Exercise, Not Testosterone Therapy Can Improve Vascular Function in Aging Men

Daniel J. Green, PhD

New insights from a 12-week trial of middle-aged and older men on testosterone therapy suggest testosterone therapy has no beneficial effect on vascular health or function.

While some have theorized testosterone therapy could counteract the effects of aging on arteries, results of the trial indicate improvements in artery health and function were linked to increased physical activity and not testosterone therapy.

"The global increase in testosterone use has been very large, particularly among middle-aged and older men who might see it as a restorative hormone to increase energy and vitality," said lead investigator Daniel J. Green, PhD, Winthrop Professor and cardiovascular exercise physiology researcher in the School of Human Sciences at The University of Western Australia in Perth, in a statement. "However, previous studies are mixed as to whether replacement testosterone is beneficial or not, or whether it provides additional benefit over and above the effects of an exercise program."

With an interest in further understanding the effects of testosterone therapy in aging men, Green and a team of colleagues designed the current study to assess the impact of testosterone versus exercise training on endothelium-dependent flow-mediated dilation percentage and endothelium-independent glyceryl trinitrate percent responses. Designed as a 2x2 factorial randomized controlled trial, the 12-week study enrolled 80 men between 50-70 years of age with a waist girth of 95 centimeters or more and low to normal serum testosterone levels.

In total, 78 patients were included in the final analysis and underwent randomization. Of these 78, 21 were randomized to topical testosterone and a strutted exercise program, 18 were randomized to testosterone with no exercise, 20 were randomized to placebo therapy and no exercise, and 19 were randomized to placebo therapy with exercise. Of note, those randomized to testosterone therapy received 5% testosterone cream.

Investigators pointed out prescreening questionnaires allowed for the exclusion of patients based on smoking status, history of cardiovascular disease, and other factors. Additional inclusion criteria included having a fasting serum total testosterone of 6-14 nmol/L, a total cholesterol of 7 mmol/L or more, and a minimum eGFR of 45 ml/min.

Upon analysis, results indicated serum testosterone levels increased beyond 14 nmol/L among 62% of those randomized to testosterone therapy. Results also indicated exercise training was associated with increased flow-mediated dilation percent (P=.033; testosterone and exercise: +0.5, placebo and exercise: +1.0 versus testosterone and no additional exercise: −0.7, placebo and no additional exercise: +0.2%), while this effect was not apparent among those receiving testosterone therapy and it was not additive to exercise (P >.05).

Additionally, there were no significant exercise or drug main effects on glyceryl trinitrate responses (P >.05). Further analysis suggested exercise training was associated with improved endothelium-dependent vasodilator function, but testosterone therapy did not appear to influence flow-mediated dilation percent or add to the benefit of exercise. Investigators highlighted vascular smooth muscle sensitivity to nitric oxide was not modified by exercise, testosterone, or their combination.

“The results of our study suggest that if you are a healthy but relatively inactive middle-aged or older man with increased abdominal girth, and you are worried about your risk of heart attack, stroke or diabetes, then an exercise program with some support and supervision can help to improve the function and health of your arteries,” Green said. “Testosterone therapy may have some benefits, for example in increasing muscle mass in the legs, however, we didn’t find any benefits in terms of artery function, which is a determinant of future cardiovascular risk.”

This study, “Testosterone and Exercise in Middle-to-Older Aged Men,” was published in Hypertension.