The relationship between testosterone deficiency and frailty in elderly men.

The vulnerable health status usually preceding the onset of overt disability is often referred to as frailty. A stringent definition is elusive but it can be viewed as a physiological syndrome, characterized by decreased reserve and diminished resistance to stressors, resulting from a cumulative decline across multiple physiological systems and causing vulnerability to adverse outcomes. Elements of frailty are related to the neurological system, metabolism, joints, bones, and muscles. Sarcopenia seems to be the major determinant of frailty. Several components of the frailty syndrome are related to loss of physiological actions of testosterone (T). T and/or its aromatized metabolite, estradiol, are necessary for maintenance of bone mineral density. Furthermore, T stimulates erythrocyte formation. T has a profound effect on body composition. Androgens promote differentiation of mesenchymal pluripotent cells into the myogenic lineage and inhibit differentiation into the adipogenic lineage. Skeletal muscles of older men are as responsive to the anabolic effects of T as of younger men. Thus, although frailty is obviously a complex syndrome, some elements are androgen-associated and these can improve in men with subnormal T levels when treated with T. Evidence suggests that T treatment in frail elderly men with low T improves body composition, quality of life, and physical function, including increased axial bone mineral density and body composition. The data available to date strongly suggest a relationship between T-deficiency and frailty and warrant further basic and clinical investigations to extend these observations to the management of elderly men with frailty.