BACKGROUND: Although studies have demonstrated a correlation between sex hormone-related traits [such as sex hormone binding globulin (SHBG) and testosterone] and Alzheimer's Disease (AD), the link remains uncertain due to the intricacies of AD pathology. The study aimed to investigate the possible causal link between sex hormone-related traits and AD. METHODS: The authors collected data from extensive genome-wide association studies (GWASs) of European ancestry on sex hormone-related traits and AD. Univariate and multivariate Mendelian randomization (MR) analyses were conducted to explore the possible causal relationship between these traits and AD. We used inverse variance weighted (IVW) MR as the main analysis. RESULTS: The use of univariate MR-IVW revealed a possible causal relationship between SHBG [ORs (95% CI), 1.005 (1.001-1.009), CONCLUSION: Our study using the MR methodology indicates that increase of SHBG level and decrease of testosterone level in females are positively linked to an increased risk of developing AD. Importantly, testosterone plays a mediating role in the causal pathway from SHBG to females AD.