Frailty and its relationship to late onset hypogonadism

The vulnerable health status usually preceding the onset of overt disability is often referred to as frailty. A stringent definition is elusive, but it may be viewed as a physiological syndrome, characterised by decreased reserve and diminished resistance to stressors, resulting from cumulative decline across multiple physiological systems and causing vulnerability to adverse outcomes. Many elements of frailty are related to the neurological system, metabolism, joints, bones and muscles. Central to frailty is the dramatic decline in muscle mass and strength with ageing. Therefore, sarcopenia seems to be the major determinant of frailty.Several components of the frailty syndrome are related to the physiological actions of testosterone. Testosterone also has effects on psychological functioning. Testosterone (or its aromatisation product oestradiol) is required for the maintenance of bone mineral density. Testosterone also stimulates red blood cell formation.Testosterone thus has a profound effect on body composition. A significant characteristic of ageing and a factor in frailty is the loss of muscle mass and the increase in fat mass. Androgens promote differentiation of mesenchymal multipotent cells into the myogenic lineage and inhibit their adipogenic differentiation, thus reversing the development of a downward spiral of loss of muscle mass and increase in fat mass. Skeletal muscles of older men are as responsive to the anabolic effects of testosterone as those of younger men, indicating that age as such should not be an impediment to elderly men benefiting from the anabolic effects of testosterone. So, while frailty is obviously a complex syndrome, some elements are androgen-associated and these may improve in men with subnormal testosterone levels.