Association of Testosterone Replacement With Cardiovascular Outcomes Among Men With Androgen Deficiency: Expert Commentary

As men get older, starting at the age of 30 years, their testosterone levels decrease by an average of 3.1 to 3.5ng/dL per year1. Low levels of testosterone can lead to androgen deficiency, symptoms which include: loss of sexual desire, erectile dysfunction, breast enlargement or tenderness, hot flashes, reduced energy, irritability, and depressed mood. Exogenously administered testosterone, or testosterone replacement therapy (TRT) is used to treat androgen deficiency2; Some studies have shown an increase in cardiovascular  (CV) adverse events when using TRT3-5, while others show that TRT may have CV benefits6-8. The primary goal of this study was to view more closely the association between TRT and CV outcomes in androgen deficient men. 

This was a retrospective cohort study that looked at men at least 40 years old between January 1, 1999 and December 31, 2010, with evidence of androgen deficiency, either by coded diagnosis or serum testosterone testing. The cohort was then followed-up to the first 90, 180, and 365 days through December 31, 2012, and was classified into ever-TRT or never-TRT groups. The primary outcome was c omposite of 4 CV events: (1) acute myocardial infarction, (2) unstable angina, (3) combined stroke, and (4) sudden cardiac death. Baseline conditions and comorbidities were accounted for and controlled. For statistical analysis, a multivariable Cox proportional hazards model was used. 

In total, 129, 544 were identified in the study and 44,335 of these men met inclusion and exclusion criteria. The cohort consisted of 8808 men in the ever-TRT group and 35,527 men in the never-TRT group. The rates of the composite cardiovascular end point were 23.9 vs 16.9 per 1000 person in the never-TRT and ever-TRT groups, respectively. The adjusted hazard ratio (HR) for the composite cardiovascular end point in the ever-TRT group was 0.67. When outcome was restricted to combine stroke and cardiac events, similar scores of 0.72 and 0.66 were seen, respectively.

In conclusion, the results of the study showed that TRT was associated with a lower risk of CV events, which are consistent with other studies9-11. In addition, it is recommended that men with hypogonadism be receiving TRT, as they are other plentiful of health benefits. Some limitations that the authors note was the criteria for identifying androgen-deficient males did not meet strict criteria and therefore by misclassified as androgen-deficient, and the observational nature of the study. 

Written by: Zhamshid Okhunov, MD Department of Urology, University of California, Irvine Urology

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