New Horizons: Testosterone or Exercise for Cardiometabolic Health in Older Men

Abstract

Abstract Middle-aged and older men have typically accumulated comorbidities, are increasingly sedentary, and have lower testosterone concentrations (T) compared to younger men. Reduced physical activity (PA) and lower T both are associated with, and may predispose to, metabolically adverse changes in body composition, which contribute to higher risks of cardiometabolic disease. Exercise improves cardiometabolic health, but sustained participation is problematic. By contrast, rates of T prescription have increased, particularly in middle-aged and older men without organic diseases of the hypothalamus, pituitary, or testes, reflecting the unproven concept of a restorative hormone that preserves health. Two recent large randomized trials of T, and meta-analyses of randomized trials, did not show a signal for adverse cardiovascular (CV) events, and T treatment on a background of lifestyle intervention reduced type 2 diabetes by 40% in men at high risk. Men with both higher endogenous T and higher PA levels have lower CV risk, but causality remains unproven. Exercise training interventions improve blood pressure and endothelial function in middle-aged and older men, without comparable benefits or additive effects of T treatment. Therefore, exercise training improves cardiometabolic health in middle-aged and older men when effectively applied as a supervised regimen incorporating aerobic and resistance modalities. Treatment with T may have indirect cardiometabolic benefits, mediated via favorable changes in body composition. Further evaluation of T as a pharmacological intervention to improve cardiometabolic health in aging men could consider longer treatment durations and combination with targeted exercise programs.