The long-term effects of oophorectomy on cognitive and motor aging are age dependent

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.

Fig. 1.

Overall design of the Mayo Clinic Cohort Study of Oophorectomy and Aging. The numbers of women included in the follow-up were different for parkinsonism and for cognitive impairment or dementia. The numbers for cognitive impairment or dementia were reduced because only the women who were interviewed were informative. The asterisk indicates that a total of 95 referent women underwent oophorectomy after the index year and from 1950 through 1987. Because these women were included in both cohorts, they were counted only in the oophorectomy cohort regarding vital status at follow-up (2001–006).

Fig. 2.

Risk of parkinsonism by age at oophorectomy (unilateral or bilateral). A test for linear trend in log HRs was significant (p = 0.01). The test for trend included referent women who were assumed to have reached natural menopause around a median age of 50 years (HR = 1.00).

Fig. 3.

Risk of cognitive impairment or dementia by age at oophorectomy (unilateral or bilateral). A test for linear trend in the log HRs was significant (p < 0.0001). The test for trend included referent women who were assumed to have reached natural menopause around a median age of 50 years (HR = 1.00).