, Volume 50, Issue 2, pp 320–325 | Cite as

Testosterone in men with hypogonadism and high cardiovascular risk, Pros

  • Giuseppe M. C. RosanoEmail author
  • Cristiana Vitale
  • Massimo Fini
Pros and Cons in Endocrine Practice


Although numerous randomized studies have shown that testosterone replacement therapy (TRT) improves intermediate outcomes in patients at risk and in those with proven cardiovascular disease (CVD), results derived mainly from registries and observational studies have suggested an increased cardiovascular risk in elderly men receiving often supra-therapeutic doses of testosterone. Recent meta-analyses have shown that when testosterone has been used in patients with pre-existing cardiovascular conditions, the effect on the disease has been either beneficial or neutral. Similar results have been reported in hypo- and eugonadal men. Contrasting results have been reported by two trials of testosterone treatment in frail elderly men. Reports from poorly analyzed databases have reported an increased risk of cardiovascular events with testosterone use. More recently, a population-based study showed no increased cardiovascular risk of testosterone replacement in hypogonadal men. Available data from controlled clinical trials suggest that the use of testosterone in elderly men does not increase cardiovascular risk nor the risk of events. Studies in men with CVD, angina, or heart failure report a benefit from testosterone replacement in men with or without hypogonadism. Therefore, at present, the cardiovascular benefits of TRT in elderly men outweigh the risks. This is particularly evident in those men with pre-existing CVD.


Testosterone Angina Heart failure Coronary artery disease Prognosis Myocardial infarction Frailty Elderly 


