Conclusions about testosterone therapy and cardiovascular risk.

In this issue of (AJA), several experts have reviewed the latest data on the potential and known effects of endogenous and exogenous testosterone (T) on cardiovascular risk. In the review by Meyer and Wittert, low endogenous serum T appears to be associated with higher risk of cardiovascular disease and overall mortality in certain populations such as Klinefelter syndrome and older men, but not in men with congenital hypogonadotropic hypogonadism. Whether this association is causal or whether low serum testosterone is a marker of other risk factors for cardiovascular disease such as obesity, diabetes mellitus, or other systemic disease is unknown. In Yeap's review of the relationship between circulating endogenous testosterone and its major metabolites, dihydrotestosterone, and estradiol, he raises the provocative hypotheses that there might be differential effects on cardiovascular and cerebrovascular risk related to endogenous testosterone and dihydrotestosterone concentrations. Based on the same epidemiological studies, Yeap postulates that there might be a U-shaped curve for circulating endogenous androgen concentrations such that lower and higher concentrations might confer greater risk of cardiovascular events and all-cause mortality than midrange concentrations. Shores demonstrates in a carefully done review of studies of large prescription databases (including >200 000 men) that testosterone therapy is not associated with overall mortality, myocardial infarction, stroke, or deep venous thrombosis events.