The effect of aging on the metabolic clearance rate and distribution of cortisol in man

Previous studies of cortisol kinetics in old people have been flawed. All but one used a large dose of unlabelled cortisol, which will itself alter the kinetic parameters, and in none was metabolic clearance rate (MCR) calculated. We have, therefore, injected [3H]cortisol into men aged 20–38 and healthy (screened) men and women aged 63–83 years and followed its disappearance from the circulation for 3 h. In all three groups the disappearance curves corresponded closely to a double exponential, with half-lives of around 5 and 65 min. A two-pool model was assumed, one being purely a side-pool. The initial and total volumes of distribution and the MCR, but not the clearance rate for exchange between the two pools, tended to be lower in the elderly men than in the young; only the difference in total volume was significant. All these parameters were lower in the elderly women than in the elderly men. We conclude that any decline in cortisol MCR and related kinetic parameters with aging in men is small compared with variation from other sources. These parameters are lower in elderly women than men, in line with a reported sex difference in MCR in young subjects.