Male Sex Hormones and Systemic Inflammation in Alzheimer Disease

Several studies have shown that the levels of sex hormones in men with Alzheimer disease (AD) differ from men without AD. Therefore, male sex hormones have been postulated as risk modifiers in AD, possibly through immunomodulatory effects on known inflammatory AD risk factors, such as tumor necrosis factor alpha (TNF-alpha). We conducted a cross-sectional study of sex hormones and TNF-alpha levels in 94 community-dwelling men with AD. Comparisons were made with normal values derived from the literature. Men with AD had lower free testosterone levels than non-AD men (1-sample t test: age < 80, P = 0.0002; age >= 80, P < 0.0001), and higher luteinizing hormone (LH) levels (Wilcoxon signed rank test: age < 80, P = 0.001; age >= 80, P < 0.0001). Within the cohort of men with AD, there was a positive correlation between LH and TNF-alpha (Spearman r = 0.25, P = 0.019), and this remained significant after correcting for age (partial r = 0.21, P = 0.05). These data support the hypothesis that sex hormones and the immune system influence each other in AD. Furthermore, modulatory effects between LH and TNF-alpha may provide a mechanism for an effect of male sex hormones on AD risk.