Testosterone and the cardiovascular system: a comprehensive review of the clinical literature.
Authors:
Journal: Journal of the American Heart Association
Publication Type: Journal Article
Date: 2013
DOI: PMC3886770
ID: 24242682
Chemical List
- Biomarkers|||Testosterone
Reference List
- Araujo AB, O'Donnell AB, Brambilla DJ, Simpson WB, Longcope C, Matsumoto AM, McKinlay JB. Prevalence and incidence of androgen deficiency in middle‐aged and older men: estimates from the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 2004; 89:5920-5926|||Cunningham GR, Matsumoto AM, Swerdloff R. Low testosterone and men's health. J Clin Endocrinol Metab. 2004; 89|||Kalyani RR, Gavini S, Dobs A. Male hypogonadism in systemic disease. Endocrinol Metab Clin North Am. 2007; 36:333-348|||Spratt DI, Cox P, Orav J, Moloney J, Bigos T. Reproductive axis suppression in acute illness is related to disease severity. J Clin Endocrinol Metab. 1993; 76:1548-1554|||Beattie MC, Chen H, Fan J, Papadopoulos V, Miller P, Zirkin BR. Aging and luteinizing hormone effects on reactive oxygen species (ROS) production and DNA damage in rat Leydig cells. Biol Reprod. 2013; 88:10010.1095/biolreprod.112.107052|||Bassil N, Alkaade S, Morley J. The benefits and risks of testosterone replacement therapy: a review. Ther Clin Risk Manag. 2009; 5:427-448|||Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. 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|||Ferrini RL, Barrett‐Connor E. Sex hormones and age: a cross sectional study of testosterone and estradiol and their bioavailable fractions in community‐dwelling men. Am J Epidemiol. 1998; 147:750-754|||Tenover JS, Matsumoto AM, Plymate SR, Bremmer WJ. The effects of aging in normal men on bioavailable testosterone and luteinizing hormone secretion: response to clomiphene citrate. J Clin Endocrinol Metab. 1987; 65:1118-1126|||Bremner WJ, Vitiello MV, Prinz PN. Loss of circadian rhythmicity in blood testosterone levels with aging in normal men. J Clin Endocrinol Metab. 1983; 56:1278-1281|||Purifoy FE, Koopmans LH, Mayes DM. Age differences in serum androgen levels in normal adult males. Hum Biol. 1981; 53:499-511|||Pirke KM, Doerr P. Ages related changes in free plasma testosterone, dihydrotestosterone and oestradiol. Acta Endocrinol. 1975; 80:171-178|||Zhao SP, Li XP. The association of low plasma testosterone level with coronary artery disease in Chinese men. Int J Cardiol. 1998; 63:161-164|||English KM, Mandour O, Steeds RP, Diver MJ, Jones TH, Channer KS. Men with coronary artery disease have lower levels of androgens than men with normal coronary angiograms. Eur Heart J. 2000; 21:890-894|||Dobrzycki S, Serwatka W, Nadlewski S, Korecki J, Jackowski R, Paruk J, Ladny J, Hirnle T. An assessment of correlations between endogenous sex hormone levels and the extensiveness of coronary heart disease and the ejection fraction of the left ventricle in males. J Med Invest. 2003; 50:162-169|||Akishita M, Hashimoto M, Ohike Y, Ogawa S, Iijima K, Eto M, Ouchi Y. Low testosterone level as a predictor of cardiovascular events in Japanese men with coronary risk factors. Atherosclerosis. 2010; 210:232-236|||Rosano G, Sheiban I, Massaro R, Pgnotta P, Marazzi G, Vitale C, Mercuro G, Volterrani M, Aversa A, Fini M. Low testosterone levels are associated with coronary artery disease in male patients with angina. Int J Impot Res. 2007; 19:176-182|||Hu X, Rui L, Zhu T, Xia H, Yang X, Wang X, Liu H, Lu Z, Jiang H. Low testosterone level in middle‐aged male patients with coronary artery disease. Eur J Intern Med. 2011; 22:133-136|||Cauley JA, Gutai JP, Kuller LH, Dai WS. Usefulness of sex steroid hormones levels in predicting coronary artery disease in men. Am J Cardiol. 