In addition to chronological aging, women undergo reproductive aging in midlife, during which they experience a depletion of ovarian hormones including estradiol. Estradiol is a master regulator of many neurological and physiological functions, including memory circuitry and metabolic function. With menopause, there is a 15-25% decrease in cerebral glucose metabolism resulting in a period of vulnerability in women that may increase susceptibility to neurodegeneration and cognitive impairment. Here, we assessed the longitudinal impact of metabolic health, in relation to sex and reproductive aging, on memory performance and cellular aging in early midlife. Women live a third of their life after menopause and thus, understanding the impact of ovarian decline on the brain is particularly important for women’s health. This work will inform in women, critical windows of vulnerability, mechanistic targets for intervention, identify early in life high-risk populations, and will highlight key differences with aged-matched men.