Testosterone Replacement Therapy and the Cardiovascular System

Coronary Heart Disease (S. Virani and S. Naderi, Section Editors)
First Online:
Part of the following topical collections:
  1. Topical Collection on Coronary Heart Disease

Abstract

As testosterone replacement therapy (TRT) has emerged as a commonly prescribed therapy for symptomatic low testosterone, conflicting data have been reported in terms of both its efficacy and potential adverse outcomes. One of the most controversial associations has been that of TRT and cardiovascular morbidity and mortality. This review briefly provides background on the history of TRT, the indications for TRT, and the data behind TRT for symptomatic low testosterone. It then specifically delves into the rather limited data for cardiovascular outcomes of those with low endogenous testosterone and those who receive TRT. The available body of literature strongly suggests that more work, by way of clinical trials, needs to be done to better understand the impact of testosterone and TRT on the cardiovascular system.

Keywords

Testosterone Cardiovascular disease Male hormone therapy Androgens 
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Notes

Compliance with Ethical Standards

Conflict of Interest

Sahar Naderi declares no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Baillargeon J, Urban RJ, Ottenbacher KJ, Pierson KS, Goodwin JS. Trends in androgen prescribing in the United States, 2001 to 2011. JAMA Internal Medicine. 2013;173:1465–6.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Morales A. The long and tortuous history of the discovery of testosterone and its clinical application. J Sex Med. 2013;10:1178–83.CrossRefPubMedGoogle Scholar
  3. 3.
    Dotson JL, Brown RT. The history of the development of anabolic-androgenic steroids. Pediatr Clin North Am. 2007;54:761–9. xi.CrossRefPubMedGoogle Scholar
  4. 4.
    Edelstein D, Dobs A, Basaria S. Emerging drugs for hypogonadism. Expert Opin Emerg Drugs. 2006;11:685–707.CrossRefPubMedGoogle Scholar
  5. 5.
    Zitzmann M, Nieschlag E. Hormone substitution in male hypogonadism. Mol Cell Endocrinol. 2000;161:73–88.CrossRefPubMedGoogle Scholar
  6. 6.
    Ross RJ, Jabbar A, Jones TH, Roberts B, Dunkley K, Hall J, et al. Pharmacokinetics and tolerability of a bioadhesive buccal testosterone tablet in hypogonadal men. Eur J Endocrinol. 2004;150:57–63.CrossRefPubMedGoogle Scholar
  7. 7.•
    Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95:2536–59. This article outlines the current guidelines for testosterone therapy from the Endocrine Society.CrossRefPubMedGoogle Scholar
  8. 8.
    Wu FC, Tajar A, Pye SR, Silman AJ, Finn JD, O’Neill TW, et al. Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: The European Male Aging Study. J Clin Endocrinol Metab. 2008;93:2737–45.CrossRefPubMedGoogle Scholar
  9. 9.
    Hall SA, Esche GR, Araujo AB, Travison TG, Clark RV, Williams RE, et al. Correlates of low testosterone and symptomatic androgen deficiency in a population-based sample. J Clin Endocrinol Metab. 2008;93:3870–7.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Brambilla DJ, O’Donnell AB, Matsumoto AM, McKinlay JB. Intraindividual variation in levels of serum testosterone and other reproductive and adrenal hormones in men. Clin Endocrinol (Oxf). 2007;67:853–62.CrossRefGoogle Scholar
  11. 11.
    Paduch DA, Polzer PK, Ni X, Basaria S. Testosterone replacement in androgen-deficient men with ejaculatory dysfunction: a randomized controlled trial. J Clin Endocrinol Metab. 2015;100:2956–62.CrossRefPubMedGoogle Scholar
  12. 12.
    Bolona ER, Uraga MV, Haddad RM, Tracz MJ, Sideras K, Kennedy CC, et al. Testosterone use in men with sexual dysfunction: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clin Proc. 2007;82:20–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Srinivas-Shankar U, Roberts SA, Connolly MJ, O’Connell MD, Adams JE, Oldham JA, et al. 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;95:639–50.CrossRefPubMedGoogle Scholar
  14. 14.
    Araujo AB, Dixon JM, Suarez EA, Murad MH, Guey LT, Wittert GA. Clinical review: endogenous testosterone and mortality in men: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2011;96:3007–19.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Ruige JB, Mahmoud AM, De Bacquer D, Kaufman JM. Endogenous testosterone and cardiovascular disease in healthy men: a meta-analysis. Heart. 2011;97:870–5.CrossRefPubMedGoogle Scholar