1987; 60:771-777|||Barrett‐Connor E, Khaw KT. Endogenous sex hormones and cardiovascular disease in men. A prospective population‐based study. Circulation. 1988; 78:539-545|||Kabakci G, Yildirir A, Can I, Unsal I, Erbas B. Relationship between endogenous sex hormones levels, lipoproteins, and coronary atherosclerosis in men undergoing coronary angiography. Cardiology. 1999; 92:221-225|||Arnlov J, Pencina MJ, Amin S, Nam BH, Benjamin EJ, Murabito JM, Wang TJ, Knapp PE, D'Agostino RB, Bhasin S, Vasan R. Endogenous sex hormones and cardiovascular disease incidence in men. Ann Intern Med. 2006; 145:176-184|||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|||Vermeulem A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999; 84:3666-3672|||Ding EL, Song Y, Malik VS, Liu S. Sex differences of endogenous sex hormones and risk of type 2 diabetes. JAMA. 2006; 295:1288-1299|||Corona G, Monami M, Rastrelli G, Aversa A, Sforza A, Lenzi A, Forti G, Mannucci E, Maggi M. Type 2 diabetes mellitus and testosterone: a meta‐analysis study. Int J Androl. 2010; 34:528-540|||Ohlsson C, Barrett‐Connor E, Bhasin S, Orwoll E, Labrie F, Karlsson M, Ljunggren O, Vandenput L, Mellstrom D, Tivesten A. High serum testosterone is associated with reduced risk of cardiovascular events in elderly men. The MrOS (Osteoporotic fractures in men) study in Sweden. J Am Coll Cardiology. 2011; 58:1674-1682|||Mulligan T, Frick MF, Zuraw QC, Stemhagen A, McWhirter C. Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract. 2006; 60:762-769|||Li L, Guo CY, Jia EZ, Zhu TB, Wang LS, Cao KJ, Ma WZ, Yang ZJ. Testosterone is negatively associated with the severity of coronary atherosclerosis in men. Asian J Androl. 2012; 14:875-878|||Phillips GB, Pinkernell BH, Jing TY. The association of hypotestosteronemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol. 1994; 14:701-706|||Haddad R, Kennedy C, Caples S, Tracz M, Bolona E, Sideras K, Uraga M, Erwin P, Montori V. Testosterone and cardiovascular risk in men: a systemic review and meta‐analysis of randomized placebo‐controlled trials. Mayo Clin Proc. 2007; 81:29-39|||Makinen J, Jarvisalo M, Pollanen P, Perheentupa A, Irjala K, Koskenvuo M, Makinen J, Huhtaniemi I, Raitakari O. Increased carotid atherosclerosis in andropausal middle‐aged men. J Am Coll Cardiol. 2005; 45:1603-1608|||Gray A, Feldman HA, McKinley JB, Longscope C. 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|||Feldman HA, Longscope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, Bremmer WJ, McKinlay JB. 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|||Haring R, Volzke H, Steveling A, Krebs A, Felix SB, Schofl C, Dorr M, Nauck M, Wallaschofski H. Low serum testosterone levels are associated with increased risk of mortality in a population‐based cohort of men aged 20‐79. Eur Heart J. 2010; 31:1494-1501|||Khaw KT, Dowsett M, Folkerd E, Bingham S, Wareham N, Luben R, Welch A, Day N. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC‐Norfolk) Prospective Population Study. Circulation. 2007; 116:2694-2701|||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|||Araujo AB, Kupelian V, Page ST, Handelsman DJ, Bremmer WJ, McKinlay JB. Sex steroids and all‐cause and cause‐specific mortality in men. Arch Intern Med. 2007; 167:1252-1260|||Menke A, Guallar E, Rohrmann S, Nelson WG, Rifai N, Kanarek N, Feinleib M, Michos ED, Dobs A, Platz EA. Sex steroid hormone concentrations and risk of death in US men. Am J Epidemiol. 2010; 171:583-592|||Vikan T, Schirmer H, Njolstad I, Svartberg J. Endogenous sex hormones and the prospective association with cardiovascular disease and mortality in men: the Tromso Study. Eur J Endocrinol. 2009; 161:435-442|||Araujo AB, Dixon JM, Suarez EA, Murad MH, Guey LT, Wittert GA. Endogenous testosterone and mortality in men: a systemic review and meta‐analysis. J Clin Endocrinol Metab. 