. 1970; 214: 1303-1313
- Risks of testosterone-replacement therapy and recommendations for monitoring.N Engl J Med. 2004; 350: 482-492
- The analog free testosterone assay: are the results in men clinically useful?.Clin Chem. 1998; 44: 2178-2182
- Evaluation of assays available to measure free testosterone.Metabolism. 2002; 51: 554-559
- Techniques to measure testosterone in the elderly.Mayo Clin Proc. 2000; 75: S19-S25
- Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study.J Clin Endocrinol Metab. 2002; 87: 589-598
- Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging.J Clin Endocrinol Metab. 2001; 86: 724-731
- The World Health Report. World Health Organization, Geneva2002
- The sex differential in mortality from all causes and ischemic heart disease.Am J Epidemiol. 1983; 117: 165-172
- Endogenous sex hormones and cardiovascular disease in men. A prospective population-based study.Circulation. 1988; 78: 539-545
- Are low dehydroepiandrosterone sulphate levels predictive for cardiovascular diseases? A review of prospective and retrospective studies.Acta Cardiol. 2003; 58: 403-410
- Low dehydroepiandrosterone sulfate and heart disease in middle-aged men: cross-sectional results from the Massachusetts Male Aging Study.Ann Epidemiol. 1998; 8: 217-228
- Dehydroepiandrosterone, dehydroepiandrosterone sulphate and cardiovascular disease.J Endocrinol. 1996; 150: S149-S153
- Dehydroepiandrosterone sulfate does not predict cardiovascular death in postmenopausal women. The Rancho Bernardo Study.Circulation. 1995; 91: 1757-1760
- Androgens and diabetes in men: results from the Third National Health and Nutrition Examination Survey (NHANES III).Diabetes Care. 2007; 30: 234-238
- Low levels of sex hormone-binding globulin and testosterone predict the development of non-insulin-dependent diabetes mellitus in men. MRFIT Research Group. Multiple Risk Factor Intervention Trial.Am J Epidemiol. 1996; 1: 889-897
- Testosterone, sex hormone-binding globulin, and the development of type 2 diabetes in middle-aged men: prospective results from the Massachusetts male aging study.Diabetes Care. 2000; 23: 490-494
- Rancho Bernardo Study. Endogenous sex hormones and the development of type 2 diabetes in older men and women: the Rancho Bernardo study.Diabetes Care. 2002; 25: 55-60
- Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men.Diabetes Care. 2004; 27: 1036-1041
- Low sex hormone-binding globulin, total testosterone, and symptomatic androgen deficiency are associated with development of the metabolic syndrome in nonobese men.J Clin Endocrinol Metab. 2006; 91: 843-850
- Hypoandrogen-metabolic syndrome: a potentially common and underdiagnosed condition in men.Int J Clin Pract. 2007; 61: 341-344
- Endogenous sex hormones, high density lipoprotein cholesterol, and other lipoprotein fractions in men.Arterioscler Thromb. 1991; 11: 489-494
- Relation between plasma high-density lipoprotein cholesterol and sex hormone concentrations in men.Am J Cardiol. 1984; 53: 1259-1263
- Plasma testosterone, high density lipoprotein cholesterol and other lipoprotein fractions.Am J Cardiol. 1981; 48: 897-902
- Relationship of sex hormones to lipids and lipoproteins in nondiabetic men.J Clin Endocrinol Metab. 1993; 77: 1610-1615
- Differential contribution of testosterone and estradiol in the determination of cholesterol and lipoprotein profile in healthy middle-aged men.Atherosclerosis. 2003; 166: 95-102
- Low levels of sex hormone-binding globulin and testosterone are associated with smaller, denser low density lipoprotein in normoglycemic men.J Clin Endocrinol Metab. 1996; 81: 3697-3701
- Longitudinal relation between endogenous testosterone and cardiovascular disease risk factors in middle-aged men. A 13-year follow-up of former Multiple Risk Factor Intervention Trial participants.Am J Epidemiol. 1997; 146: 609-617
- Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials.Mayo Clin Proc. 2007; 82: 29-39
- Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study.J Clin Endocrinol Metab. 2002 Aug; 87: 3632-3639
- Androgen receptor expression is greater in macrophages from male than from female donors. A sex difference with implications for atherogenesis.Circulation. 2000; 101: 224-226
