Objective: We used positron emission tomography to evaluate cerebral glucose metabolic change in postmenopausal women in a naturalistic observational study. Method: Women estrogen users (n=11) and non-users (n=9) were studied at baseline and 2 years later. Analyses focused on glucose metabolism in regions previously reported to decline in older persons at risk for Alzheimer’s disease (AD) (posterior cingulate and lateral temporal cortex). Results: Region of interest (ROI) analysis at baseline showed no regional differences between women estrogen users and non users. ROI follow-up analysis revealed that women non-users declined significantly in the posterior cingulate cortex (P=0.04). Statistical parametric mapping (SPM) analysis confirmed a significant decrease in metabolism of the posterior cingulate cortex among non-users at 2-year follow-up (P=0.004). In contrast, women estrogen users did not exhibit significant metabolic change in the posterior cingulate. Conclusions: Estrogen use may preserve regional cerebral metabolism and protect against metabolic decline in postmenopausal women, especially in posterior cingulate cortex, the region of the brain found to decline in the earliest stages of AD.