Testosterone, cardiovascular disease and the metabolic syndrome.

Recent evidence suggests that low, rather than high, testosterone (T) is associated with increased male morbidity and mortality. We reviewed relationships between hypogonadism, metabolic syndrome (MetS) and cardiovascular (CV) disease (CVD), along with erectile dysfunction (ED), a common condition in the three diseases. Although several experimental data indicate that T exerts a protective effect on vascular function, epidemiological studies do not support a link between hypogonadism and CVD and three meta-analyses found no significant effect of testosterone replacement therapy (TRT) on CV events. Low T is associated with increased risk of CV death in community-dwelling men, and in men with ED. It is possible that both low T and CVD are associated with another, still unknown (or not assessed) factor, thus explaining the association, in the absence of any causal relationship. A meta-analysis on the effect of TRT in MetS-associated hypogonadism demonstrated positive effects of T on some of the components of MetS. Large-scale interventional studies with TRT are therefore advisable.