A total of 45 healthy, well-educated women (most under 60 years of age), all of whom had initiated hormone therapy within 1 week of their last menstrual cycle, were involved in the study. All had baseline increased risks for Alzheimer disease: a personal history of depression, a first-degree relative with Alzheimer disease, or ApoE-e4 allele positivity. After baseline imaging with FDG-PET, participants were randomly assigned to either remain on their current hormone therapy or to stop it. Two years later, the 28 women who had remained on hormone therapy and the 17 who had stopped it were rescanned with PET imaging. Metabolic activity was significantly better preserved in the medial prefrontal cortex in women who remained on hormone therapy. Of interest, in the precuneus and posterior cingulate regions, metabolic activity was significantly reduced by discontinuation of estradiol and was extremely well preserved among women who stayed on estradiol. Staying on Premarin gave no such protection from degeneration of metabolic activity, and coupling synthetic progestin to either regimen made things worse. The investigators point out that these women were all cognitively intact throughout the study. They plan to repeat this study in a large sample of women without any risk factors for Alzheimer disease.