Testosterone replacement therapy and cardiovascular risk factors modification

Aging Male

Volumn 14, Issue 2, 2011, Pages 83-90

  Chahla, Elie J ^a,b   El Hayek, Mireille ^a,b   Morley, John E ^a,b  

^a VETERANS AFFAIRS MEDICAL CENTER   (United States)

^b SAINT LOUIS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

cardiovascular risk factors; heart failure; Hypogonadism; testosterone replacement therapy

Indexed keywords

ANDROSTANOLONE; HEMOGLOBIN A1C; LACTATE DEHYDROGENASE; PLACEBO; TESTOSTERONE; TESTOSTERONE CIPIONATE; TUMOR NECROSIS FACTOR ALPHA;

ANDROGEN DEFICIENCY; ANDROGEN THERAPY; ANGINA PECTORIS; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CONGESTIVE HEART FAILURE; CORONARY ARTERY DISEASE; DEATH; DRUG MECHANISM; EDEMA; FRAIL ELDERLY; HEART ARRHYTHMIA; HEART FAILURE; HEART INFARCTION; HEART PROTECTION; HUMAN; HYPOGONADISM; NONHUMAN; PRIORITY JOURNAL; REVIEW; RISK MANAGEMENT; SIDE EFFECT; WATER RETENTION;

AGED; AGED, 80 AND OVER; ANIMALS; CARDIOVASCULAR DISEASES; FRAIL ELDERLY; HORMONE REPLACEMENT THERAPY; HUMANS; MALE; RISK FACTORS; TESTOSTERONE;

EID: 79955692873     PISSN: 13685538     EISSN: 14730790     Source Type: Journal    
DOI: 10.3109/13685538.2010.541538     Document Type: Review

References (91)

1. Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Baltimore longitudinal study of aging. Longitudinal effects of aging on serumtotal and free testosterone levels in healthy men. J Clin Endocrinol Metab 2001;86:724-773.
2. Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, Bemner 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. (Pubitemid 34158223)
3. Liu PY, Beilin J, Meier C, Nguyen TV, Center JR, Leedman PJ, Seibel MJ, Eisman JA, Handelsman DJ. Age-related changes in serum testosterone and sex hormone binding globulin in Australian men: longitudinal analyses of two geographically separate regional cohorts. J Clin Endocrinol Metab 2007;92:3599-3603. (Pubitemid 47435341)
4. Morley JE, Kaiser FE, Perry HM 3rd, Patrick P, Morley PM, Stauber PM, Vellas B, Baumgartner RN. Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in health older men. Metabolism 1997;46:410-413. (Pubitemid 27172090)
5. Nolten WE. Androgen deficiency in the aging male: when to evaluate and when to treat. Curr Urol Rep. 2000;1:313-319.
6. Morley JE. Androgens and aging. Maturitas 2001;38:61-71.
7. Dominguez LJ, Barbagallo M, Morley J. The paradigm of life extension. J Am Med Dir Assoc 2010;11:457-458.
8. Bain J. Department of Medicine, University of Toronto, Division of Endocrinology and Metabolism, Mount Sinai Hospital, Toronto, Ontario, Canada. Testosterone and the aging male: to treat or not to treat? Maturitas. 2010;66:16-22. Epub 2010 Feb 13.
9. Abellan van Kan G, Rolland YM, Morley JE, Vellas B. Frailty: toward a clinical definition. J Am Med Dir Assoc 2008;9:71-72. (Pubitemid 351189169)
10. Morley JE. Anorexia, sarcopenia, and aging. Nutrition 2001;17: 660-663. (Pubitemid 32640158)
11. Chu LW, Tam S, Wong RL, et al. Bioavailable testosterone predicts a lower risk of Alzheimer's disease in older men. J Alzheimers Dis 2010;21:1335-1345.
12. Morley JE. Anorexia, weight loss, and frailty. J Am Med Dir Assoc 2010;11:225-228.
13. Morley JE. Anabolic steroids and frailty. J Am Med Dir Assoc 2010;11:533-536.
14. Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, DeSimone G, Ferguson TB, Ford E, Furie K, Gillespie, et al., American Heart Association Statistics Committee and Stroke Statistics. Executive summary: heart disease and stroke statistics - 2010; Update: a report from the American Heart Association. Circulation 2010;121:948-954.
15. Turhan S, Tulunay C, Gulec S, Ozdol C, Kilickap M, Altin T, Gerede M, Erol C. The association between androgen levels and premature coronary artery disease in men. Coron Artery Dis 2007;18:159-162. (Pubitemid 46608491)
16. 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. (Pubitemid 350291241)
17. 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. Epub 2007 November 26. (Pubitemid 350291241)
18. Stanworth RD, Jones TH. Testosterone in obesity, metabolic syndrome and type 2 diabetes. Front Horm Res 2009;37:74-90 [review].
19. Cummings-Vaughn LA, Malmstrom TK, Morley JE, Miller DK. Testosterone is not associated with mortality in older African- American males. AgingMale 2010;August 4 [Epub ahead of print].
20. 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.
21. 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. Euro Heart J. 2000;890-894. (Pubitemid 30307417)
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 Epid 2003;157:25-31. (Pubitemid 36043733)
23. Güder G, Frantz S, Bauersachs J, Allolio B, Ertl G, Angermann CE, Stö rk S. Low circulating androgens and mortality risk in heart failure. Heart. 2010;96:504-509; Epub 2009 Oct 28.
24. Charbit B, Christin-Maître S, Démolis JL, Soustre E, Young J, Funck-Brentano C. Effects of testosterone on ventricular repolarization in hypogonadic men. Am J Cardiol 2009;103: 887-890. Epub 24 Jan 2009.
25. Wang C, Nieschlag E, Swerdloff RS, Behre H, Hellstrom WJ, Gooren LJ, Kaufman JM, Legros JJ, Lunenfield B, Morales A, et al. ISA, ISSAM, EAU, EAAS and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males. Aging Male 2009;12:5-12.