  16. 16.
    Levine GN, D’Amico AV, Berger P, Clark PE, Eckel RH, Keating NL, et al. Androgen-deprivation therapy in prostate cancer and CV risk: a science advisory from the American Heart Association, American Cancer Society, and American Urological Association: Endorsed by the American Society for Radiation Oncology. CA Cancer J Clin. 2010;60:194–201.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Keating NL, O’Malley A, Freedland SJ, Smith MR. Diabetes and CV disease during androgen deprivation therapy: observational study of veterans with prostate cancer. J Natl Cancer Inst. 2012;104:1518–23.CrossRefPubMedGoogle Scholar
  18. 18.
    Saigal CS, Gore JL, Krupski TL, Hanley J, Schonlau M, Litwin MS, et al. Androgen deprivation therapy increases CV morbidity in men with prostate cancer. Cancer. 2007;110:1493–500.CrossRefPubMedGoogle Scholar
  19. 19.
    D’Amico AV, Denham JW, Crook J, Chen MH, Goldhaber SZ, Lamb DS, et al. Influence of androgen suppression therapy for prostate cancer on the frequency and timing of fatal myocardial infarctions. J Clin Oncol. 2007;25:2420–5.CrossRefPubMedGoogle Scholar
  20. 20.
    Efstathiou JA, Bae K, Shipley WU, Hanks GE, Pilepich MV, Sandler HM, et al. CV mortality after androgen deprivation therapy for locally advanced prostate cancer: Rtog 85-31. J Clin Oncol. 2009;27:92–9.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Levine GN, D’Amico AV, Berger P, Clark PE, Eckel RH, Keating NL, et al. Androgen-deprivation therapy in prostate cancer and CV risk: a science advisory from the American Heart Association, American Cancer Society, and American Urological Association: Endorsed by the American Society for Radiation Oncology. Circulation. 2010;121:833–40.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Nguyen PL, Je Y, Schutz FA, Hoffman KE, Hu JC, Parekh A, et al. Association of androgen deprivation therapy with cardiovascular death in patients with prostate cancer: a meta-analysis of randomized trials. JAMA. 2011;306:2359–66.CrossRefPubMedGoogle Scholar
  23. 23.
    Xu L, Freeman G, Cowling BJ, Schooling CM. Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials. BMC Med. 2013;11:108.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Basaria S, Harman SM, Travison TG, Hodis H, Tsitouras P, Budoff M, et al. Effects of testosterone administration for 3 years on subclinical atherosclerosis progression in older men with low or low-normal testosterone levels: a randomized clinical trial. JAMA. 2015;314:570–81.CrossRefPubMedGoogle Scholar
  25. 25.
    Vigen R, O’Donnell CI, Baron AE, Grunwald GK, Maddox TM, Bradley SM, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310:1829–36.CrossRefPubMedGoogle Scholar
  26. 26.
    Jones TH, Channer KS. Deaths and cardiovascular events in men receiving testosterone. JAMA. 2014;311:962–3.CrossRefPubMedGoogle Scholar
  27. 27.
    Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, et al. Adverse events associated with testosterone administration. N Engl J Med. 2010;363:109–22.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Finkle WD, Greenland S, Ridgeway GK, Adams JL, Frasco MA, Cook MB, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One. 2014;9:e85805.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Glueck CJ, Friedman J, Hafeez A, Hassan A, Wang P. Testosterone, thrombophilia, thrombosis. Blood Coagul Fibrinolysis. 2014;25:683–7.CrossRefPubMedGoogle Scholar
  30. 30.
    Glueck CJ, Goldenberg N, Budhani S, Lotner D, Abuchaibe C, Gowda M, et al. Thrombotic events after starting exogenous testosterone in men with previously undiagnosed familial thrombophilia. Transl Res. 2011;158:225–34.CrossRefPubMedGoogle Scholar
  31. 31.••
    Sharma R, Oni OA, Gupta K, Chen G, Sharma M, Dawn B, et al. Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men. Eur Heart J. 2015;36:2706–15. This is the most robust data to date on the association between testosterone therapy and myocardial infarction and mortality.CrossRefPubMedGoogle Scholar
  32. 32.
    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;97:2050–8.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Division of CardiologyStanford University Medical CenterStanfordUSA

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