Impaired growth hormone response to sodium valproate in normal aging

Evidence has been provided for impaired neurotransmitter functioning in the brain of elderly subjects. In order to assess central GABAergic transmission, the activity of the hypothalamic GABA system may be investigated by basal growth hormone (GH) response to the GABAergic drug sodium valproate (SV). For this purpose 15 healthy men (aged 19-81 years) received orally 800 mg SV or placebo tablets on two different occasions, 1 week apart. Blood samples were collected before and after drug administration for determining GH and SV plasma levels. A clear-cut increase in plasma GH was observed following SV (P less than 0.001 in young persons, P less than 0.005 in old subjects), but in the aged subjects this rise was statistically lower than in the young men (P less than 0.001 at t = 90 min). No difference was observed in basal GH levels and in SV plasma concentrations between elderly and young subjects. delta GH (= maximum post-SV GH level minus baseline GH value) was significantly inversely related to age (r = -0.90, P less than 0.001). These results may suggest an impaired hypothalamic-pituitary responsiveness to a pharmacological challenge enhancing endogenous GABA tone in the elderly.