The relevance of estrogens for cognition in older women is still debated. In this double-blind experiment hysterectomized women (age 58-75 years) received placebo (n = 13), estradiol (n = 12) or estradiol/progesterone (n = 10) treatment. Cognitive testing (nine different tests) took place at baseline, after 4 and 24 weeks of treatment. Strong hormone increases occurred in both active treatment groups. However, no beneficial effects in any of the cognitive tests could be detected. This study, therefore, does not support the notion that treatment with sex hormones has beneficial effects on cognition in older hysterectomized women. The human brain might loose its responsiveness to gonadal steroids with aging or prolonged hormone depletion.