Editors' ChoiceEndocrinology

Testosterone Replacement Leaving Men Heartbroken

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Science Translational Medicine  27 Nov 2013:
Vol. 5, Issue 213, pp. 213ec197
DOI: 10.1126/scitranslmed.3008070

Over the past decade, prescriptions for testosterone therapy have increased to over 5 million, with a market of $1.6 billion a year in the United States alone. Although professional guidelines recommend limiting testosterone therapy to patients with symptomatic testosterone deficiency, testosterone is being increasingly misused or abused for power sports or bodybuilding and as a male anti-aging agent.

The benefits of testosterone replacement therapy have been well characterized and include, in addition to improved sexual function, an increase in bone density, increase in muscle mass and strength, and improved lipid profile and insulin sensitivity. Despite these positive effects, a recent trial of testosterone treatment in older men was unexpectedly discontinued because of increased cardiovascular events in the treatment group. A large retrospective analysis of more than 8000 men from the Veteran Affairs health care system contributed substantial evidence of cardiovascular-adverse effects associated with testosterone replacement. The authors analyzed a national cohort of men with low testosterone levels (<300 ng/dL) who underwent coronary angiography and compared the outcomes of all-cause mortality, myocardial infarction, and ischemic stroke in men treated or untreated with testosterone. The mean age of the study participants was 63 years, and the majority of men had comorbidities such as hypertension, dyslipidemia, diabetes, and obesity.

Three years after the baseline angiography, the incidence of the composite outcome was 19.9% among men who were not treated with testosterone and 25.7% among men who were prescribed testosterone, demonstrating a nearly 30% increased risk of adverse outcomes associated with testosterone treatment (hazard ratio 1.29; 95% confidence interval, 1.04 to 1.58, adjusted for the presence of coronary disease at baseline).

The authors concluded that in a cohort of men who underwent coronary angiography and had a low serum testosterone level, the use of testosterone therapy was associated with increased risk of mortality, myocardial infarction, and stroke, independent of prior cardiovascular disease. Although the findings may not apply to testosterone replacement in younger patients without comorbidities, these alarming findings call for caution, especially given the rapid increase in the number of testosterone prescriptions for adult men across all age groups.

R. Vigen et al., Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA 310, 1829–1836 (2013). [Abstract]

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