2011; 96:3007-3019|||Tivesten A, Vandenput L, Labrie F, Karlsson MK, Ljunggren O, Mellstrom D, Ohlsson C. Low serum testosterone and estradiol predict mortality in elderly men. J Clin Endocrinol Metab. 2009; 94:2482-2488|||Szulc P, Claustrat B, Delmas PD. Serum concentrations of 17β‐E2 and 25‐hydroxycholecalciferol (25OHD) in relation to all‐cause mortality in older men: the MINOS study. Clin Endocrinol (Oxf). 2009; 71:594-602|||Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR. Low serum testosterone and mortality in male veterans. Arch Intern Med. 2006; 166:1660-1665|||Lehtonen A, Huupponen R, Tuomilehto J, Lavonius S, Arve S, Isoaho H, Huhtaniemi I, Tilvis R. Serum testosterone but not leptin predicts mortality in elderly men. Age Ageing. 2008; 37:461-464|||Laughlin GA, Barrett‐Connor E, Bergstrom J. Low serum testosterone and mortality in older men. J Clin Endocrinol Metab. 2008; 93:68-75|||Malkin CJ, Pugh PJ, Morris PD, Asif S, Jones TH, Channer KS. Low serum testosterone and increased mortality in men with coronary heart disease. Heart. 2010; 96:1821-1825|||Lesser MA. Testosterone propionate therapy in one hundred cases of angina pectoris. J Clin Endocrinol Metab. 1946; 6:549-557|||Levine SA, Likoff WB. The therapeutic value of testosterone propionate in angina pectoris. N Engl J Med. 1943; 229:770-772|||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|||Rosano GM, Leonardo F, Pagnotta P, Pelliccia F, Panina G, Cerquetani E, della Monica PL, Bonfigli B, Volpe M, Chierchia SL. Acute anti‐ischemic effect of testosterone in men with coronary artery disease. Circulation. 1999; 99:1666-1670|||Webb CM, Adamson DL, de Zeigler D, Collins P. Effect of acute testosterone on myocardial ischemia in men with coronary artery disease. Am J Cardiol. 1999; 83:437-439|||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|||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, Chung N, Cho SY, Chae JS, Lee JH. Effect of oral administration of testosterone on brachial arterial vasoreactivity in men with coronary artery disease. Am J Cardiol. 2002; 89:862-864|||Worboys S, Kotsopoulos D, Teede H, McGrath B, Davis SR. Evidence that parenteral testosterone therapy may improve endothelium‐dependent and ‐independent vasodilation in postmenopausal women already receiving estrogen. J Clin Endocrinol Metab. 2001; 86:158-161|||Yue P, Chatterjee K, Beale C, Poole‐Wilson PA, Collins P. Testosterone relaxes rabbit coronary arteries and aorta. Circulation. 1995; 91:1154-1160|||Chou TM, Sudhir K, Hutchison SJ, Ko E, Amidon TM, Collins P, Chatterjee K. Testosterone induces dilation of canine coronary conductance and resistance arteries in vivo. Circulation. 1996; 94:2614-2619|||O'Connor EK, Ivey JR, Bowles DK. Differential effects of androgens on coronary blood flow regulation and arteriolar diameter in intact and castrated swine. Biol Sex Differ. 2012; 3:10.|||Scragg JL, Jones RD, Channer KS, Jones TH, Peers C. Testosterone is a potent inhibitor of L‐type Ca2+ channels. Biochem Biophys Res Commun. 2004; 318:503-506|||Cairrao E, Santos‐Silva AJ, Verde I. PKG is involved in testosterone‐induced vasorelaxation of human umbilical artery. Eur J Pharmacol. 2010; 640:94-101|||Daubresse JC, Meunier JC, Wilmotte J, Luyckx AS, Lefebvre PJ. Pituitary‐testicular axis in diabetic men with and without sexual impotence. Diabetes Metab. 1978; 4:233-237|||Shahwan MM, Spathis GS, Fry DE, Wood PJ, Marks V. Differences in pituitary and testicular function between diabetic patients on insulin and oral anti‐diabetic agents. Diabetologia. 