INTRODUCTIONWomen with early bilateral salpingo-oophorectomy (BSO) have greater Alzheimer's disease (AD) risk than women with spontaneous menopause (SM), but the pathway toward this risk is understudied. Considering associative memory deficits may reflect early signs of AD, we studied how BSO affected brain activity underlying associative memory.METHODSEarly midlife women with BSO (with and without 17 beta-estradiol therapy [ET]) and age-matched controls (AMCs) with intact ovaries completed a face-name associative memory task during functional magnetic resonance imaging. Hippocampal activity along the anteroposterior axis during associative encoding and retrieval was compared among three groups (BSO [n = 28], BSO+ET [n = 35], AMCs [n = 40]).RESULTSBoth BSO groups (with and without ET) showed lower posterior hippocampal activation during encoding compared to the AMC group. However, this difference in activation was not significantly correlated with associative memory task performance.DISCUSSIONEarly 17 beta-estradiol loss may influence posterior hippocampal activity during associative encoding, possibly presaging late-life AD.Highlights After ovarian removal, changes in hippocampal function may affect dementia risk. Midlife ovarian removal is associated with less activation in the posterior hippocampus. Estradiol therapy may ameliorate alterations in brain function during learning.