Bioavailable testosterone levels appear to be associated with frailty in older men

In a new study, older men with low levels of bioavailable testosterone were more likely to be frail, suggesting that frailty status should be considered as an outcome in testosterone supplement trials.

Researchers conducting the Osteoporotic Fractures in Men (MrOS) study evaluated 1,469 community-dwelling men (mean age, 65 years) from six U.S. centers. Frailty status was reassessed in 1,245 of the men 4.1 years after enrollment.

The researchers defined frail as having three or more of the following: weakness, slowness, low activity, exhaustion and sarcopenia. Intermediate frail men had one or two of these criteria, and robust men had none. The researchers performed cross-sectional and longitudinal analyses to determine associations between frailty and estradiol, bioavailable estradiol, testosterone, bioavailable testosterone and sex hormone-binding globulins. Bioavailable testosterone was the only hormone associated with frailty in these analyses.

In age-adjusted models, the researchers observed a 48% increased risk for greater frailty status for men in the lowest quartile of total testosterone compared with men in the highest quartile of each sex hormone measure. However, this finding was no longer statistically significant after the researchers adjusted for BMI, self-rated health, education, smoking and certain medical conditions.

Men in the lowest quartile of bioavailable hormone had a 39% increased risk for greater frailty status compared with men in the highest quartile (OR=1.39; 95% CI, 1.02-1.91). This finding, based on cross-sectional analyses, was also observed after adjusting for age, body size, health status and medical conditions.

In age-adjusted longitudinal analyses at 4.1 years of follow-up, men in the lowest quartile of bioavailable testosterone were 1.51 times more likely to have a greater frailty status (95% CI, 1.10-2.07). However, after the researchers adjusted for confounding factors such as age, BMI, smoking and number of medical conditions, these men had only a modest increased risk (OR=1.32; 95% CI, 0.94-1.84).

Cawthon PM. J Clin Endocrinol Metab. 2009;94:3806-3815.