The Interplay Between Oophorectomy and Alzheimer's Disease: A Narrative Review

Alzheimer's disease (AD) is the leading cause of dementia worldwide and affects women more frequently than men. Although age remains the main risk factor, reproductive aging and changes in ovarian hormone exposure may also contribute to this difference. Premenopausal bilateral oophorectomy causes an abrupt loss of ovarian hormones, including estradiol, progesterone, and testosterone, and several observational studies have associated this change with a higher risk of later cognitive impairment or dementia, particularly when surgery is performed at a younger age. However, these studies have assessed different outcomes, including dementia, mild cognitive impairment, subjective cognitive changes, and AD-related imaging findings, and current evidence does not establish a direct causal relationship between oophorectomy and AD. Possible biological pathways include neuroinflammation, synaptic dysfunction, amyloid-β and tau-related changes, and cerebrovascular dysfunction, although much of the mechanistic evidence remains experimental or indirect. Genetic background, vascular health, age at surgery, and the duration of hormone deprivation may further influence individual risk. Hormone replacement therapy has an established role in the management of premature or early surgical menopause when there is no contraindication, but its effect on long-term AD prevention remains uncertain; the timing of treatment may be important, but current evidence does not confirm a preventive effect. This review summarizes current epidemiological, neuroimaging, and experimental evidence linking oophorectomy with cognitive health and AD, and discusses hormone therapy, pharmacological and non-pharmacological management, emerging research approaches, and remaining knowledge gaps. Future studies with detailed information on surgical timing, hormone exposure, genetic risk, vascular factors, longitudinal cognition, and AD-related biomarkers are needed to better define which women may be most vulnerable after premenopausal oophorectomy.