Abstract 13220: Cardiovascular Impact of Testosterone Therapy in Men with Low Testosterone Levels

Abstract

Introduction: Epidemiologic studies have identified low testosterone (T) levels as an independent risk factor for cardiovascular (CV) and total mortality. However, the impact of T therapy on CV outcomes is controversial. A small trial in older men at high risk was stopped early due to increased CV events (NEJM 2010; 363:109). A recent observational study in veterans suggested modest risk (JAMA 2013; 3310:1829). We sought to assess the impact of T supplementation and achieved T levels across Intermountain Healthcare (IHC) facilities using a virtual controlled study design. Methods: IHC electronic medical records were searched between 1996 and 2011 to identify subjects who had a low initial total T level, a subsequent T level, and ≤3y follow-up. Levels were correlated with T supplement use. Primary outcomes were a composite of death, nonfatal myocardial infarction, and stroke (MACE) and death alone (D). Hazard ratios (HRs) comparing groups of persistent low (<212 ng/dL, n=1142), normal (212-742 ng/dL, n=2634), and high (>742 ng/dL, n=1919) achieved T were calculated by Cox regression, adjusting for 17 baseline variables. Results: A total of 5,695 men (age 62.3 ± 9.3 y, diabetes: 28%, CAD: 22%) were studied. Event rates at 1 and 3-y by T level, and adjusted HRs, are shown in the Table. Overall 3-y rates of MACE and D were 8.6% and 6.4%, respectively. Subjects supplemented to normal/high T had reduced 3-y MACE (HR 0.55, 95% CI 0.46-0.67) and D (HR 0.43, CI 0.35-0.54) compared to persistent low T subjects, with no signal for effect attenuation for MACE or D with higher T. Results were similar for 1-y MACE (HR 0.51, p<0.0001) and D (HR 0.38, p<0.0001). Conclusions: In a large general healthcare population, T therapy in men with low T was associated with reduced MACE and D over 3-y compared to no or ineffective supplementation. Resolving the difference in CV risk impact of T therapy between this, and previous studies, warrants a large randomized clinical trial in a similar, younger population.