Abstract Introduction 17β-estradiol loss is related to Alzheimer’s disease (AD) risk factors, including disordered sleep and associative memory decrements. Women have higher risk for AD than men, and those with mid-life 17β-estradiol loss due to surgical menopause, including bilateral salpingo-oophorectomy (BSO) before age 48, have even higher risk. We wondered whether sleep and associative memory in women with BSO (mean age 44–46) would be comparable to those with spontaneous/natural menopause (SM; mean age 57), and whether 17β-estradiol-based hormone therapy (ET) might mitigate these effects. Methods We assessed sleep using the average of three nights of portable polysomnography (Temec) in women with BSO either taking ET (BSO+ET; n=16), or not (BSO; n=18), and in older spontaneously menopausal women (SM; n=14). Using EEG (Fp1-Fp2), we obtained sleep staging automatically (Neurobit Technologies). Participants also completed a face-name associative memory task during functional magnetic resonance imaging. Recognition accuracy and brain activation during encoding were measured. Results BSO exhibited reduced sleep efficiency compared to BSO+ET. For BSO, there was no relationship between percent of total sleep time in N3 and hippocampal activation during associative encoding, even though percent of total sleep time in N3 was negatively associated with hippocampal activation during associative encoding in BSO+ET. For all groups, including BSO, lower latency to consolidated N3 correlated with better associative memory accuracy. There were no group differences in associative memory accuracy. In contrast to BSO, SM showed significantly longer latency to consolidated N3 than BSO+ET. Conclusion Younger women with BSO have comparable sleep to older women in SM. In younger women with BSO, ET improves sleep efficiency. Further, while associative memory may be disrupted by increased latency to consolidated N3 in all women, BSO and BSO+ET showed similar associative memory accuracy and latency to consolidated N3. Only BSO+ET exhibited a significant correlation between hippocampal activity during associative encoding and time spent in N3, indicating that ET may support the negative relationship between N3 and hippocampal function. Overall, ET in younger women with BSO potentially ameliorates poor sleep and associative memory decrements. Support (if any) Alzheimer’s Association/Brain Canada Foundation: AARF-17-504715; Wilfred and Joyce Posluns Chair in Women’s Brain Health and Aging