Higher serum free testosterone is associated with better cognitive function in older men, while total testosterone is not. The health in men study

Abstract

Objective: To determine the relationship of total and free serum testosterone to cognitive performance in older men. Design: Cross-sectional study of a population-based sample. Participants: A total of 2932 men aged 70–89 years. Measurements: Cognitive function was assessed using the Standardized Mini-Mental State Examination (SMMSE). Early morning sera were assayed for total testosterone, SHBG and LH. Free testosterone was calculated using the Vermeulen method. Results: There were weak positive correlations between SMMSE score and serum free testosterone (Spearman's rho = 0·06, P = 0·001) and total testosterone (r = 0·04, P = 0·027), and a weak negative correlation with LH (r = −0·07, P < 0·001). Men with SMMSE scores in the top quintile had higher serum free testosterone compared with those in the lowest quintile [median (interquartile range, IQR): 278 (228–335) vs. 262 (212–320) pmol/l, P = 0·003], but similar total testosterone [15·2 (11·9–18·8) vs. 14·8 (11·6–18·3) nmol/l, P = 0·118]. Increasing age, non-English-speaking background, lower educational attainment, presence of clinically significant depressive symptoms, and cardiovascular morbidity were associated with the lowest cognitive performance quintile. After their effects were taken into account in a multivariate analysis, serum free testosterone ≥ 210 pmol/l was associated with reduced likelihood of poor cognitive performance on the SMMSE [odds ratio (OR) 0·71, 95% confidence interval (CI) 0·52–0·97]. Conclusions: In community-dwelling older men, serum free testosterone ≥ 210 pmol/l is associated with better cognitive performance. In this context, calculated free testosterone seems to be a more informative measure of androgen status than total testosterone. Studies examining the contribution of androgens to age-related cognitive decline should incorporate an assessment of free testosterone concentration.