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This Article Figures Only Full Text Full Text (PDF) CME: Take the course for this article: Volume 69, Number 11, September 11, 2007 All Versions of this Article: 01.wnl.0000276984.19542.e6v1 69/11/1074    most recent Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rocca, W. A. Articles by Melton, L. J. Search for Related Content PubMed PubMed Citation Articles by Rocca, W. A. Articles by Melton, L. J., III Related Collections Endocrine All Cognitive Disorders/Dementia Cognitive aging Cohort studies Risk factors in epidemiology

Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause

From the Division of Epidemiology, Department of Health Sciences Research (W.A.R., L.J.M.), Department of Neurology (W.A.R., J.H.B., D.M.M., J.E.A.), and Division of Biostatistics, Department of Health Sciences Research (B.R.G., M. de A.), Mayo Clinic College of Medicine, Rochester, MN.

Address correspondence and reprint requests to Dr Rocca, Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN 55905 rocca{at}mayo.edu

Objective: There is increasing laboratory evidence for a neuroprotective effect of estrogen; however, the clinical and epidemiologic evidence remains limited and conflicting. We studied the association of oophorectomy performed before the onset of menopause with the risk of subsequent cognitive impairment or dementia.

Methods: We included all women who underwent unilateral or bilateral oophorectomy before the onset of menopause for a non-cancer indication while residing in Olmsted County, MN, 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 813 women with unilateral oophorectomy, 676 women with bilateral oophorectomy, and 1,472 referent women. Women were followed through death or end of study using either direct or proxy interviews.

Results: Women who underwent either unilateral or bilateral oophorectomy before the onset of menopause had an increased risk of cognitive impairment or dementia compared to referent women (hazard ratio [HR] = 1.46; 95% CI 1.13 to 1.90; adjusted for education, type of interview, and history of depression). The risk increased with younger age at oophorectomy (test for linear trend; adjusted p < 0.0001). These associations were similar regardless of the indication for the oophorectomy, and for women who underwent unilateral or bilateral oophorectomy considered separately.

Conclusions: Both unilateral and bilateral oophorectomy preceding the onset of menopause are associated with an increased risk of cognitive impairment or dementia. The effect is age-dependent and suggests a critical age window for neuroprotection.

Abbreviations: AD = Alzheimer disease; ADL = activities of daily living; HR = hazard ratio; TICS-m = Telephone Interview for Cognitive Status-modified; WHI = Women's Health Initiative.

Editorial, see page 1070

e-Pub ahead of print at www.neurology.org.

Funded by NIH grants R01 NS33978 from the National Institute of Neurological Disorders and Stroke and R01 AR30582 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Disclosure: The authors report no conflicts of interest.

Received January 22, 2007. Accepted in final form March 28, 2007.

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