Testosterone and Cardiovascular Diseases: Causes or Consequences: The Lesson from the Last 5 Years

Abstract

The relationship between the age-dependent decline of testosterone (T) and cardiovascular (CV) risk in men is still a matter of intense debate. In particular, over the last 5 years, several scientific reports have shed a new negative light on the association between T treatment (TTh) and forthcoming CV diseases (CVD). Based on this evidence, the US Food and Drug Administration agency has recommended that all T supplementations carry a warning that they may increase the risk of heart attack and stroke. To better clarify the available data on this topic, we scrutinized and summarized, also by using meta-analytic methods, the data generated during the last 5 years, as derived from the analysis of observational (either longitudinal or pharmaco-epidemiological) studies and from randomized controlled trials (RCTs) on TTh and CVD risk. Our analysis shows that there is a clear association between baseline T deficiency and overall mortality and CVD-related mortality when longitudinal surveys were analyzed, although a specific pathogenetic link cannot be made. When interventional trials were studied, several but not all pharmaco-epidemiological studies reported a possible protective role of TTh on CV risk; however, data from RCTs and their meta-analysis, presented here, do not provide us with sufficient information on this point. Present data do not indicate an increased risk with TTh, but there is also insufficient definitive evidence that TTh is protective. Therefore, further and more specific trials are advisable to better clarify the possible relationship between low T, TTh, and CVD in aging men.