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Testosterone therapy leads to ‘modest’ improvement in walking distance, ability

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November 29, 2018

Despite negative findings from the physical function substudy of the Testosterone Trials, or T Trials, researchers conducting a secondary analysis of data from the entire T Trials cohort found greater evidence that walking ability and walking distance for older men with low testosterone levels may be improved by testosterone therapy.

“In the primary T Trials analysis, for men who were enrolled in the [Physical Function Trial, 6-m walk test] distance did not improve ... significantly more frequently in the testosterone group than in the placebo group,” Shalender Bhasin, MBBS, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital, and colleagues wrote. “However, in the prespecified analyses that included all men in the T Trials, a significant difference between treatment groups in the proportion of men with improved [6-m walk test distance] was identified, showing a benefit in men treated with testosterone. These findings led us to investigate the effects of testosterone in the T Trials participants who were not enrolled in the [Physical Function Trial], and to assess whether the baseline characteristics defining eligibility for the [Physical Function Trial] were related to treatment response.”

Participants in the overall study population (n = 790) were aged at least 65 years and had low testosterone at baseline (mean fasting testosterone, < 9.5 nmol/L). Nearly half of the total population was included in the physical function trial (n = 390), which required self-reported mobility limitation (difficulty walking one-quarter mile or up a flight of stairs) and 6-minute walking speeds of less than 1.2 m per second.

All participants were recruited between April 2011 and June 2014 and were randomly assigned to one of two groups. The first group (n = 395) was asked to apply a gel with 50 mg testosterone on the skin once per day for a year. The second group (n = 395) was given a placebo gel. A total of 193 participants in the physical function trial were assigned by minimization randomization to the testosterone group while 197 participants were randomly assigned to the control group.

Participants were assessed for serum testosterone concertation at 1, 2, 3, 6 and 9 months, and in the testosterone group, dose was adjusted to maintain testosterone level between 500 ng/dL and 800 ng/dL. Six-minute walking speed was measured and self-reported physical function was collected at baseline and 3, 6, 9 and 12 months; fall events were determined by self-reporting every 3 months.


In the overall T Trials cohort, the change in 6-minute walking distance increased for men receiving testosterone treatment (treatment effect, 6.69 m; 95% CI, 1.8-11.57) compared with the placebo group. More men in the testosterone group also improved their 6-minute walking distance by at least 50 m (treatment effect, 1.77; 95% CI, 1.21-2.58) than those in the placebo group. Despite these findings, no significant difference was found in 6-minute walking distance between the two groups in the physical function trial.

The researchers observed that men in the testosterone treatment group with a baseline walking speed of at least 1.2 m per second were more likely to exhibit a significant improvement in walking speed after treatment (treatment effect, 14.2 m; 95% CI, 6.5-21.9) compared with those with slower baseline speeds (treatment effect, 3.5 m; 95% CI, –2.6 to 9.7). There was also a significant effect of testosterone treatment on 6-minute walking distance in men who identified baseline mobility limitations (treatment effect, 7.6 m; 95% CI, 1-14.1).

“The significant interaction between baseline gait speed and treatment group suggests that the effect of baseline gait speed on response to testosterone is likely to be real,” the researchers wrote. “It is possible that men with better baseline physical function, compared with those with poor function at baseline, might engage in a higher level of physical activity or might have greater gains in muscle mass, which subsequently contribute to a greater treatment effect.”

In the physical function trial, participants in the testosterone treatment group reported significantly better mobility (treatment effect, 2.8; 95% CI, 0.41-5.2) than those in the placebo group. Similar improvements in mobility were found in the overall testosterone group (treatment effect, 3.42; 95% CI, 1.66-5.18). These improvements were noted for both men with 6-minute walking speeds of at least 1.2 m per second (treatment effect, 4.9; 95% CI, 2.2-7.7) and those with slower gait speeds (treatment effect 2.5; 95% CI, 0.29-4.6).

At 1 year, all participants in the testosterone group experienced a mean increase of total testosterone from 8 nmol/L at baseline to 17.9 nmol/L. The researchers noted that for every 3.5-nmol/L increase in testosterone, there was a 1-m increase in 6-minute walking distance (P = .0023).

“It is possible that the [6-minute walk test], which is more a measure of endurance than of lower-extremity strength, might be less responsive to testosterone than other measures of mobility such as the stair climbing power, which is more strongly associated with lower-extremity strength,” the researchers wrote.


Although mobility and walking distance were improved by testosterone therapy, the researchers did not find an influence on falls, noting the same number (n = 103) in each group in the overall trial populations.

“Testosterone administration in older men with mobility limitation consistently improved self-reported measures of physical function and modestly improved mobility, but did not affect fall frequency,” the researchers wrote. “These effects might not, by themselves, justify use of testosterone therapy in older men with low testosterone concentrations. Thus, testosterone therapy should probably not be started specifically to improve physical function, although men who are treated with testosterone for other reasons could have some improvement in physical function.”

In a commentary accompanying the study, Bradley D. Anawalt, MD, chief of medicine at the University of Washington Medical Center, and Stephanie T. Page, MD, PhD, Robert B. McMillen endowed professor of lipid research and a professor of metabolism, endocrinology and nutrition and medicine at the University of Washington, wrote that “modest” improvements from testosterone therapy could still have significantly beneficial effects.

“It is not clear what constitutes clinically significant changes in mobility, and small differences might be important. The 6-min walk test has been prospectively correlated with mortality, and fairly small differences in gait speed ... are associated with significant differences in mortality,” Anawalt and Page wrote, adding that future research could better determine the efficacy of testosterone treatment. “Because it is unclear whether the effects of testosterone and exercise are additive in older men, future studies should examine the mobility and body composition effects of testosterone plus exercise versus placebo plus daily exercise or usual lifestyle.” – by Phil Neuffer

Disclosures: Bhasin reports he received consultant fees from AbbVie, Novartis and Regeneron, and grant support from AbbVie, Metro International Biology, AliveGen, Abbott, Novartis, Regeneron and Transition Therapeutics. Please see the study for all other authors’ relevant financial disclosures.

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