Our estimates suggest that, for the older Taiwanese population, DHEAS is related to subsequent declines in various
dimensions of men's (but not women's) psychological and physical health. These findings differ from those in a previous cross-sectional
analysis based on the Taiwan study that found larger associations between DHEAS and mobility limitations and cognitive function for women than for men (Glei et al., 2004
). Although the present analysis uses the same measures of DHEAS as the earlier study, health outcomes in the earlier study were assessed at roughly the same time as the biological measures.
If DHEAS is related to survival, as some previous studies suggest, then mortality attrition may have biased our results. To explore this possibility, we recoded each health outcome variable as binary, where the value one indicates poor health or deceased by 2003. Then, we estimated two sets of logit models (with the same covariates as Model 2): one that included and one that excluded the 72 respondents who died between 2000 and 2003. The inclusion of deceased respondents had virtually no effect on the results (data not shown), suggesting that mortality attrition does not explain the inconsistencies between the cross-sectional and the longitudinal results.
Another possible explanation relates to sex differences in the extent to which a correlation between DHEAS and health results from reverse causality (that is, from the impact of disease on levels of DHEAS). Although there is some evidence that DHEA(S) levels decrease during illness (Herbert, 1995
; Kiechl et al., 2000
), there are few insights into how or whether this process differs by sex. Numerous correlation analyses relating health status to measures of DHEAS for men and women shed little light on the issue, both because the time sequence of cause and effect is unclear and because the patterns by sex vary enormously across studies. For example, Berr et al. (1996)
found that measures of functional and psychological status had stronger associations with levels of DHEAS in women, whereas Tilvis et al. (1999)
identified stronger associations between various diseases and levels of DHEAS in men. We used data from the earlier rounds of the Taiwan survey to examine the effects of changes in health during 1999–2000 and 1996–2000 on levels of DHEAS in 2000 and found evidence that an increase in mobility limitations over these periods was associated with lower levels of DHEAS for women but not men - a finding that is consistent with the stronger (but spurious) DHEAS associations identified for women in the cross-sectional analysis (Glei et al., 2004
These findings underscore the importance of using prospective rather than cross-sectional data to examine the effects of DHEAS on health. In , we summarize the few prospective studies that examine all-cause mortality or one of the four broad health outcomes explored in this paper. Note that the length of follow-up varies substantially across these studies—from one year in (Birkenhager-Gillesse et al., 1994
) to 19 years in
(Barrett-Connor and Goodman-Gruen, 1995
The studies, most of which examine survival or cognitive impairment, offer mixed evidence on the protective effects of DHEAS on men's health. Findings for women are more clear-cut: most studies find no significant effect, although one study (Yaffe et al., 1998
) suggests that lower levels of DHEAS are related to depression, and another study (Cappola et al., 2006
) finds that both low and high values of DHEAS are associated with increased mortality. Several review articles on sex differences in the effects of DHEA(S) on fatal and nonfatal cardiovascular outcomes (Khaw, 1996
; Porsova-Dutoit et al., 2000
; Thijs et al., 2003
) also indicate that DHEAS is associated with health outcomes more frequently for men than for women. Except for SEBAS, all of the studies listed in are based on Western populations. Thus, it is not clear whether differences in results between the Taiwanese and the Western samples represent true variation in the relationship between DHEAS and health across different social contexts or whether they result from other factors that vary across studies (e.g., sample selection, length of follow-up).
Summary of results from longitudinal studies with population-based samples regarding the relationship between DHEAS and health or survival
The evidence to date suggests that endogenous DHEAS is related to health outcomes for men, but not women, in both Western and non-Western populations. Numerous researchers have speculated that the apparent sex differences may result from differences between men and women in health-related behaviors (e.g., smoking or drinking) or cardiovascular risk factors (Barrett-Connor et al., 1986
; Mazat et al., 2001
). However, we find no evidence to support these hypotheses. Thus, we are left with vague explanations, similar to those proposed by others, pertaining to potential sex differences in DHEAS concentration and excretion rates, as well as differences between men and women in hormonal metabolism and sex steroid environments (Mazat et al., 2001
; Nafziger et al., 1991
; Ravaglia et al., 1996
; Trivedi and Khaw, 2001
Limitations of the present study include the shortness of the follow-up period and reliance on serum DHEAS measured at one point in time. The latter issue is of particular concern because concentrations of DHEAS differ from those of DHEA and because measured concentrations of DHEA(S) are likely to depend on the type of assay and vary over time (Nafziger et al., 1991
; Yaffe et al., 1998
). Future waves of SEBAS will provide a second measurement of DHEAS in 2006–2007, additional biomarkers, and information pertaining to health and survival in subsequent years. These data will permit more sophisticated analyses that distinguish between the effects of DHEAS on changes in health and those of illness on changes in DHEAS over a longer time interval. Despite the potential advantages of this type of study, more in-depth biomedical analysis will be required to enhance our understanding of the marked reductions in adrenal secretion of DHEA(S) with advancing age, the mechanisms that result in such a broad range of physiological effects, and how and why these effects differ between men and women.