26. Traish AM, Abdou R, Kypreos KE. Androgen deficiency and atherosclerosis: the lipid link. Vascul Pharmacol 2009;51:303-313.
27. 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. (Pubitemid 43997730)
28. Hartgens F, Kuipers H. Effects of androgenic-anabolic steroids in athletes. Sports Med 2004;34:513-554. (Pubitemid 38981844)
29. Malkin CJ, Pugh PJ, Jones RD, Kapoor D, Channer KS, Jones TH. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab 2004;89:3313-3318. (Pubitemid 38951897)
30. Zumoff B, Strain GW,Miller LK, Rosner W, Senie R, Seres DS, Rosenfeld RS. Plasma free and non sex-hormone-bindingglobulin- bound testosterone are decreased in obese men in proportion to their degree of obesity. J Clin Endocrinol Metab 1990;71:929-931.
31. Pasquali R, Casimirri F, Cantobelli S, Melchionda N, Morselli Labate AM, Fabbri R, Capelli M, Bortoluzzi L. Effect of obesity and body fat distribution on sex hormones and insulin in men. Metabolism 1991;40:101-104.
32. Vitale C, Mendelsohn ME, Rosano GM. Gender differences in the cardiovascular effect of sex hormones. Nat Rev Cardiol 2009;6:532-542.
33. Zitzmann M. Testosterone deficiency, insulin resistance and the metabolic syndrome. Nat Rev Endocrinol 2009;5:673-681.
34. Kalyani RR, Dobs AS. Androgen deficiency, diabetes, and the metabolic syndrome in men. Curr Opin Endocrinol Diabetes Obes 2007;14:226-234. (Pubitemid 46684478)
35. Selvin E, Feinleib M, Zhang L, Rohrmann S, Rifaii N, Nelson WG, Dobs A, Basaria S, Golden SH, Platz EA. Androgens and diabetes in men: results from the Third National Health and Nutrition Examination Survey (NHANES III). Diabetes Care 2007;30:234-238. (Pubitemid 46198324)
36. Haffner SM, Valdez RA, Stern MP, Katz MS. Obesity, body fat distribution and sex hormones in men. Int J Obes 1993;17:634-639.
37. Phillips GB. Relationships in men of sex hormones, insulin, adiposity, and risk factors for myocardial infarction. Metabolism 2003;52:784-790. (Pubitemid 36896315)
38. Khaw KT, Barrett-Connor E. Blood pressure and endogenous testosterone in men: an inverse relationship. J Hypertens 1988;6: 329-332.
39. Fogari R, Preti P, Zoppi A, Fogari E, Rinaldi A, Corradi L, Mugellini A. Serum testosterone levels and arterial blood pressure in the elderly. Hypertens Res 2005;28:625-630. (Pubitemid 41601034)
40. Webb CM, Elkington AG, Kraidly MM, Keenan N, Pennell DJ, Collins P. 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. (Pubitemid 351625084)
41. Bernini G, Versari D, Moretti A, Virdis A, Ghiadoni L, Bardini M, Taurino C, Canale D, Taggei S, Salvetti A. Vascular reactivity in congenital hypogonadal men before and after testosterone replacement therapy. J Clin Endocrinol Metab 2006;91:1691-1697.
42. Yaron M, Greenman Y, Rosenfeld JB, Izhakov E, Limor R, Osher E, Shenkerman G, Tordjman K, Stern N. Effect of testosterone replacement therapy on arterial stiffness in older hypogonadal men. Eur J Endocrinol 2009;160:839-846.
43. Reckelhoff JF, Zhang H, Granger JP. Testosterone exacerbates hypertension and reduces pressure-natriuresis in male spontaneously hypertensive rats. Hypertension 1998;31:435-439.
44. Yanes LL, Sartori-Valinotti JC, Iliescu R, Romero DG, Racusen LC, Zhang H, Reckelhoff JE. Testosterone-dependent hypertension and upregulation of intrarenal angiotensinogen in Dahl salt-sensitive rats. Am J Physiol Renal Physiol 2009;296:F771-F779.
45. Vakil RJ. An evaluation of testosterone propionate therapy in cases of angina pectoris. Ind Med Gaz 1949;84:83-88.
46. Ganelina IE. On treatment of angina pectoris with testosterone [article in undetermined language]. Ter Arkh 1951;23:28-36.
47. Aubertin E. Testosterone propionate in the treatment of angina pectoris [article in undetermined language]. J Med Bord 1953;130:686-687.
48. Muderrisoglu B. The value of testosterone proprionate (perandrone) in the treatment of heart disease and angina pectoris [article in un-determined language]. Brux Med 1953;33:969-980.