1978; 15:13-17|||Colangelo LA, Ouyang P, Liu K, Kopp P, Golden SH, Dobs A, Szklo M, Vaidya D, Cushman M, Gapstur SM. Association of endogenous sex hormones with diabetes and impaired fasting glucose in men. Diabetes Care. 2009; 32:1049-1051|||Laaksonen DE, Niskanen L, Punnonen K, Nyyssonen K, Tuomainen TP, Valkonen VP, Salonen R, Salonen JT. Testosterone and sex hormone‐binding globulin predict the metabolic syndrome and diabetes in middle‐aged men. Diabetes Care. 2004; 27:1036-1041|||Vikan T, Schirmer H, Njolstad I, Svartberg J. Low testosterone and sex hormone‐binding globulin levels and high estradiol levels are independent predictors of type 2 diabetes in men. Eur J Endocrinol. 2010; 162:747-754|||Keating NL, O'Malley AJ, Freeland SJ, Smith MR. Diabetes and cardiovascular disease during androgen deprivation therapy: observational study of veterans with prostate cancer. J Natl Cancer Inst. 2010; 102:39-46|||Jones TH, Arver S, Behre HM, Buvat J, Meuleman E, Moncada I, Morales AM, Volterrani M, Yellowlees A, Howell JD, Channer KSTIMES2 Investigators Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 Study). Diabetes Care. 2011; 34:828-837|||Kapoor D, Goodwin E, Channer KS, Jones TH. Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol. 2006; 154:899-906|||Heufelder AE, Saad F, Bunck MC, Gooren L. Fifty‐two‐week treatment with diet and exercise plus transdermal testosterone reverses the metabolic syndrome and improves glycemic control in men with newly diagnosed type 2 diabetes and subnormal plasma testosterone. J Androl. 2009; 30:726-733|||Kalinchenko SY, Tishova YA, Mskhalaya GJ, Gooren LJG, Giltay EJ, Saad F. Effects of testosterone supplementation on markers of the metabolic syndrome and inflammation in hypogonadal men with the metabolic syndrome: the double‐blinded placebo‐controlled Moscow study. Clin Endocrinol. 2010; 73:602-612|||Malkin CJ, Jones TH, Channer KS. The effect of testosterone on insulin sensitivity in men with heart failure. Eur J Heart Fail. 2007; 9:44-50|||Corona G, Mannucci E, Forti G, Maggi M. Following the common association between testosterone deficiency and diabetes mellitus, can testosterone be regarded as a new therapy for diabetes? Int J Androl. 2009; 32:431-441|||Filippi S, Vignozzi L, Morelli A, Chavalmane AK, Sarchielli E, Fibbi B. Testosterone partially ameliorates metabolic profile and erectile responsiveness to PDE5 inhibitors in an animal model of male metabolic syndrome. J Sex Med. 2009; 6:3274-3288|||Gupta V, Bhasin S, Guo W, Singh R, Miki R, Chauhan P. Effects of dihydrotestosterone on differentiation and proliferation of human mesenchymal stem cells and preadipocytes. Mol Cell Endocrinol. 2008; 296:32-40|||Lin HY, Xu Q, Yeh S, Wang RS, Sparks JD, Chang C. Insulin and leptin resistance with hyperleptinemia in mice lacking androgen receptor. Diabetes. 2005; 54:1717-1725|||Ballester J, Munoz MC, Dominguez J, Rigau T, Guinovart JJ, Rodriguez‐Gil JE. Insulin‐dependent diabetes affects testicular function by FSH‐ and LH‐linked mechanisms. J Androl. 2004; 25:706-719|||Dhindsa S, Prabhakar S, Sethi M, Bandyopadhyay A, Chaudhuri A, Dandona P. Frequent occurence of hypogonadotropic hypogonadism in type 2 diabetes. J Clin Endocrinol Metab. 2004; 89:5462-5468|||Bruning JC, Gautam D, Burks DJ, Gillette J, Schubert M, Orban PC, Klein R, Krone W, Muller‐Wieland D, Kahn CR. Role of brain insulin receptor in control of body weight and reproduction. Science. 2000; 289:2122-2125|||Godsland IF, Wynn V, Crook D, Miller NE. Sex, plasma lipoproteins, and atherosclerosis: prevailing assumptions and outstanding questions. Am Heart J. 1987; 114:1467-1503|||Nettleship JE, Jones RD, Channer KS, Jones TH. Testosterone and coronary artery disease. Front Horm Res. 2009; 37:91-107|||Roger VL, Go AS, Lloyd‐Jones DM, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Soliman EZ, Sorlie PD, Sotoodehnia N, Turan TN, Virani SS, Wong ND, Woo D, Turner MB. Heart disease and stroke statistics—2012 update: a report from the American Heart Association. Circulation. 