Testosterone and Exercise in Middle-to-Older Aged Men: Combined and Independent Effects on Vascular Function.

The endothelium is integral to the maintenance of vascular health in humans, and advancing age and low testosterone levels are associated with endothelial dysfunction in men. We compared the impacts of testosterone and exercise training, alone and in combination, on endothelium-dependent flow-mediated dilation % and endothelium-independent glyceryl trinitrate % responses. In this 2×2 factorial 12-week randomized controlled trial, 80 men aged 50 to 70 years with waist girth ≥95 cm and low-normal serum testosterone levels (6-14 nmol/L) were randomized to transdermal AndroForte5 (testosterone 5.0% w/v, 100 mg/2 mL; testosterone), or matching placebo; and to supervised centre-based exercise or no additional exercise. Testosterone increased serum testosterone levels (testosterone×time, P=0.003) to the extent that 62% of subjects in testosterone groups increased levels to >14 nmol/L, whereas placebo treatment had no impact on testosterone levels. Exercise training increased flow-mediated dilation % (exercise×time, P=0.033; testosterone+exercise: +0.5, placebo+exercise: +1.0 versus testosterone+no additional exercise: -0.7, placebo+no additional exercise: +0.2%), whereas testosterone did not impact flow-mediated dilation, nor was it additive to exercise (all P>0.05). There were no significant exercise or drug main effects on glyceryl trinitrate responses (all P>0.05). Exercise training improved endothelium-dependent vasodilator function, whereas administration of testosterone at therapeutic doses did not impact flow-mediated dilation % or add to the exercise benefit. Vascular smooth muscle sensitivity to nitric oxide was not modified by exercise, testosterone, or their combination. In middle-to-older-aged men with central adiposity and low/normal testosterone levels, we observed no evidence that testosterone added to the beneficial impact of exercise on vascular function and health. REGISTRATION: URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368611; Unique identifier: ACTRN12615000600549.