Abstract
Dehydroepiandrosterone (DHEA) and its sulphonated metabolite DHEAS are the major secretory products of the human adrenal gland. Despite the abundancy of these steroids in the circulation the precise function is uncertain. It has been postulated that they may be involved in the maturing and aging processes in man. An intriguing inverse relation has been described between DHEAS and cardiovascular mortality in men. In women from the same population this was not the case and in fact mortality due to cardiovascular disease was highest in women with the highest levels of DHEAS. Another interesting association is reported between DHEA and DHEAS and the enhancement of memory retention in mice. Reduced plasma concentration of DHEAS have been described in patients with Alzheimer's disease compared with age-matched controls. In the framework of a gerontologic study concerning all 1259 inhabitants aged 85 years and over of the Dutch community of Leiden (population +/- 105,000), DHEAS levels were determined in 138 subjects of this cohort. Of these, 53 were healthy subjects, selected from the population according to the health criteria of the SENIEUR protocol, which is based on clinical, pharmacological and laboratory data. This enabled us to assess reference values for this age group. Additionally DHEAS levels were measured in 64 young controls, 20-40 years of age, who also fulfilled these criteria. Reference values for the oldest old, derived from the healthy group, are 1.7 +/- 1.4 mumol/l for women and 2.2 +/- 1.1 mumol/l for men. DHEAS levels decreased fourfold between the young adults and those aged 85 and over. In men this decrease continued after the age of 85. DHEAS values tended to be higher in men than in women, both in the elderly, in all subgroups of elderly subjects, and in the young control group, but this sex-difference did not reach statistical significance. No difference was found between the DHEAS levels in subgroups according to the health status, the survival rate or the diagnosis of probable Alzheimer's disease. Many uncertainties concerning the role of DHEAS in the neuro-immuno-endocrinological network have yet to be unravelled and the question remains whether the age-related decrease of DHEAS is related to organ-specific failure on the level of the adrenals or the gonads, or whether it is a result of changes in feedback or regulatory mechanisms. DHEAS is one of the few compounds that shows a gradual decrease with advancing age, reaching an asymptotic low at the age of the maximum recorded life span.(ABSTRACT TRUNCATED AT 400 WORDS)
Published Version
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