2012; 125:e2-e220|||Haffner SM, Mykkanen L, Valdez RA, Katz MS. Relationship of sex hormones to lipids and lipoproteins in nondiabetic men. J Clin Endocrinol Metab. 1993; 77:1610-1615|||Van Pottelbergh I, Braeckman L, Bacquer DD, De Backer G, Kaufman JM. Differential contribution of testosterone and estradiol in the determination of cholesterol and lipoprotein profile in healthy middle‐aged men. Atherosclerosis. 2003; 166:95-102|||Wranicz JK, Cyganjiewwicz I, Rosiak M, Kula P, Kula K, Zareba W. The relationship between sex hormones and lipid profile in men with coronary artery disease. Int J Cardiol. 2005; 101:105-110|||Agledahl I, Skjaerpe PA, Hansen JB, Svartberg J. Low serum testosterone in men is inversely associated with non‐fasting serum triglycerides: the Tromso Study. Nutr Metab Cardiovasc Dis. 2008; 18:256-262|||Vaidya D, Dobs A, Gapstur SM, Golden SH, Hankinson A, Liu K, Ouyang P. The association of endogenous sex hormones with lipoprotein subfraction profile in the multi‐ethnic study of atherosclerosis. Metabolism. 2008; 57:782-790|||Whitsel EA, Boyko EJ, Matsumoto AM, Anawalt BD, Siscovick DS. Intramuscular testosterone esters and plasma lipids in hypogonadal men: a meta‐analysis. Am J Med. 2001; 111:261-269|||Isidori AM, Giannetta E, Greco EA, Gianfrilli D, Bonifacio V, Isidori A, Lenzi A, Fabbri A. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle‐aged men: a meta‐analysis. Clin Endocrinol. 2005; 63:280-293|||Ridker PM, Cushman M, Stempfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1999; 336:973-979|||Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1999; 340:115-126|||Laaksonen DE, Niskanen L, Punnonen K, Nyyssonen K, Tuomainen TP, Salonen R, Rauramaa R, Salonen JT. Sex hormones, inflammation and the metabolic syndrome: a population‐based study. Eur J Endocrinol. 2003; 149:601-608|||Kapoor D, Clarke S, Stanworth R, Channer KS, Jones TH. The effect of testosterone replacement therapy on adipocytokines and C‐reactive protein in hypogonadal men with type 2 diabetes. Eur J Endocrinol. 2007; 156:595-602|||Kupelian V, Chiu GR, Araujo AB, Williams RE, Clark RV, McKinley JB. Association of sex hormones and C‐reactive protein levels in men. Clin Endocrinol. 2010; 72:527-533|||Zhang Y, Gao Y, Tan A, Yang X, Zhang H, Zhang S, Wu C, Lu Z, Wang M, Liao M, Qin X, Li L, Hu Y, Mo Z. Endogenous sex hormones and C‐reactive protein in healthy Chinese men. Clin Endocrinol. 2013; 78:60-66|||Bhatia V, Chauhuri A, Tomar R, Dhindsa S, Ghanim H, Dandona P. Low testosterone and high C‐reactive protein concentrations predict low hematocrit in type 2 diabetics. Diabetes Care. 2006; 29:2289-2294|||Maggio M, Basaria S, Ble A, Lauretani F, Bandinelli S, Ceda GP, Valenti G, Ling SM, Ferrucci L. Correlation between testosterone and inflammatory marker soluble interleukin‐6 receptor in older men. J Clin Endocrinol Metab. 2006; 91:345-347|||Nakhai Pour HR, Grobbee DE, Muller M, van der Schouw YT. Association of endogenous sex hormone with C‐reactive protein levels in middle‐aged and elderly men. Clin Endocrinol. 2007; 66:394-398|||Haring R, Baumeister SE, Volzke H, Dorr M, Kocher T, Nauck M, Wallaschofski H. Prospective inverse association of sex hormone concentrations in men with biomarkers of inflammation and oxidative stress. J Androl. 2012; 33:944-950|||Guler N, Batyraliev T, Dulger H, Ozkara C, Tuncer M, Aslan S, Okut H, Agirbasli M. The effects of short term (3 weeks) testosterone treatment on serum inflammatory markers in men undergoing coronary artery stenting. Int J Cardiol. 