Androgen deficiency as a biological determinant of frailty: hope or hype?

The role of androgen deficiency as a biological determinant of frailty has received considerable attention. Cross-sectional studies have shown that low bioavailable testosterone (BT) is associated with prevalent frailty. High levels of luteinizing hormone and sex hormone binding globulin are also associated with prevalent frailty. Longitudinal studies have had mixed results, suggesting, for the most part, that a decline in BT over time is associated with progression of frailty. A number of potential biases were found in the current body of evidence, including misclassification bias (due to testosterone assays that were insensitive in lower ranges), selection bias (due to preferential inclusion of healthier individuals), and residual confounding (due to correlation of low testosterone with several disease states and adverse health characteristics). Consideration of these biases is vital to ensure that future epidemiological studies and interventional trials generate valid conclusions.