Unraveling the Directional Link between Adiposity and Inflammation: A Bidirectional Mendelian Randomization Approach

Abstract

Main Outcome Measures: Measures of executive function, memory, and spatial cognition were obtained before and after treatment. Hormone levels were obtained 10 times over the course of the study. Results: Counter to expectations, hormone treatment did not affect cognition (ps 0.10). Free testosterone was positively related to spatial cognition in older men after treatment and controlling for age and estradiol level or exclusion of the hypogonadal men (P 0.02). Estradiol was negatively associated with working memory controlling for the same variables (P 0.01). Blinding to treatment assignment was maintained, with the exception of the hypogonadal group. Conclusions: A significant change in sex hormone status, including complete hypogonadism, does not modify cognition in men. These findings, along with studies that show a risk for neurodegenerative disease in those with low testosterone, suggest that sex hormone status may be important for neuroprotection in aging but not modulation of normal day-to-day cognitive function.