2006; 109:339-343|||Aversa A, Bruzziches R, Francomano D, Rosano G, Isidori AM, Lenzi A, Spera G. Effects of testosterone undecanoate on cardiovascular risk factors and atherosclerosis in middle‐aged men with late‐onset hypogonadism and metabolic syndrome: results from a 24‐month, randomized, double‐blind, placebo‐controlled study. J Sex Med. 2010; 7:3495-3503|||Singh AB, Hsia S, Alaupovic P, Sinha‐Hakim I, Woodhouse L, Buchanan TA, Shen R, Bross R, Berman N, Bhasin S. The effects of varying doses of T on insulin sensitivity, plasma lipids, apolipoproteins, and C‐reactive protein in healthy young men. J Clin Endocrinol Metab. 2002; 87:136-143|||Ng MKC, Liu PY, Williams AJ, Nakhla S, Ly LP, Handelsman DJ, Celermajer DS. Prospective study of effect of androgens on serum inflammatory markers in men. Arterioscler Thromb Vasc Biol. 2002; 22:1136-1141|||Nakhai Pour HR, Grobbee DE, Emmelot‐Vonk MH, Bots ML, Verhaar HJJ, van der Schouw YT. Oral testosterone supplementation and chronic low‐grade inflammation in elderly men: a 26‐week randomized, placebo‐controlled trial. Am Heart J. 2007; 154:1228.e1-1228.e7|||Malkin CJ, Pugh PJ, Jones RD, Kapoor D, Channer KS, Jones TH. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profile in hypogonadal men. J Clin Endocrinol Metab. 2004; 89:3313-3318|||Morita H, Wu J, Zipes DP. The QT syndromes: long and short. Lancet. 2008; 372:750-763|||Moss AJ, Schwartz PJ, Crampton RS, Tzivoni D, Locati EH, MacCluer J, Hall WJ, Weitkamp L, Vincent GM, Garson A., Jr The long QT syndrome: prospective longitudinal study of 328 families. Circulation. 1991; 84:1136-1144|||Hashiba K. Sex differences in phenotypic manifestation and gene transmission in the Romano‐Ward syndrome. Ann N Y Acad Sci. 1992; 644:142-156|||Lehman MH, Timothy KW, Frankovich D, Fromm BS, Keating M, Locati EH, Taggart RT, Towbin JA, Moss AJ, Schwartz PJ, Vincent GM. Age‐gender influence on the rate‐corrected QT interval and the QT‐heart rate relation in families with genotypically long QT syndrome. J Am Coll Cardiol. 1997; 29:93-99|||Makkar RR, Fromm BS, Steinman RT, Meissner MD, Lehmann MH. Female gender as a risk for Torsades de Pointes associated with cardiovascular drugs. JAMA. 1993; 270:2590-2597|||Merry M, Benzoin J, Alberta M, Moss AJ. Electrocardiographic quantification of ventricular repolarization. Circulation. 1989; 80:1301-1308|||Rautaharju PM, Zou SH, Wong S, Calhoun HP, Berens GS, Primes R, Avignon A. Sex differences in the evolution of the electrocardiographic QT interval with age. Can J Cardiol. 1992; 8:690-695|||Stamba‐Badiale M, Spagnolo D, Bosi G, Schwartz PJ. Are gender differences in QTc present at birth? MISNES investigators: multicenter Italian study on neonatal electrophysiology and sudden infant death syndrome. Am J Cardiol. 1995; 75:1277-1278|||Bidoggia H, Maciel JP, Capalozza N, Mosca S, Blaksley EJ, Valverde E, Bertran G, Arini P, Biagetti MO, Quinteiro RA. Sex differences on the electrocardiographic pattern of cardiac repolarization: possible role of testosterone. Am Heart J. 2000; 140:678-683|||Charbit B, Christin‐Maitre S, Demolis JL, Soustre E, Young J, Funck‐Brentano C. Effects of testosterone on ventricular repolarization in hypogonadic men. Am J Cardiol. 2009; 103:887-890|||van Noord C, Dorr M, Sturkenboom MC, Straus SM, Reffelmann T, Felix SB, Hofman A, Kors JA, Haring R, de Jong FH, Nauck M, Uitterlinden AG, Wallaschofski H, Witteman JC, Volzke H, Stricker BH. The association of serum testosterone levels and ventricular repolarization. Eur J Epidemiol. 2010; 25:21-28|||Pecori Giraldi F, Toja PM, Filippini B, Nichailidis J, Scacchi M, Tramba Badiale M, Cavagnini F. Increased prevalence of prolonged QT interval in males with primary or secondary hypogonadism: a pilot study. Int J Androl. 