Sex hormones and cognitive function in older men

OBJECTIVES: Recent studies have suggested that estrogen may improve cognitive function or prevent cognitive decline in older women. Little research has been conducted on exogenous or endogenous sex hormones and cognition in older men, yet it has been hypothesized that testosterone, either directly or by conversion to estrogens, may improve cognitive function. We investigated whether serum level of testosterone and estradiol is associated with cognition in older community-dwelling men. DESIGN: A cross-sectional study. SETTING: Population-based listings in the Monongahela Valley near Pittsburgh, Pennsylvania. PARTICIPANTS: Three hundred ten men (mean age +/- standard deviation = 73.0 +/- 7.1) who were part of a cohort study. MEASUREMENTS: We measured cognitive function using the Mini-Mental State Examination (MMSE), Trails B, and Digit Symbol. Sex hormone levels were determined by radioimmunoassay from serum obtained at the time of cognitive testing and analyzed by tertile. RESULTS: No consistent association between total testosterone level and cognitive test scores was observed. However, men with high bioavailable (loosely protein-bound) testosterone had better cognitive test scores on all three tests (P less than or equal to .001). Total estradiol levels were associated with worse cognitive scores on Digit Symbol (P < .001) and Trails B (P = .002), but bioavailable estradiol levels were not associated with cognitive function. Level of sex hormone binding globulin (SHBG) was negatively associated with cognitive scores on all three tests (P less than or equal to .001). After adjusting for age and education, the statistical significance lessened for bioavailable testosterone (MMSE, P = .086; Digit Symbol, P = .047; Trails B, P = .076) and became nonsignificant for SHBG (all cognitive tests P > .10). CONCLUSIONS: Our findings support the hypothesis that higher levels of bioavailable testosterone, but not of bioavailable estradiol, are associated with better cognitive function in older men. In addition, bioavailable measures of testosterone may better reflect hormone levels available to the brain and thus be more closely associated with central nervous system outcomes such as cognition. Future studies, especially randomized trials, should be undertaken to determine whether testosterone may protect against cognitive decline in older men.