Positive effects of testosterone treatment in elderly, frail men

Short-term testosterone treatment appeared to prevent age-associated loss of lower limb strength and improve body composition and quality of life for elderly, frail men with borderline low testosterone levels.

Researchers conducted a randomized, double blind, placebo-controlled, parallel-group, single-center study to examine the effects of testosterone treatment. The study included men aged 65 years and older with a baseline testosterone level <12 nmol/L or free testosterone <250 pmol/L.

The researchers randomly assigned 138 men to daily 50 mg transdermal testosterone and 136 men to daily placebo gel for six months. Mean total and free testosterone levels reached the target range within 10 days and were maintained during the treatment period; doses were adjusted for patients assigned to transdermal testosterone when levels were outside the target range of 18 nmol/L to 30 nmol/L.

At six months, isometric knee extension peak torque improved in the testosterone group by 4.7 nm but decreased by 4.7 nm in the placebo group; the mean adjusted difference was 8.6 nm (95% CI, 1.3-16). This finding “is recognized as functionally significant; an increase in knee extension peak torque of around 5 nm has been showed to be associated with improvements in physical function,” the researchers wrote.

Men assigned to testosterone had a greater increase in lean body mass (1.08 kg) compared with men assigned placebo (mean difference=1.1 kg; 95% CI, 0.6-1.5). Fat mass decreased significantly in the testosterone group (0.9 kg) compared with the placebo group.

The researchers reported improvements in physical function and quality of life among men assigned to testosterone. Their scores, measured by the Aging Males’ Symptoms scale (somatic, psychological and sexual domain symptom) decreased more than the placebo group; somatic scores decreased by –1.2 (95% CI, –2.4 to –0.04) and sexual symptom scores by –1.3 (95% CI, –2.5 to –0.2).

No differences were observed in Tinetti gait and balance, aggregate locomotor function, six-minute walk or physical performance tests.

Prostate-specific antigen levels increased from 1.5 ng/mL at baseline to 2 ng/mL at six months in the testosterone group; the researchers observed no change in the placebo group. Four men had elevated prostate-specific antigen levels during treatment and were referred for urological assessment; their levels decreased after stopping treatment. There were six serious adverse events in the testosterone group: lung cancer, esophagus cancer, pulmonary embolism, heart failure, abdominal aneurysm and constrictive pericarditis.

Testosterone and frailty

In an accompanying editorial, Shalender Bhasin, MD, said these data confirm that testosterone therapy is associated with improvements in skeletal muscle mass and strength, but the improvements are not translated into functional improvements. The improvements observed in skeletal mass and strength were relatively small in this study, and testosterone therapy may not be a viable, functional solution.

“Because gains in skeletal muscle mass and strength are correlated with testosterone dose and testosterone concentrations, it may be necessary to raise serum testosterone concentrations to even higher levels that those achieved in this trial to realize clinically meaningful gains in muscle mass and strength; the long-term safety of such an approach remains to be demonstrated,” Bhasin, of the section of endocrinology, diabetes and nutrition at Boston University School of Medicine, wrote in the editorial.

“Translation of muscle mass and strength gains into physical function improvements may require additional neuromuscular, cognitive and behavioral adaptations that are not induced by testosterone administration alone,” he said.

Bhasin said few therapeutic options are available to treat older, frail men with functional limitations and physical disability, and there is the need for pharmacological function-promoting therapies. He wrote in favor of further research, particularly in the field of promyogenic function-promoting therapies such as selective androgen receptor modulators, myostatin antagonists and growth hormone secretagogues, and that a study examining the effects of testosterone on mobility limitation would be an example of physical function improvement. – by Matthew Brannon

Srinivas-Shankar U. J Clin Endocrinol Metab. 2010;95:639-650.

Bhasin S.J Clin Endocrinol Metab. 2010;95:509-511.