In comparison to men, women are twice as frequently affected by dementia. Hormonal sex differences might be one reason. There is a tremendous body of scientific evidence that estrogens are neurotrophic, neuroprotective, and psychoprotective. However, clinical trials investigating the effect of estrogens on cognition are controversial. This might be due to the time point (“window of opportunity”) and the neuronal health status (“healthy cell bias”), respectively, when estrogens are initiated. Therefore, primary hormonal prevention of cognitive decline might be possible, but secondary and tertiary prevention of dementia is not. However, until further research has revealed clear evidence that estrogens are effective in primary prevention the recommendations of the neurological society should be followed aiming to avoid intrinsic and extrinsic risk factors of dementia.