Most aging individuals die from atherosclerosis, cancer, or dementia; but in the oldest old, loss of muscle strength resulting in frailty is the limiting factor for an individual's chances of living an independent life until death. Three hormonal systems show decreasing circulating hormone concentrations during normal aging: (i) estrogen (in menopause) and testosterone (in andropause), (ii) dehydroepiandrosterone and its sulphate (in adrenopause), and (iii) the growth hormone/insulin-like growth factor I axis (in somatopause). Physical changes during aging have been considered physiologic, but there is evidence that some of these changes are related to this decline in hormonal activity. Hormone replacement strategies have been developed, but many of their aspects remain controversial, and increasing blood hormone levels in aging individuals to those found during mid-adult life has not been uniformly proven to be safe and of benefit.

We characterized a BclI-RFLP (restriction fragment length polymorphism) of the GR gene as a C/G polymorphism in intron 2 of which the G-allele was associated with hypersensitivity to glucocorticoids. This resulted in a lower BMI in older individuals in general, while our study in elderly males suggests that the lower BMI is probably due to a greater loss of lean mass during the ageing process.

Background-The burden of atherosclerosis especially afflicts the increasing older segment of the population. Recent evidence has emphasized a protective role of endogenous sex hormones in the development of atherosclerosis in aging men. Methods and Results-We studied the association between endogenous sex hormones and progression of atherosclerosis in 195 independently living elderly men. Participants underwent measurements of carotid intima-media thickness (IMT) at baseline in 1996 and again in 2000. At baseline, serum concentrations of testosterone (total and free) and estradiol (total and free E 2 ) were measured. Serum free testosterone concentrations were inversely related to the mean progression of IMT of the common carotid artery after adjustment for age (␤ϭϪ3.57; 95% CI, Ϫ6.34 to Ϫ0.80). Higher serum total and free E 2 levels were related to progression of IMT of the common carotid artery after adjustment for age (␤ϭ0.38; 95% CI, Ϫ0.11 to 0.86; and ␤ϭ0.018; 95% CI, Ϫ0.002 to 0.038, respectively). These associations were independent of body mass index, waist-to-hip ratio, presence of hypertension and diabetes, smoking, and serum cholesterol levels Conclusions-Low free testosterone levels were related to IMT of the common carotid artery in elderly men independently of cardiovascular risk factors.

In a population of independently living elderly men, higher FT4 and rT3 concentrations are associated with a lower physical function. High serum rT3 may result from a decreased peripheral metabolism of thyroid hormones due to the aging process itself and/or disease and may reflect a catabolic state. Low serum FT4 is associated with a better 4-yr survival; this may reflect an adaptive mechanism to prevent excessive catabolism.