Prospective measurements of dehydroepiandrosterone sulfate in a cohort of elderly subjects: Relationship to gender, subjective health, smoking habits, and 10-year mortality

Abstract

The decrease with age of the adrenal-secreted dehydroepiandrosterone sulfate (DHEAS) in serum has suggested that it may be causally related to longevity. For the PAQUID [People (Personnes) Aged (Agé es) About What (Quid, in Latin)] cohort of elderly subjects, we have previously reported higher DHEAS in men than in women, a decrease with age and, among men, a negative correlation between the DHEAS level and mortality at 2 and 4 years. Here, with an 8-year followup in 290 subjects, we show a global decrease of 2.3% per year for men and 3.9% per year for women. However, in approximately 30% of cases, there was an increase of DHEAS. We observed no relationship between the evolution of DHEAS level and functional, psychological, and mental status, possibly because of selection by death. In women, no association was found between mortality and DHEAS level. In men, the relative risk (RR) of death was higher for the lowest levels of DHEAS (RR ‫؍‬ 1.9, P ‫؍‬ 0.007), with RR ‫؍‬ 6.5, P ‫؍‬ 0.003 for those under 70 years old, a result indicating heterogeneity of the population. There was an effect of subjective health on mortality that disappeared after adjustment of DHEAS levels, suggesting its relation with these DHEAS levels. Death RR was much higher in smokers with a low DHEAS level than in nonsmokers with high DHEAS (RR ‫؍‬ 6.7, P ‫؍‬ 0.001). We submit that the involvement of DHEAS is possibly different according to gender, that association between low DHEAS level and mortality only for men under 70 years old possibly reflects heterogeneity of the population, and that DHEAS level is a reliable predictor of death in male smokers. I n human beings, dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are secreted adrenal steroids whose role is still poorly understood. Except in the nervous system, no receptor for those steroids has been described, and they likely operate in part by a transformation into androgens and estrogens (1-5) and probably also directly as neuroactive steroids (6). Furthermore, DHEAS concentration declines with age (7, 8) and remains 10-20% higher in men than in women (9), despite an important interindividual range.The decline of DHEAS concentrations with aging has led to the suggestion that DHEAS could play a role in itself and be implicated in longevity. Thus, DHEAS has been studied with controversial results in several processes that occur during aging (10, 11). In particular with reference to the mortality issue studied in this paper, we note that DHEAS has been inversely related to cardiovascular diseases in men (12-16), but this relation was not found in women (17).To clarify the role of DHEAS, our strategy within the PAQUID ʈ program (a prospective cohort study of elderly subjects from the southwest of France) was to relate DHEAS level with several health parameters and mortality. Among the 3,777 elderly subjects of this cohort, 622 volunteers agreed to have blood sampling after 1 year of followup. The measurement of DHEAS concentrations at this time allowed us to confirm the already known ...

Dehydroepiandrosterone, obesity and cardiovascular disease risk: a review of human studies

“…It has also been hypothesized that differences may be attributable to population variability. For example, the prospective study by Mazat et al (109), demonstrated that the relative risk of 8-year mortality associated with low DHEA-S was 3.4 times higher in males under 70 years compared with older men (odds ratios of 6.5 versus 1.9 respectively), suggesting substantial heterogeneity in this population according to age (109). Adjustment for BMI in most studies may have attenuated the relationship of DHEA-S to cardiovascular disease endpoints.…”

“…The studies performed in women (Table 4) are very consistent in demonstrating that there is no relationship between plasma DHEA-S levels and mortality from cardiovascular disease or other causes. Indeed, no significant association was found in all seven population studies performed to date (105)(106)(107)(108)(109)(110)(111)(112). A trend for higher mortality rates in women with elevated DHEA-S was found in the study by Barrett-Connor & Khaw Gruen (110).…”

“…Thus, the available studies on mortality rates and serum DHEA-S in men suggest that low DHEA-S values are associated with a moderate, though significant, increase in the relative risk of mortality (approximately 1.5-fold) (108,109,112).…”

A longitudinal study of dehydroepiandrosterone sulphate (DHEAS) change in older men and women: the Rancho Bernardo Study

“…This discrepancy remains largely unexplained. It could be due to the way that change is defined in each of the studies or to the influence of a regression to the mean phenomenon (8,9). Regression to the mean describes the tendency of high or low values of a biological marker to return towards the mean upon re-testing (10 -13).…”

Hormonal regulation of longevity in mammals

“…DHEA treatment of older men and women has not been convincingly demonstrated to have significant clinical benefits, with the exception of a study by Morales et al (1994) showing improvement in self-reported physical and psychological well-being in post-menopausal women. DHEA may be a reliable biomarker of aging specifically in men (Roth et al, 2002) and a potential predictor of mortality (Mazat et al, 2001). Hornsby (1997) makes the case that the most likely function for DHEA is as a precursor for conversion to potent androgens, which mediate adrenarchy, a sexual signaling mechanism occurring just before puberty in higher primates.…”