Sex hormones and cognitive decline in elderly men

https://doi.org/10.1016/j.psyneuen.2008.08.008Get rights and content

Summary

Decline of cognitive function with age may be due, in part, to hormonal changes and it has been hypothesized that higher levels of endogenous sex hormones preserve brain function. The aim of this prospective cohort study was to determine the relative contribution of endogenous sex hormones to cognitive decline in a population-based sample of 242 elderly men aged 73–91 at baseline. Endogenous sex hormone levels were measured at baseline and participants underwent a cognitive assessment at baseline and at follow-up after 4 years. Higher estradiol (total and bioavailable) and estrone levels were associated with an increased risk of cognitive decline in elderly men independent of age, cardiovascular risk factors, atherosclerosis, and APOE genotype. These findings do not support the hypotheses that higher levels of endogenous sex hormones preserve brain function.

Introduction

Decline in cognitive function is one of the major symptoms of dementia. The “preclinical phase” of detectable lowering of cognitive functioning precedes the appearance of dementia by many years (Park et al., 2003). Recently, sex hormones have been identified as factors that modulate risk for cognitive decline. The actions of testosterone and estradiol in the brain of older people are not well understood, but in vivo and in vitro experimental studies suggest these hormones may have multiple neuroprotective effects (Veiga et al., 2004).

In addition to the experimental data, the results of observational studies are contradictory (Muller et al., 2003). Several studies suggest that higher levels of endogenous estradiol or testosterone may preserve brain function (Barrett-Connor et al., 1999, Yaffe et al., 2000, Muller et al., 2005). More recently, however, adverse effects of estrogen on brain function in women have been demonstrated (Geerlings et al., 2003, Shumaker et al., 2003). And in recent prospective studies in men and women, higher levels of total and bioavailable estradiol were associated with an increased risk of cerebral small vessel disease, cognitive decline and Alzheimer’s disease (Geerlings et al., 2006, Irie et al., 2006, Ravaglia et al., 2007). Here, we examine the association of endogenous levels of sex hormones with cognitive decline in very old Caucasian men.

Section snippets

Subjects

In 1996, names and addresses of all male inhabitants >70 years of age were drawn from the municipal register of Zoetermeer, a medium-sized town in the Midwestern part of the Netherlands, and 1567 men were invited as described previously (Muller et al., 2004). A total of 886 men did not respond to the mailed invitation in which it was already mentioned that subjects who did not live independently or with severe mobility problems would not be allowed to participate. After exclusion of subjects

Results

Mean age of the population at baseline was 77.4 years (range, 73–91 years). Subjects in the study (N = 242) were significantly younger and had a higher MMSE at baseline than the subjects who dropped out (N = 161). No differences were found in baseline hormone levels, life style factors, and cardiovascular risk factors.

Descriptive values of the sex hormone levels and general characteristics at baseline according to total estradiol tertiles are presented in Table 1. Mean (S.D.) total estradiol level

Discussion

This population-based prospective study of 242 independently living elderly men showed that high serum levels of total and free estradiol and estrone are associated with an increased risk of cognitive decline independent of age, cardiovascular risk factors, and APOE-ɛ4. While no significant associations were found for various measures of circulating testosterone, the results are not compatible with a protective effect against cognitive decline.

The association between high endogenous estradiol

Role of the funding sources

No study sponsor(s) have been involved in this study.

Conflict of interest

The authors have nothing to disclose.

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