49. Gmachl E, Hortnagl W. The treatment of angina pectoris with laevadenyl and testoviron [German]. Wien Klin Wochenschr 1954;66:593-595.
50. Wu SZ, Weng XZ. Therapeutic effects of an androgenic preparation on myocardial ischemia and cardiac function in 62 elderly male coronary heart disease patients. Chin Med J 1993;106:415-418.
51. Jaffe MD. Effect of testosterone cypionate on postexercise ST segment depression. Brit Heart J 1977;39:1217-1222. (Pubitemid 8206514)
52. English KM, Steeds RP, Jones TH, Diver MJ, Channer KS. Lowdose transdermal therapy improves angina threshold in men with chronic stable angina: a randomized, double-blind, placebocontrolled study. Circulation 2000;102:1906-1911.
53. Malkin CJ, Pugh PJ, Morris PD, Kerry KE, Jones RD, Jones TH, Channer KS. Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life. Heart 2004;90:871-876. (Pubitemid 39005930)
54. Paulusinski R, Barud W, Bilan A, Witczak A, Myslinski W, Hanzlik J. Effect of dihydrotestosterone treatment on exercise induced ischemia in men with stable ischemic heart disease [Polish] Pol Merkur Lekarski 2000;9:533-534.
55. Cornoldi A, Caminiti G, Marazzi G, Vitale C, Patrizi R, Volterrani M, Miceli M, Volterrani M, Miceli M, Fini M, Spera G, Rosano G. Effects of chronic testosterone administration on myocardial ischemia, lipid metabolism and insulin resistance in elderly male diabetic patients with coronary artery disease. Int J Cardiol 2010;142:50-55.
56. Mathur A, Malkin C, Saeed B, Muthusamy R, Jones TH, Channer K. Long-term benefits of testosterone replacement therapy on angina threshold and atheroma in men. Eur J Endocrinol 2009;161:443-449.
57. English KM, Jones RD, Jones TH, Morice AH, Channer KS. Testosterone acts as a coronary vasodilator by a calcium antagonistic action. J Endocrinol Invest 2002;25:455-458. (Pubitemid 34516593)
58. Scragg JL, Dallas ML, Peers C. Molecular Requirements for Ltype Ca2+channel blockade by testosterone. Cell Calcium 2007;42:11-15. (Pubitemid 46760450)
59. Heidenreich PA, Fonarow GC. Are registry hospitals different? A comparison of patients admitted to hospitals of a commercial heart failure registry with those from national and community cohorts. Am Heart J 2006;152:935-939. (Pubitemid 44632955)
60. Pascual-Figal DA, Tornel PL, Nicolás F, Sánchez-Más J, Martínez MD, Gracia MR, Garrido IP, Ruipérez JA, Valdés M. Sex hormone-binding globulin: a new marker of disease severity and prognosis in men with chronic heart failure. Rev Esp Cardiol. 2009;62:1381-1387.
61. Omran ML, Morley JE. Assessment of protein energy malnutrition in older persons, part I: history, examination, body composition, and screening tools. Nutrition 2000;16:50-63. (Pubitemid 30050726)
62. Omran ML, Morley JE. Assessment of protein energy malnutrition in older persons, Part II: laboratory evaluation. Nutrition 2000;16:131-140. (Pubitemid 30103716)
63. Güder G, Frantz S, Bauersachs J, Allolio B, Ertl G, Angermann CE, Stö rk S. Low circulating androgens and mortality risk in heart failure. Heart 2010;96:504-509; doi:10.1136/hrt.2009.181065.
64. 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.
65. Jankowska EA, Filippatos G, Ponikowska B, Borodulin-Nadzieja L, Anker SD, Banasiak W, Poole-Wilson PA, Ponikowski P. Reduction in circulating testosterone relates to exercise capacity in men with chronic heart failure. J Card Fail 2009;15:442-450; Epub 10 Feb 2009.
66. Somani B, Khan S, Donat R. Screening for metabolic syndrome and testosterone deficiency in patients with erectile dysfunction: results from the first UK prospective study. BJU Int 2010; 106:688-690.
67. Borst SE, Quindry JC, Yarrow JF, Conover CF, Powers SK. Testosterone administration induces protection against global myocardial ischemia. Horm Metab Res 2010;42:122-129; Epub 27 October 2009.
