CHICAGO – Testosterone replacement therapy in mobility-impaired, sedentary older men with low testosterone levels improved two different measures of aerobic capacity in a placebo-controlled, randomized 6-month clinical trial.
The age-related decline in peak oxygen uptake during exercise, or peak VO2, was 3.4-fold less in the testosterone-treated men than would be expected based on published population norms. Moreover, the rate of decline in peak VO2 in placebo-treated controls was nearly twice the expected rate for the age-matched general population; this accelerated decline was probably due to their limited mobility and low testosterone levels, Thomas W. Storer, Ph.D., said at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.
"This study is the first to show enhanced endurance performance as a result of testosterone therapy in men who have difficulty performing some physical tasks but are otherwise healthy. This is something we think is going to be clinically meaningful," said Dr. Storer, director of the exercise physiology and physical performance laboratory at Brigham and Women’s Hospital, Boston.
He presented an analysis of a subset of participants in the prospective, randomized Testosterone in Older Men With Mobility Limitation (TOM) trial, in which subjects with low total or free testosterone levels were placed on 10 mg/day of testosterone gel or placebo gel for 6 months. The subgroup consisted of 64 men, mean age 73, who underwent formal testing of aerobic capacity via measurement of changes over time in peak VO2 and gas exchange lactate threshold during symptom-limited exercise cycling.
The gas exchange lactate threshold is a good functional measure of the ability to do work over a prolonged period. The rate remained steady during the 6-month study in the testosterone-treated men but declined significantly – and to a greater-than-expected extent based on normative values – in the placebo-treated controls (see chart).
"We think the mechanisms involved in this benefit are many," Dr. Storer said in an interview. Among them are testosterone’s demonstrated ability to increase muscle mass and thereby generate more force during exercise; increased RBC formation; stimulation of tissue capillarity in order to allow more blood flow to the exercising muscle; and stimulation of mitochondrial biogenesis, which increases oxygen uptake by muscle tissue.
However, he added that although these results are quite promising, he doesn’t think this work is ready for prime time application in daily clinical practice. He plans to further evaluate the safety of this treatment and the durability of the effects in a study with larger patient numbers and longer treatment.
The study was funded by the National Institute on Aging, the Claude D. Pepper Older Americans Independence Center, and Boston University. Dr. Storer reported having no relevant financial conflicts.