Long-Term Effects of Bilateral Oophorectomy on Brain Aging: Unanswered Questions from the Mayo Clinic Cohort Study of Oophorectomy and Aging

Author:

Rocca Walter A1,Shuster Lynne T2,Grossardt Brandon R3,Maraganore Demetrius M4,Gostout Bobbie S5,Geda Yonas E6,Melton L Joseph7

Affiliation:

1. Walter A Rocca, Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA, Tel.: +1 507 284 3568, Fax: +1 507 284 1516,

2. Lynne T Shuster, Department of Internal Medicine, Women's Health Clinic, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA, Tel.: +1 507 538 6830, Fax: +1 507 266 3988,

3. Brandon R Grossardt, Division of Biomedical Statistics & Informatics, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA, Tel.: +1 507 284 5007, Fax: +1 507 284 9542,

4. Demetrius M Maraganore, Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA, Tel.: +1 507 284 3219, Fax: +1 507 284 3665,

5. Bobbie S Gostout, Division of Gynecologic Surgery, Department of Obstetrics & Gynecology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA, Tel.: +1 507 266 8701, Fax: +1 507 266 9300,

6. Yonas E Geda, Department of Psychiatry & Psychology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA, Tel.: +1 507 284 3789, Fax: +1 507 284 4158,

7. L Joseph Melton III, Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN, USA, Tel.: +1 507 284 5545, Fax: +1 507 284 1516,

Abstract

In the Mayo Clinic Cohort Study of Oophorectomy and Aging, women who had both ovaries removed before reaching natural menopause experienced a long-term increased risk of parkinsonism, cognitive impairment or dementia, and depressive and anxiety symptoms. Here, we discuss five possible mechanistic interpretations of the observed associations; first, the associations may be non-causal because they result from the confounding effect of genetic variants or of other risk factors; second, the associations may be mediated by an abrupt reduction in levels of circulating estrogen; third, the associations may be mediated by an abrupt reduction in levels of circulating progesterone or testosterone; fourth, the associations may be mediated by an increased release of gonadotropins by the pituitary gland; and fifth, genetic variants may modify the hormonal effects of bilateral oophorectomy through simple or more complex interactions. Results from other studies are cited as evidence for or against each possible mechanism. These putative causal mechanisms are probably intertwined, and their clarification is a research priority.

Publisher

SAGE Publications

Subject

General Medicine

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