68. Li ZB, Wang J, Wang JX, Chen XM, Jiang SS. Testosterone therapy improves cardiac function of male rats with right heart failure. Zhonghua Nan Ke Xue 2009;15:994-1000.
69. Pan Y, Zhang H, Acharya AB, Patrick PH, Oliver D, Morley JE. Effect of testosterone on functional recovery in a castrate male rat stroke model. Brain Res 2005;1043:195-204. (Pubitemid 40603387)
70. Pecori Giraldi F, Toja PM, Filippini B, Michailidis J, Scacchi M, Stramba Badiale M, Cavagnini F. Increased prevalence of prolonged QT interval in males with primary or secondary hypogonadism: a pilot study. Int J Androl 2010;33:e132-e138; Epub 11 Sept 2009.
71. Charbit B, Christin-Maitre S, Demolis JL, Soustre E, Young J, Funck-Frentano C. Effects of testosterone on ventricular repolarization in hypogonadic men. Am J Cardiol 2009;103: 887-890.
72. Lai J, Zhou D, Xia S, Shang Y, Want L, Zheng L, Zhu J. Reduced testosterone levels in males with lone atrial fibrillation. Clin Cardiol 2009;32:43-46.
73. Liu T, Shehata M, Li G, Wang X. Androgens and atrial fibrillation: Friends or foes? Int J Cardiol 2010;145: 365-367.
74. Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ullor J, Zhang A, et al. Adverse events associated with testosterone administration. N Engl J Med 2010;363:109.
75. Omran ML, Morley JE. Assessment of protein energy malnutrition in older persons. Part II: laboratory evaluation. Nutrition 2000;16:131-140. (Pubitemid 30103716)
76. Ahmed A, Jones L, Hays CL. DEFEAT heart failure: assessment and management of heart failure in nursing homes made easy. J Am Med Dir Assoc 2008;9:383-389.
77. Morley JE. Developing novel therapeutic approaches to frailty. Curr Pharm Des 2009;15:3384-3395.
78. Gobbens RJ, van Assen MA, Luijkx KG, Wijnen-Sponselle MT, Schols JM. Determinants of frailty. J Am Med Dir Assoc 2010;11:356-364.
79. van Kan GA, Rolland Y, Bergman H, Abellan van Kan G, Rolland Y, Bergman H, Morley JE, Kritchevsky SB, Vellas B. The IANA task force on frailty assessment of older people in clinical practice. J Nutr Hlth Aging 2008;12:29-37. (Pubitemid 351156012)
80. 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 A Biol Sci Med Sci 2005;60:1451-1457. (Pubitemid 41798454)
81. 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. (Pubitemid 27509374)
82. Pugh PJ, Jones RD, West JN, Jones TH, Channer KS. Testosterone treatment for men with chronic heart failure. Heart 2010;90:446-447.
83. 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 randomized placebo controlled trail. Eur Heart J 2006;27:57-64. (Pubitemid 41785933)
84. Srinivas-Shankar U, Roberts SA, Connolly MJ, O'Connell MD, Adams JE, Oldham JA, Wu FC. Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 2010;95:639-650.
85. Kenny AM, Kleppinger A, Annis K, Rathier M, Browner B, Judge JO, McGee D. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels, low bone mass, and physical frailty. J Am Geriatr Soc 2010;58:1134-1143.
86. Chapman IM, Visvanathan R, Hammond AJ, Morley JE, Field JB, Tai K, Belobrajdic DP, Chen RY, Horowitz M. Effect of testosterone and a nutritional supplement, alone and in combination, on hospital admissions in undernourished older men and women. Am J Clin Nutr 2009;89:880-889.
87. Wang C, Nieschlag E, Swerdloff R, Behre HM, Hellstrom WJ, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morales A, et al. Investigation, treatment and monitoring of late-onset hypogonadism in males. Eur J Endocrinol 2008;159:507-514.
88. Morley JE, Haren MT, Rolland Y, Kim MJ. Frailty. Med Clin North Am 2006;90:837-847. (Pubitemid 44354823)
89. Morley JE. Should frailty be treated with testosterone? Aging Male 2011;14:1-3.
90. Morley JE, Argiles JM, Evans WJ, Bhasin S, Cella D, Deutz NE, Doehner W, Fearon KC, Ferrucci L, Hellerstein MK, et al. Nutritional recommendations for the management of sarcopenia. J Am Med Dir Assoc 2010;11:391-396.
91. 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 A Biol Sci Med Sci 2005;60:1451-1457. (Pubitemid 41798454)