- Testosterone (T) enhances apoptosis-related damage in human vascular endothelial cells.Endocrinology. 2002; 143: 1119-1125
- Androgen receptors, 5 alpha-reductase activity and androgen-dependent proliferation of vascular smooth muscle cells.J Steroid Biochem Mol Biol. 1994; 50: 169-174
- Estrogen inhibits cuff-induced intimal thickening of rat femoral artery: effects on migration and proliferation of vascular smooth muscle cells.Atherosclerosis. 1997; 130: 1-10
- Endogenous sex hormones and progression of carotid atherosclerosis in elderly men.Circulation. 2004; 4: 2074-2079
- Men with coronary artery disease have lower levels of testosterone than those with normal coronary angiograms.Eur Heart J. 2000; 21: 890-895
- Androgen deprivation in males is associated with decreased central arterial compliance and reduced central systolic blood pressure.J Hum Hypertens. 2000; 14: 395-397
- Natural androgens inhibit male atherosclerosis: a study in castrated, cholesterol-fed rabbits.Circ Res. 1999; 84: 813-819
- Effect of testosterone on atherogenesis in cholesterol-fed rabbits with similar plasma cholesterol levels.Atherosclerosis. 1993; 99: 79-86
- Relationship between testosterone and indexes indicating endothelial function in male coronary heart disease patients.Asian J Androl. 2008; 10: 214-218
- The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men.J Clin Endocrinol Metab. 2004; 89: 3313-3318
- Association of endogenous sex hormone with C-reactive protein levels in middle-aged and elderly men.Clin Endocrinol. 2007; 66: 394-398
- Sex hormone-binding globulin and serum testosterone are inversely associated with C-reactive protein levels in postmenopausal women at high risk for cardiovascular disease.Ann Epidemiol. 2006; 16: 105-112
- High-sensitivity C-reactive protein is independently associated with early carotid artery progression in women but not in men: the INVADE Study. INVADE Study Group.Stroke. 2007; 38: 2881-2886
- Steroid sex hormones for lower limb atherosclerosis.Cochrane Database Syst Rev. 2002; 1: CD000188
Webb CM, Adamson DL, de Zeigler D, et al. Effect of acute testosterone on myocardial ischemia in men with coronary artery disease. Am J Cardiol. 1999;83(3):437–9, A9.
- Acute anti-ischemic effect of testosterone in men with coronary artery disease.Circulation. 1999; 99: 1666-1670
- Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life.Heart. 2004; 90: 871-876
- Effects of testosterone on coronary vasomotor regulation in men with coronary heart disease.Circulation. 1999; 100: 1690-1696
- Testosterone induces dilation of canine coronary conductance and resistance arteries in vivo.Circulation. 1996; 94: 2614-2619
- Brief exposure to exogenous testosterone increases death signaling and adversely affects myocardial function after ischemia.Am J Physiol Regul Integr Comp Physiol. 2006; 290: R1168-R1174
- Long-term and immediate effect of testosterone on single T-type calcium channel in neonatal rat cardiomyocytes.Endocrinology. 2006; 147: 5160-5169
- Effect of intravenous testosterone on myocardial ischemia in men with coronary artery disease.Am Heart J. 2002; 143: 249-256
- Effect of testosterone cypionate on postexercise ST segment depression.Br Heart J. 1977; 39: 1217-1222
- Effects of oral testosterone treatment on myocardial perfusion and vascular function in men with low plasma testosterone and coronary heart disease.Am J Cardiol. 2008; 101: 618-624
- Prevalence of hypertension in the US adult population. Results from the Third National Health and Nutrition Examination Survey,1988–1991.Hypertension. 1995; 25: 305-313
- Blood pressure and endogenous testosterone in men: an inverse relationship.J Hypertens. 1988; 6: 329-332
- Serum testosterone levels and arterial blood pressure in the elderly.Hypertens Res. 2005; 28: 625-630
- Effects of first-line antihypertensive agents on sexual function and sex hormones.J Hypertens Suppl. 1988; 6: S649-S651
- Sex hormones and hypertension.Cardiovasc Res. 2002; 53: 688-708
- Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study.J Clin Endocrinol Metab. 1991; 73: 1016-1025