  1. 1.
    J.M. Kaufman, A. Vermeulen, The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr. Rev. 26, 833–876 (2005)CrossRefPubMedGoogle Scholar
  2. 2.
    C.C. Carson 3rd, G. Rosano, Exogenous testosterone, cardiovascular events, and cardiovascular risk factors in elderly men: a review of trial data. J. Sex Med. 9(1), 54–67 (2012)CrossRefPubMedGoogle Scholar
  3. 3.
    G.M. Rosano, A. Cornoldi, M. Fini, Effects of androgens on the cardiovascular system. J. Endocrinol. Invest. 28(3 Suppl), 32–38 (2005)PubMedGoogle Scholar
  4. 4.
    A.M. Traish, Adverse health effects of testosterone deficiency (TD) in men. Steroids 88, 106–116 (2014)CrossRefPubMedGoogle Scholar
  5. 5.
    R.D. Jones, J.E. Nettleship, D. Kapoor, H.T. Jones, K.S. Channer, Testosterone and atherosclerosis in aging men: purported association and clinical implications. Am. J. Cardiovasc. Drugs 5, 141–154 (2005)CrossRefPubMedGoogle Scholar
  6. 6.
    C.J. Malkin, P.J. Pugh, P.D. Morris, S. Asif, T.H. Jones, K.S. Channer, Low serum testosterone and increased mortality in men with coronary heart disease. Heart 96, 1821–1825 (2010)CrossRefPubMedGoogle Scholar
  7. 7.
    G.M. Rosano, I. Sheiban, R. Massaro, P. Pagnotta, G. Marazzi, C. Vitale, G. Mercuro, M. Volterrani, A. Aversa, M. Fini, Low testosterone levels are associated with coronary artery disease in male patients with angina. Int. J. Impot. Res. 19, 176–182 (2007)CrossRefPubMedGoogle Scholar
  8. 8.
    K.M. English, O. Mandour, R.P. Steeds, M.J. Diver, T.H. Jones, K.S. Channer, Men with coronary artery disease have lower levels of androgens than men with normal coronary angiograms. Eur. Heart J. 21, 890–894 (2000)CrossRefPubMedGoogle Scholar
  9. 9.
    F.R. Sattler, C. Castaneda-Sceppa, E.F. Binder, E.T. Schroeder, Y. Wang, S. Bhasin, M. Kawakubo, Y. Stewart, K.E. Yarasheski, J. Ulloor, P. Colletti, R. Roubenoff, S.P. Azen, Testosterone and growth hormone improve body composition and muscle performance in older men. J. Clin. Endocrinol. Metab. 94, 1991–2001 (2009)PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    U. Srinivas-Shankar, S.A. Roberts, M.J. Connolly, M.D. O’Connell, J.E. Adams, J.A. Oldham, F.C. Wu, 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. 95, 639–650 (2010)CrossRefPubMedGoogle Scholar
  11. 11.
    C. Ohlsson, E. Barrett-Connor, S. Bhasin et al., 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. Cardiol. 58(16), 1674–1681 (2011)CrossRefPubMedGoogle Scholar
  12. 12.
    C. Vitale, M.E. Mendelsohn, G.M. Rosano, Gender differences in the cardiovascular effect of sex hormones. Nat. Rev. Cardiol. 6, 532–542 (2009)CrossRefPubMedGoogle Scholar
  13. 13.
    T.H. Jones, Testosterone deficiency: a risk factor for cardiovascular disease? Trends Endocrinol. Metab. 21, 496–503 (2010)CrossRefPubMedGoogle Scholar
  14. 14.
    T.H. Jones, F. Saad, The effects of testosterone on risk factors for, and the mediators of, the atherosclerotic process. Atherosclerosis 207, 318–327 (2009)CrossRefPubMedGoogle Scholar
  15. 15.
    A. Aversa, R. Bruzziches, D. Francomano et al., 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. 7(10), 3495–3503 (2010)CrossRefPubMedGoogle Scholar
  16. 16.
    E.A. Jankowska, B. Biel, J. Majda et al., Anabolic deficiency in men with chronic heart failure: prevalence and detrimental impact on survival. Circulation 114, 1829–1837 (2006)CrossRefPubMedGoogle Scholar
  17. 17.
    G.M. Rosano, Androgens and coronary artery disease. A sex-specific effect of sex hormones? Eur. Heart J. 21(11), 868–871 (2000)CrossRefPubMedGoogle Scholar
  18. 18.
    G. Corona, E. Maseroli, G. Rastrelli et al., Cardiovascular risk associated with testosterone-boosting medications: a systematic review and meta-analysis. Expert Opin. Drug Saf. 13(10), 1327–1351 (2014)CrossRefPubMedGoogle Scholar
  19. 19.
    L. Xu, G. Freeman, B.J. Cowling, M.C. Schooling, Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials. BMC Med. 11, 108 (2013)PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    O.M. Calof, A.B. Singh, M.L. Lee et al., 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. 60, 1451–1457 (2005)CrossRefPubMedGoogle Scholar
  21. 21.
    R.M. Haddad, C.C. Kennedy, S.M. Caples et al., Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clin. Proc. 82, 29–39 (2007)CrossRefPubMedGoogle Scholar
  22. 22.
    M.M. Fernandez-Balsells, M.H. Murad et al., Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 95, 2560–2575 (2010)CrossRefPubMedGoogle Scholar
  23. 23.
    D. Kapoor, E. Goodwin, K.S. Channer, T.H. Jones, Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur. J. Endocrinol. 154, 899–906 (2006)CrossRefPubMedGoogle Scholar
  24. 24.
    D. Kapoor, S. Clarke, R. Stanworth, K.S. Channer, T.H. Jones, The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes. Eur. J. Endocrinol. 156, 595–602 (2007)CrossRefPubMedGoogle Scholar
  25. 25.
    A.E. Heufelder, F. Saad, M.C. Bunck, L. Gooren, 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. Andol. 30, 726–733 (2009)CrossRefGoogle Scholar
  26. 26.
    S.Y. Kalinchenko, Y.A. Tishova, G.J. Mskhalaya, L.J. Gooren, E.J. Giltay, F. Saad, Effects of testosterone supplementation on markers of the metabolic syndrome and inflammation in hypogonadal men with the metabolic syndrome: the double-blind placebo-controlled Moscow study. Clin. Endocrinol. (Oxf) 73, 602–612 (2010)CrossRefGoogle Scholar
  27. 27.
