The Long-Term Effects of Oophorectomy on Cognitive and Motor Aging Are Age Dependent

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Abstract
Background: The evidence for a neuroprotective effect of estrogen in women remains controversial. Objective: We studied the long-term risk of parkinsonism and of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Methods: We conducted a historical cohort study among all women residing in Olmsted County, Minn., USA, who underwent unilateral or bilateral oophorectomy before the onset of menopause for a noncancer indication from 1950 through 1987. Each member of the oophorectomy cohort was matched by age to a referent woman from the same population who had not undergone oophorectomy. In total, we studied 1,252 women with unilateral oophorectomy, 1,075 women with bilateral oophorectomy, and 2,368 referent women. Women were followed for a median of 25–30 years. Parkinsonism was assessed using screening and examination, through a medical records- linkage system, and through death certificates. Cognitive status was assessed using a structured questionnaire via a direct or proxy telephone interview. Results: The risk of parkinsonism and of cognitive impairment or dementia increased following oophorectomy. In particular, we observed significant linear trends of increasing risk for either outcome with younger age at oophorectomy. Conclusion: Our findings, combined with previous laboratory and epidemiologic findings, suggest that estrogen may have an age-dependent neuroprotective effect.