- Sexual activity and plasma testosterone levels in hypertensive males.Am J Hypertens. 2002; 15: 217-221
- Gender differences in hypertension in spontaneously hypertensive rats: role of androgens and androgen receptor.Hypertension. 1999; 34: 920-923
- Spontaneously hypertensive rat Y chromosome increases indexes of sympathetic nervous system activity.Hypertension. 1997; 29: 613-618
- Gonadal effects on plasma ACE activity in mice.Atherosclerosis. 2002; 160: 311-316
- Gender differences in cardiac ACE expression are normalized in androgen-deprived male mice.Am J Physiol Heart Circ Physiol. 2002; 283: H1997-H2003
- Anabolic steroids induce cardiac renin–angiotensin system and impair the beneficial effects of aerobic training in rats.Am J Physiol Heart Circ Physiol. 2007; 293: H3575-H3583
- Gender differences in development of hypertension in spontaneously hypertensive rats: role of the renin–angiotensin system.Hypertension. 2000; 35: 480-483
- Expression of adrenal cytochromes P-450 in testosterone-induced hypertension.Hypertension. 1991; 18: 523-528
- Testosterone acts as a coronary vasodilator by a calcium antagonistic action.J Endocrinol Invest. 2002; 25: 455-458
- Testosterone-induced relaxation of rat aorta is androgen structure specific and involves K+ channel activation.J Appl Physiol. 2001; 91: 2742-2750
- Vascular reactivity in hypogonadal men is reduced by androgen substitution.J Clin Endocrinol Metab. 2002; 87: 5030-5037
- Gender differences in cardiac remodeling secondary to chronic volume overload.J Card Fail. 2002; 8: 101-107
- Androgen receptors mediate hypertrophy in cardiac myocytes.Circulation. 1998; 98: 256-261
- Anabolic steroids induce cardiac renin–angiotensin system and impair the beneficial effects of aerobic training in rats.Am J Physiol Heart Circ Physiol. 2007; 293: H3575-H3583
- Effects of testosterone on cytokines and left ventricular remodeling following heart failure.Cell Physiol Biochem. 2007; 20: 847-852
- Testosterone is required for delayed cardioprotection and enhanced heat shock protein 70 expression induced by preconditioning.Endocrinology. 2006; 147: 4569-4577
- Testosterone induces cytoprotection by activating ATP-sensitive K+ channels in the cardiac mitochondrial inner membrane.Circulation. 2004; 110: 3100-3107
- Acute actions of testosterone on contractile function of isolated rat ventricular myocytes.Eur J Endocrinol. 2005; 152: 479-483
- Testosterone therapy for men with chronic congestive heart failure.in: Program of the 84th Annual Meeting of The Endocrine Society, San Francisco, CA. 2002: 144
- Effects of testosterone and nandrolone on cardiac function: a randomized, placebo-controlled study.Clin Endocrinol (Oxf). 2007; 66: 235-245
- Prospective echocardiographic assessment of androgenic–anabolic steroids effects on cardiac structure and function in strength athletes.Int J Sports Med. 2003; 24: 344-351
- Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial.Eur Heart J. 2006; 27: 57-64
- Study protocol to investigate the effects of testosterone therapy as an adjunct to exercise rehabilitation in hypogonadal males with chronic heart failure.BM C Cardiovasc Disord. 2006; 30: 46
- Randomized placebo-controlled trial of androgen effects on muscle and bone in men requiring long-term systemic glucocorticoid treatment.J Clin Endocrinol Metab. 2003; 88: 3167-3176
- An acute myocardial infarction occurring in an anabolic steroid user.Med Sci Sports Exerc. 1994; 26: 408-413
- Atrial fibrillation and anabolic steroid abuse.Int J Cardiol. 2007; 117: e86-e87
- The effect of pharmacokinetically guided acute intravenous testosterone administration on electrocardiographic and blood pressure variables.J Clin Pharmacol. 1999; 39: 1038-1043
- Steroid abuse by athletes in a metropolitan area.Phys Sports Med. 1984; 12: 69-74
- Ethical authorship and publishing.Int J Cardiol. 2009; 131: 149-150
Article info
Publication history
Published online: November 18, 2009
Accepted:
October 18,
2009
Received:
September 3,
2009
Identification
Copyright
© 2009 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
