We investigated whether a low plasma testosterone level is related to endothelial dysfunction in men with coronary risk factors. One hundred and eighty-seven consecutive male outpatients (mean age±SD: 47±15 years) who underwent measurement of flow-mediated vasodilation (FMD) of the brachial artery using ultrasonography were enrolled. The relationship between plasma hormones and FMD was analyzed. Total and free testosterone and dehydroepiandrosterone-sulfate (DHEA-S) were significantly correlated with %FMD (r=0.261, 0.354 and 0.295, respectively; p<0.001), while estradiol and cortisol were not. %FMD in the highest quartile of free testosterone was 1.7-fold higher than that in the lowest quartile. Multiple regression analysis revealed that total and free testosterone were related to %FMD independent of age, body mass index, hypertension, hyperlipidemia, diabetes mellitus and smoking (β=0.198 and 0.247, respectively; p<0.01), and were independent of age, body mass index, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, smoking and nitroglycerin-induced dilation (β=0.196 and 0.227, respectively; p<0.01). DHEA-S was not significantly related to %FMD in multivariate analysis. In conclusion, a low plasma testosterone level was associated with endothelial dysfunction in men independent of other risk factors, suggesting a protective effect of endogenous testosterone on the endothelium.
Lamberts SW, van den Beld AW, van der Lely AJ : The endocrinology of aging. Science 1997; 278: 419–424.
Muller M, den Tonkelaar I, Thijssen JH, Grobbee DE, van der Schouw YT : Endogenous sex hormones in men aged 40–80 years. Eur J Endocrinol 2003; 149: 583–589.
Kaufman JM, Vermeulen A : The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev 2005; 26: 833–876.
Hak AE, Witteman JC, de Jong FH, Geerlings MI, Hofman A, Pols HA : Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study. J Clin Endocrinol Metab 2002; 87: 3632–3639.
van den Beld AW, Bots ML, Janssen JA, Pols HA, Lamberts SW, Grobbee DE : Endogenous hormones and carotid atherosclerosis in elderly men. Am J Epidemiol 2003; 157: 25–31.
Feldman HA, Johannes CB, McKinlay JB, Longcope C : 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.
Simon D, Charles MA, Nahoul K, et al: Association between plasma total testosterone and cardiovascular risk factors in healthy adult men: the Telecom Study. J Clin Endocrinol Metab 1997; 82: 682–685.
Barrett-Connor E, Khaw KT : Endogenous sex hormones and cardiovascular disease in men. A prospective population-based study. Circulation 1988; 78: 539–545.
Fogari R, Preti P, Zoppi A, et al: Serum testosterone levels and arterial blood pressure in the elderly. Hypertens Res 2005; 28: 625–630.
Stellato RK, Feldman HA, Hamdy O, Horton ES, McKinlay JB : 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.
Rosano GM, Leonardo F, Pagnotta P, et al: Acute anti-ischemic effect of testosterone in men with coronary artery disease. Circulation 1999; 99: 1666–1670.
English KM, Steeds RP, Jones TH, Diver MJ, Channer KS : Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: a randomized, double-blind, placebo-controlled study. Circulation 2000; 102: 1906–1911.
Ong PJ, Patrizi G, Chong WC, Webb CM, Hayward CS, Collins P : Testosterone enhances flow-mediated brachial artery reactivity in men with coronary artery disease. Am J Cardiol 2000; 85: 269–272.
Kang SM, Jang Y, Kim JY, et al: Effect of oral administration of testosterone on brachial arterial vasoreactivity in men with coronary artery disease. Am J Cardiol 2002; 89: 862–864.
Japanese Society of Hypertension : Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2004). Hypertens Res 2006; 29 ( Suppl): S1–S105.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults : Related Articles, Links Free Full Text Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001; 285: 2486–2497.
American Diabetes Association : Screening for diabetes (Position statement). Diabetes Care 2001; 24 ( Suppl): S21–S24.
Hashimoto M, Eto M, Akishita M, et al: Correlation between flow-mediated vasodilatation of the brachial artery and intima-media thickness in the carotid artery in men. Arterioscler Thromb Vasc Biol 1999; 19: 2795–2800.
Tarutani Y, Matsumoto T, Takashima H, Yamane T, Horie M : Brachial artery flow-mediated vasodilation is correlated with coronary vasomotor and fibrinolytic responses induced by bradykinin. Hypertens Res 2005; 28: 59–66.
Raitakari OT, Celermajer DS : Flow-mediated dilatation. Br J Clin Pharmacol 2000; 50: 397–404.
Sewdarsen M, Vythilingum S, Jialal I, Desai RK, Becker P : Abnormalities in sex hormones are a risk factor for premature manifestation of coronary artery disease in South African Indian men. Atherosclerosis 1990; 83: 111–117.
