Testosterone Therapy and Cardiovascular Risks
As a professional society dedicated to the effective and safe treatment of individuals with sexual dysfunction and men’s health overall, the International Society for Sexual Medicine is aware of recent concerns regarding cardiovascular risks associated with the use of testosterone therapy. This concern stems from two journal articles, one published in November 2013 in the Journal of the American Medical Association (1), and the other published in January 2014 in the journal, Plos One (2). Neither of these reports was a planned experimental study with control groups and defined goals. Instead these were retrospective analyses of data collected for other reasons. These types of analyses are prone to bias and error, and results are often irreproducible (3). For this reason, this type of study is generally not used for medical decision-making, although in some cases these may prompt further investigation with an experimental study.
Review of both studies (click here for detailed analysis of these studies) reveals major flaws that render questionable the assertion that testosterone therapy increased cardiovascular (CV) risks. The suggestion of increased cardiovascular risk with these recent reports is contradicted by a large body of literature that strongly indicates CV risks in association with low testosterone levels, and beneficial effects of T therapy in improving risk factors for CV disease (4-7). Although an objective scientific approach must openly consider all new evidence, the ISSM does not find these new reports to provide credible evidence of increased CV risk with T therapy.
Testosterone deficiency (also called hypogonadism) is a medical condition recognized for over a century, associated with symptoms that include reduced sexual desire, erectile dysfunction, fatigue, depressed mood, reduced muscle mass, and increased fat. Research has shown that T deficiency is also associated with a number of significant health issues, such as diabetes, obesity, the metabolic syndrome, and bone fractures (6). Several longitudinal population-based studies have demonstrated reduced longevity in men with low T levels (8-11). Treatment of T deficiency improves symptoms as well as several indicators of general health. Testosterone therapy is only indicated in men with characteristic symptoms or signs as well as documented low testosterone levels.
Like all treatments, T therapy has risks (12). The most common are erythrocytosis (increased production of red blood cells), acne, gynecomastia (breast enlargement), and fluid retention. The historical concern that T therapy promotes prostate cancer appears to be unfounded (13). The current evidence does not support the assertion that T therapy increases the risk of heart attacks, stroke, or other cardiovascular risks.
There is no reason to change the current management of men with testosterone deficiency on the basis of these recent articles. Men currently being treated for testosterone deficiency with testosterone therapy and experiencing benefits may continue treatment. Men diagnosed with testosterone deficiency should consider treatment with testosterone therapy after full discussion with their healthcare provider. Testosterone therapy provides significant benefits for men with sexual symptoms, and also for a variety of non-sexual symptoms. Like all medical treatments, testosterone therapy is associated with risks, and these should be discussed with one’s healthcare provider. Weighing the entirety of available medical research, there is no compelling evidence that testosterone therapy increases cardiovascular risks.
1. Vigen R, O’Donnell CI, Barón AE, Grunwald GK, Maddox TM, Bradley SM, Barqawi A, Woning G, Wierman ME, Plomondon ME, Rumsfeld JS, Ho PM. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310:1829-1836.
2. Finkle WD, Greenland S, Ridgeway GK, Adams JL, Frasco MA, Cook MB, Fraumeni Jr JF, Hoover RN. Increasing Risk of Non-Fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men. PLoS ONE 9(1): e85805. Doi: 10.1371/journal.pone.0085805
3. Ioannidis, J. P. A. Contradicted and initially stronger effects in highly cited clinical research. Journal of the American Medical Association, 2005; 294, 218–228.
4. Oskui PM, French WJ, Herring MJ, Mayeda GS, Burstein S, Kloner RA. Testosterone and the cardiovascular system: a comprehensive review of the clinical literature. J Am Heart Assoc. 2013 Nov 15;2(6):e000272
5. Carson CC and Rosano G. Exogenous testosterone, cardiovascular events, and cardiovascular risk factors in elderly men: A review of trial data. J Sex Med 2012;9:54–67.
6. Traish AM, Miner M, Zitzmann M, Morgentaler A. Testosterone deficiency. Am J Medicine, 124, 578-587, 2011.
7. Aversa A, Bruzziches R, Francomano D, Rosano G, Isidori AM, Lenzi A, and Spera G. Effects of testosterone undecanoate on cardiovascular risk factors and atherosclerosis in middleaged 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.
8. Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR. Low serum testosterone and mortality in male veterans. Arch Intern Med. 2006;166:1660–1665.
9. Laughlin GA, Barrett-Connor E, Bergstrom J. Low serum testosterone and mortality in older men. J Clin Endocrinol Metab. 2008;93:68–75.
10. 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.
11. 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.
12. Rhoden EL, Morgentaler A: Risks of testosterone-replacement therapy and recommendations for monitoring. N Engl J Med 350:482-92, 2004.
13. Khera M, Crawford D, Morales A, Salonia A, Morgentaler A. A New Era of Testosterone and Prostate Cancer: From Physiology to Clinical Implications. Eur Urol. Epub 2013 Aug 16.