Background: Previous clinical studies reported that testosterone replacement therapy unexpectedly increased cardiovascular (CV) events in elderly men, through an unknown underlying mechanism. Because nitric oxide (NO) production is reduced in elderly men, we hypothesized that testosterone exerts harmful CV effects under reduced NO production, and examined this hypothesis using a 2/3 nephrectomized triple neuronal/inducible/endothelial NO synthases (NOS)-knockout (NX-TKO) mouse model that causes death from myocardial infarction (MI).
Higa et al. (Thu,) studied this question.