    A. Mathur, C. Malkin, B. Saeed, R. Muthusamy, T.H. Jones, K. Channer, Long-term benefits of testosterone replacement therapy on angina threshold and atheroma in men. Eur. J. Endocrinol. 161(3), 443–449 (2009)CrossRefPubMedGoogle Scholar
  28. 28.
    G. Corona, G. Rastrelli, E. Maseroli et al., Low testosterone syndrome protects subjects with high cardiovascular risk burden from major adverse cardiovascular events. Andrology 2(5), 741–747 (2014)CrossRefPubMedGoogle Scholar
  29. 29.
    C.J. Malkin, P.J. Pugh, P.D. Morris et al., Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life. Heart 90, 871–876 (2004)PubMedCentralCrossRefPubMedGoogle Scholar
  30. 30.
    C.J. Malkin, P.J. Pugh, R.D. Jones, D. Kapoor, K.S. Channer, T.H. Jones, The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J. Clin. Endocrinol. Metab. 89, 3313–3318 (2004)CrossRefPubMedGoogle Scholar
  31. 31.
    A.M. Smith, K.M. English, C.J. Malkin, R.D. Jones, T.H. Jones, K.S. Channer, Testosterone does not adversely affect fibrinogen or tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) levels in 46 men with chronic stable angina. Eur. J. Endocrinol. 152, 285–291 (2005)CrossRefPubMedGoogle Scholar
  32. 32.
    M. Yaron, Y. Greenman, J.B. Rosenfeld et al., Effect of testosterone replacement therapy on arterial stiffness in older hypogonadal men. Eur. J. Endocrinol. 160(5), 839–846 (2009)CrossRefPubMedGoogle Scholar
  33. 33.
    A. Cornoldi, G. Caminiti, G. Marazzi et al., 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. 142, 50–55 (2010)CrossRefPubMedGoogle Scholar
  34. 34.
    K.M. English, R.P. Steeds, T.H. Jones, M.J. Diver, K.S. Channer, Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: a randomized, double-blind, placebo-controlled study. Circulation 102, 1906–1911 (2000)CrossRefPubMedGoogle Scholar
  35. 35.
    G.M. Rosano, F. Leonardo, P. Pagnotta et al., Acute anti-ischemic effect of testosterone in men with coronary artery disease. Circulation 99(13), 1666–1670 (1999)CrossRefPubMedGoogle Scholar
  36. 36.
    M. Volterrani, G. Rosano, F. Iellamo, Testosterone and heart failure. Endocrine 42(2), 272–277 (2012)CrossRefPubMedGoogle Scholar
  37. 37.
    J.B. Schwartz, M. Volterrani, G. Caminiti et al., Effects of testosterone on the Q-T interval in older men and older women with chronic heart failure. Int. J. Androl. 34(5 Pt 2), e415–e421 (2011)CrossRefPubMedGoogle Scholar
  38. 38.
    F. Iellamo, M. Volterrani, G. Caminiti et al., Testosterone therapy in women with chronic heart failure: a pilot double-blind, randomized, placebo-controlled study. J. Am. Coll. Cardiol. 56(16), 1310–1316 (2010)CrossRefPubMedGoogle Scholar
  39. 39.
    F. Iellamo, G. Rosano, M. Volterrani, Testosterone deficiency and exercise intolerance in heart failure: treatment implications. Curr. Heart Fail Rep. 7(2), 59–65 (2010)CrossRefPubMedGoogle Scholar
  40. 40.
    G. Caminiti, M. Volterrani, F. Iellamo et al., 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. 54(10), 919–927 (2009)CrossRefPubMedGoogle Scholar
  41. 41.
    P.J. Pugh, R.D. Jones, J.N. West, T.H. Jones, K.S. Channer, Testosterone treatment for men with chronic heart failure. Heart 90, 446–447 (2004)PubMedCentralCrossRefPubMedGoogle Scholar
  42. 42.
    P.J. Pugh, R.D. Jones, C.J. Malkin et al., Physiologic testosterone therapy has no effect on serum levels of tumour necrosis factor-alpha in men with chronic heart failure. Endocr. Res. 31, 271–283 (2005)CrossRefPubMedGoogle Scholar
  43. 43.
    C.J. Malkin, P.J. Pugh, J.N. West, E.J. van Beek, T.H. Jones, K.S. Channer, Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial. Eur. Heart J. 27, 57–64 (2006)CrossRefPubMedGoogle Scholar
  44. 44.
    M. Toma, F.A. McAlister, E.E. Coglianese et al., Testosterone supplementation in heart failure: a meta-analysis. Circ. Heart Fail 5(3), 315–321 (2012)CrossRefPubMedGoogle Scholar
  45. 45.
    S. Basaria, A.D. Coviello, T.G. Travison et al., Adverse events associated with testosterone administration. N. Engl. J. Med. 363, 109–122 (2010)PubMedCentralCrossRefPubMedGoogle Scholar
  46. 46.
    R. Vigen, C.I. O’Donnell, A.E. Baron et al., Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA 310(17), 1829–1836 (2013)CrossRefPubMedGoogle Scholar
  47. 47.
    A. Aversa, D. Francomanno, A. Lenzi, Is testosterone treatment dangerous for the cardiovascular system in older hypogonadal men? IJC Metab. Endocr 4, 1–3 (2014). doi: 10.1016/j.ijcme.2014.08.001 CrossRefGoogle Scholar
  48. 48.
    A. Morgentaler, B. Lunenfeld, Testosterone and cardiovascular risk: world’s experts take unprecedented action to correct misinformation. Aging Male 17(2), 63–65 (2014)CrossRefPubMedGoogle Scholar
  49. 49.
    W.D. Finkle, S. Greenland, G.K. Ridgeway et al., Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One 9(1), e85805 (2014)PubMedCentralCrossRefPubMedGoogle Scholar
  50. 50.
    J. Baillargeon, R.J. Urban, Y.-F. Kuo et al., Risk of myocardial infarction in older men receiving testosterone therapy. Ann. Pharmacother. 48(9), 1138–1144 (2014)CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Giuseppe M. C. Rosano
    • 1
    • 2
    Email author
  • Cristiana Vitale
    • 2
  • Massimo Fini
    • 2
  1. 1.Cardiovascular and Cell Sciences Research InstituteSt George’s University of LondonLondonUK
  2. 2.Centre for Clinical and Basic Research, Department of Medical SciencesIRCCS San Raffaele PisanaRomeItaly

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