Do androgens play any role in the physical frailty of ageing men?

The term frailty describes an age-related state of vulnerable health. The aetiology of this condition is not well understood. A number of mechanisms may contribute to frailty. Amongst these is the possible influence of age-related perturbations of sex hormones, particularly, the fall in testosterone in ageing men. This declining androgenic function has been thought to contribute to the loss of muscle mass (sarcopaenia) and strength that occurs with ageing and thereby underpin the development of frailty. Testosterone replacement has therefore been suggested as a possible intervention to treat frailty. This review summarizes evidence from observational and interventional studies on the effects of testosterone on frailty and its key components including body composition, muscle strength and physical function. Evidence from these studies is considered against study design, methodological issues and in the context of the current understanding of frailty. The role of androgens in the development of frailty and their utility in treating this condition are evaluated. Future research directions for the use of androgens in the treatment of frailty are suggested. The potential interaction between testosterone and other frailty mechanisms and the possibility that secondary components of the sex hormone system may be appropriate frailty biomarkers are also discussed.