Jeppesen LL, Jorgensen HS, Nakayama H, Raaschou HO, Olsen TS, Winther K : Decreased serum testosterone in men with acute ischemic stroke. Arterioscler Thromb Vasc Biol 1996; 16: 749–754.
Yarnell JW, Beswick AD, Sweetnam PM, Riad-Fahmy D : Endogenous sex hormones and ischemic heart disease in men. The Caerphilly prospective study. Arterioscler Thromb 1993; 13: 517–520.
Arnlov J, Pencina MJ, Amin S, et al: Endogenous sex hormones and cardiovascular disease incidence in men. Ann Intern Med 2006; 145: 176–184.
Feldman HA, Johannes CB, Araujo AB, Mohr BA, Longcope C, McKinlay JB : Low dehydroepiandrosterone and ischemic heart disease in middle-aged men: prospective results from the Massachusetts Male Aging Study. Am J Epidemiol 2001; 153: 79–89.
Trivedi DP, Khaw KT : Dehydroepiandrosterone sulfate and mortality in elderly men and women. J Clin Endocrinol Metab 2001; 86: 4171–4177.
Smith GD, Ben-Shlomo Y, Beswick A, Yarnell J, Lightman S, Elwood P : Cortisol, testosterone, and coronary heart disease: prospective evidence from the Caerphilly study. Circulation 2005; 112: 332–340.
Klee GG, Heser DW : Techniques to measure testosterone in the elderly. Mayo Clin Proc 2000; 75 ( Suppl): S19–S25.
Webb CM, McNeill JG, Hayward CS, de Zeigler D, Collins P : Effects of testosterone on coronary vasomotor regulation in men with coronary heart disease. Circulation 1999; 100: 1690–1696.
Chou TM, Sudhir K, Hutchison SJ, et al: Testosterone induces dilation of canine coronary conductance and resistance arteries in vivo. Circulation 1996; 94: 2614–2619.
Jones RD, Pugh PJ, Jones TH, Channer KS : The vasodilatory action of testosterone: a potassium-channel opening or a calcium antagonistic action? Br J Pharmacol 2003; 138: 733–744.
Liu PY, Death AK, Handelsman DJ : Androgens and cardiovascular disease. Endocr Rev 2003; 24: 313–340.
Yu J, Eto M, Akishita M, Kaneko A, Ouchi Y, Okabe T : Signaling pathway of nitric oxide production induced by ginsenoside Rb1 in human aortic endothelial cells: a possible involvement of androgen receptor. Biochem Biophys Res Commun 2007; 353: 764–769.
Kravariti M, Naka KK, Kalantaridou SN, et al: Predictors of endothelial dysfunction in young women with polycystic ovary syndrome. J Clin Endocrinol Metab 2005; 90: 5088–5095.
McCredie RJ, McCrohon JA, Turner L, Griffiths KA, Handelsman DJ, Celermajer DS : Vascular reactivity is impaired in genetic females taking high-dose androgens. J Am Coll Cardiol 1998; 32: 1331–1335.
Wakasugi M, Noguchi T, Kazama YI, Kanemaru Y, Onaya T : The effects of sex hormones on the synthesis of prostacyclin (PGI2) by vascular tissues. Prostaglandins 1989; 37: 401–410.
Liu PY, Christian RC, Ruan M, Miller VM, Fitzpatrick LA : Correlating androgen and estrogen steroid receptor expression with coronary calcification and atherosclerosis in men without known coronary artery disease. J Clin Endocrinol Metab 2005; 90: 1041–1046.
Christian RC, Liu PY, Harrington S, Ruan M, Miller VM, Fitzpatrick LA : Intimal estrogen receptor (ER)beta, but not ERalpha expression, is correlated with coronary calcification and atherosclerosis in pre- and postmenopausal women. J Clin Endocrinol Metab 2006; 91: 2713–2720.
Rights and permissions
About this article
Cite this article
Akishita, M., Hashimoto, M., Ohike, Y. et al. Low Testosterone Level Is an Independent Determinant of Endothelial Dysfunction in Men. Hypertens Res 30, 1029–1034 (2007). https://doi.org/10.1291/hypres.30.1029
- sex hormone
- risk factor
This article is cited by
Centenarian longevity had inverse relationships with nutritional status and abdominal obesity and positive relationships with sex hormones and bone turnover in the oldest females
Journal of Translational Medicine (2021)
Sex Differences in Cardiovascular Aging and Heart Failure
Current Heart Failure Reports (2020)
The Gut Microbiome and Men’s Sexual Health
Current Sexual Health Reports (2019)
Relationships of Sex Hormone Levels with Activity of Daily Living in Chinese Female Centenarians
The journal of nutrition, health & aging (2019)
Molecular mechanisms associated with diabetic endothelial–erectile dysfunction
Nature Reviews Urology (2016)