2010; 22:e132-e138|||Pecori Giraldi F, Manzoni G, Michailidis J, Scacchi M, Stramba‐Badiale M, Cavagnini F. High prevalence of prolonged QT interval in obese hypogonadal males. Obesity. 2011; 19:2015-2018|||Pecori Giraldi F, Toja PM, Michailidis G, Metinidou A, De Martin M, Scacchi M, Stramba‐Badiale M, Cavagnini F. High prevalence of prolonged QT duration in male patients with Cushing's disease. Exp Clin Endocrinol Diabetes. 2011; 119:221-224|||Bai CX, Kurokawa J, Tamagawa M, Nakaya H, Furukawa T. Nontranscriptional regulation of cardiac repolarization currents by testosterone. Circulation. 2005; 112:1701-1710|||Crouse JR, III, Craven TE, Hagaman AP, Bond MG. Association of coronary disease with segment specific intimal‐medial thickening of the extracranial carotid artery. Circulation. 1995; 92:1141-1147|||Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R. Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging. Circulation. 1986; 74:1399-1406|||Salonen JT, Salonen R. Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arterioscler Thromb Vasc Biol. 1991; 11:1245-1249|||Hodis HN, Mack WJ, LaBree L, Selzer RH, Liu C‐R, Liu C‐H, Azen SP. The role of carotid arterial intima‐media thickness in predicting clinical coronary events. Ann Intern Med. 1998; 128:262-269|||O'Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK., Jr Carotid‐artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. N Engl J Med. 1999; 340:14-22|||van den Beld AW, Bots ML, Janssen JAMLL, Pols HAP, Lamberts SWJ, Grobbee DE. Endogenous hormones and carotid atherosclerosis in elderly men. Am J Epidemiol. 2003; 157:25-31|||Fukui M, Kitagawa Y, Nakamura N, Kadono M, Mogami S, Hirata C, Ichio N, Wada K, Hasegawa G, Yoshikawa T. Association between serum testosterone concentration and carotid atherosclerosis in men with type 2 diabetes. Diabetes Care. 2003; 26:1869-1873|||De Pergola G, Pannacciulli N, Ciccone M, Tartagni M, Rizzon P, Giorgino R. Free testosterone plasma levels are negatively associated with the intima‐media thickness of the common carotid artery in overweight and obese glucose‐tolerant young adult men. Int J Obes Relat Metab Disord. 2003; 27:803-807|||Svartberg J, Von Muhlen D, Mathiesen E, Joakimsen O, Bonaa KH, Stensland‐Bugge E. Low testosterone levels are associated with carotid atherosclerosis in men. J Intern Med. 2006; 259:576-582|||Fu L, Gao QP, Shen JX. Relationship between testosterone and indexes indicating endothelial function in male coronary heart disease patients. Asian J Androl. 2008; 10:214-218|||Vikan T, Johnsen SH, Schirmer H, Njolstad I, Svartberg J. Endogenous testosterone and the prospective association with carotid atherosclerosis in men: the Tromso study. Eur J Epidemiol. 2009; 24:289-295|||Muller M, van den Beld AW, Bots ML, Grobbee DE, Lamberts SWJ, van der Schouw YT. Endogenous sex hormones and progression of carotid atherosclerosis in elderly men. Circulation. 2004; 109:2074-2079|||Hak AE, Witteman JCM, De Jong FH, Geerkings MI, Hofman A, Pols HAP. Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam Study. J Clin Endocrinol Metab. 2002; 87:3623-3639|||Demirbag R, Yilmaz R, Ulucay A, Unlu D. The inverse relationship between thoracic aortic intima media thickness and testosterone level. Endocr Res. 2005; 31:335-344|||Anker SD, Clark AL, Kemp M, Salsbury C, Teixeira MM, Hellewell PG, Coats AJ. Tumor necrosis factor and steroid metabolism in chronic heart failure: possible relation to muscle wasting. J Am Coll Cardiol. 1997; 30:997-1001|||Anker SD, Chua TP, Ponikowski P, Harrington D, Swan JW, Kox WJ, Poole‐Wilson PA, Coats AJ. Hormonal changes and catabolic/anabolic imbalance in chronic heart failure and their importance for cardiac cachexia. Circulation. 