Hysterectomy, oophorectomy, estrogen, and the risk of dementia

Background: The long-term cognitive effects of hysterectomy and oophorectomy remain controversial. Objective: To explore the association of hysterectomy and oophorectomy with the subsequent risk of cognitive impairment or dementia. Methods: We combined the results from two cohort studies graphically and conducted additional analyses. Results: Combined results from the Mayo Clinic Cohort Study of Oophorectomy and Aging and from a Danish nationwide cohort study suggest that the extent of gynecologic surgery may correlate with a stepwise increase in the risk of cognitive impairment or dementia. Compared with women with no gynecologic surgeries, the risk of cognitive impairment or dementia was increased in women who had hysterectomy alone, further increased in women who had hysterectomy with unilateral oophorectomy, and further increased in women who had hysterectomy with bilateral oophorectomy. The risk increased with younger age at the time of the surgery. Conclusion: We hypothesize that both hysterectomy and oophorectomy may have harmful brain effects via direct endocrinological mechanisms or other more complex mechanisms. Estrogen deficiency appears to play a key role in these associations, and estrogen therapy may partly offset the negative effects of the surgeries.