Cognition Is Not Modified by Large but Temporary Changes in Sex Hormones in Men

Abstract

Little is known about the role of testosterone and estradiol on cognition in healthy older men. The cognitive effects of increasing or lowering testosterone or estradiol were examined. Cognition was assessed before and after 6 wk of double-blind placebo-controlled hormone modification. The study was conducted at an academic medical center. Healthy older (ages 60-80 yr) and younger men (ages 25-35 yr) were recruited from the community. Men were randomized to one of four treatments: 1) maintain testosterone and estradiol at eugonadal levels for young men (GnRH agonist + testosterone gel); 2) block testosterone's conversion to estradiol (GnRH agonist + testosterone gel + aromatase inhibitor); 3) induce hypogonadism (GnRH agonist alone); and 4) all placebo. 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. Counter to expectations, hormone treatment did not affect cognition (P > 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. 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.