Abstract: Menopause is marked by a 90% decline in endogenous ovarian hormone production. Among brain regions affected by this reproductive aging event is the hippocampus (HC), which is responsible for encoding flexible and efficient spatial navigation. In rodents, estradiol’s influence on HC structure has been marked by changes in dendritic spine density and ultimately changes in behavior in spatial navigation (Korol et al., 2004). We aimed to bridge previous findings in animals to humans in the context of reproductive aging. We collected high resolution structural HC scans and collected blood samples from healthy midlife adults who were later tested on a behavioral Dual-solution Paradigm (DSP), a task testing for navigation strategy. For comparison, we also used our DSP to test navigation strategy in a cohort of healthy young adults. We hypothesized that reductions in estradiol levels in midlife women throughout reproductive aging would result in a decrease in HC volume, which would ultimately shift women’s strategies from using a flexible HC-mediated strategy to an alternatively-mediated rigid strategy in the DSP task when compared to younger adults. Results of this pilot study indicated no main effect of reproductive stage on hippocampal subfield morphology and a main effect of reproductive stage on spatial navigation strategy among our female cohort, indicating a shift away from flexible navigation to heavily relying on learned routes. By investigating the midlife period, further research could delineate how earlier reproductive aging, as opposed to later chronological aging, influences cognitive changes decades earlier in the aging process.