1997; 96:526-534|||Jankowska EA, Biel B, Majda J, Szklarska A, Lopuszanska M, Medras M, Anker SD, Banasiak W, Poole‐Wilson PA, Ponikowski P. Anabolic deficiency in men with chronic heart failure: prevalence and detrimental impact on survival. Circulation. 2006; 114:1829-1837|||Wehr E, Pilz S, Boehm BO, Marz W, Grammer T, Obermayer‐Pietsch B. Low free testosterone is associated with heart failure mortality in older men referred for coronary angiography. Eur J Heart Fail. 2011; 13:482-488|||Jankowska EA, Filippatos G, Ponikowska B, Borodulin‐Nadzieja L, Anker SD, Banasiak W, Polle‐Wilson PA, Ponikowski P. Reduction in circulating testosterone relates to exercise capacity in men with chronic heart failure. J Cardiac Fail. 2009; 15:442-450|||Caminiti G, Volterrani M, Iellamo F, Marazzi G, Massaro R, Miceli M, Mammi C, Piepoli M, Fini M, Rosano GM. Effect of long‐acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure: a double‐blind, placebo‐controlled, randomized study. J Am Coll Cardiol. 2009; 54:919-927|||Malkin CJ, Pugh PJ, West JN, van Beek EJ, Jones TH, Channer KS. Testosterone therapy in men with moderate severity heart failure: a double‐blind placebo controlled trial. Eur Heart J. 2006; 27:57-64|||Pugh PJ, Jones RD, West JN, Jones TH, Channer KS. Testosterone treatment for men with chronic heart failure. Heart. 2004; 90:446-447|||Iellamo F, Volterrani M, Caminiti G, Karam R, Massaro R, Fini M, Collins P, Rosano GM. Testosterone therapy in women with chronic heart failure: a pilot double‐blind, randomized, placebo‐controlled study. J Am Coll Cardiol. 2010; 56:1310-1316|||Toma M, McAlister FA, Coglianese EE, Vidi V, Vasaiwala S, Bakal JA, Armstrong PW, Ezekowitz JA. Testosterone supplementation in heart failure: a meta‐analysis. Circ Heart Fail. 2012; 5:315-321|||Czesla M, Mehlhorn G, Fritzsche D, Asmussen G. Cardiomyoplasty—improvement of muscle fiber type transformation by an anabolic steroid (metenolone). J Mol Cell Cardiol. 1997; 29:2989-2996|||Calof OM, Singh AB, Lee ML, Kenny AM, Urban RJ, Tenover JL, Bhasin S. Adverse events associated with testosterone replacement in middle‐aged and older men: a meta‐analysis of randomized, placebo‐controlled trials. J Gerontol. 2005; 60:1451-1457|||Fernandez‐Balsells MM, Murad MH, Lane M, Lampropulos JF, Albuquerque F, Mullan RJ, Agrwal N, Elamin MB, Gallegos‐Orozco JF, Wang AT, Erwin PJ, Bhasin S, Montori VM. Adverse effects of testosterone therapy in adult men: a systemic review and meta‐analysis. J Clin Endocrinol Metab. 2010; 95:2560-2575|||Shores MM, Smith NL, Forsberg CW, Anawalt BD, Matsumoto AM. Testosterone treatment and mortality in men with low testosterone levels. J Clin Endocrinol Metab. 2012; 97:2050-2058|||Glueck CJ, Richardson‐Royer C, Schultz R, Burger T, Bowe D, Padda J, Wang P. Testosterone therapy, thrombophilia‐hypofibrinolysis, and hospitalization for deep venous thrombosis‐pulmonary embolus: an exploratory, hypothesis‐generating study. Clin Appl Thromb Hemost. 2013. 10.1177/1076029613499819|||Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ulloor J, Zhang A, Choong K, Lakshman KM, Mazer NA, Miciek R, Krasnoff J, Elmi A, Knapp PE, Brooks B, Appleman E, Aggarwal S, Bhasin G, Hede‐Brierley L, Bhatia A, Collins L, LeBrasseur N, Fiore LD, Bhasin S. Adverse events associated with testosterone administration. N Engl J Med. 2010; 363:109-122|||Vigen R, O'Donnell CI, Baron AE, Grunwald GK, Maddox TM, Bradley SM, Barqawi A, Woning G, Wierman ME, Plomondon ME, Rumsfeld JS, Ho M. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013; 310:1829-1836|||Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM. Testosterone therapy in adult men with androgen deficiency syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2006; 91:1995-2010