Sex-Specific Effects of Endocrine Disruption on Aging and Alzheimer's Disease (SEED-AD) Research Program

Among women who undergo hysterectomy, many have their ovaries removed at the same time to help prevent cancer. Although fewer women are choosing to have this surgery done today compared with past decades, researchers estimate that currently, 1 in 8 women in the United States have had their ovaries removed before reaching natural menopause.

Women's health experts express increasing concern that removing the ovaries before natural menopause may have damaging long-term effects. Recent data indicate that this surgery may speed up harmful processes, including reduced physical and cognitive function. The surgery also may increase the risk of Alzheimer's disease.

To better understand these risks, experts in the Women's Health Research Center at Mayo Clinic has created the Sex-Specific Effects of Endocrine Disruption on Aging and Alzheimer's Disease (SEED-AD) Research Program. SEED-AD uses brain imaging biomarkers to study how abrupt hormonal disruption caused by removal of the ovaries affects women's long-term risk of cognitive decline and dementia. The program aims to provide critical insights to guide decision-making both for women considering premenopausal removal of their ovaries and for the healthcare professionals providing their care. This guidance is intended for patients with nonmalignant indications who are not at high genetic risk of ovarian cancer.

The SEED-AD program is conducting the Mayo Clinic Cohort Study of Oophorectomy and Aging-2 (MOA-2) to advance understanding of these questions and to develop the intended guidelines. The cohort includes 274 women who had their ovaries removed before reaching natural menopause and 214 who did not. All participants are from the Olmsted County, Minnesota, population. Participants are invited to a follow-up visit approximately 7 years after their initial visit. In addition, the study is recruiting 50 women with a history of premenopausal removal of ovaries, and 50 without, who have been followed through the Alzheimer's Disease Research Center at Mayo Clinic in Florida.

SEED-AD is funded by the National Institutes of Health.

Faculty

Kejal Kantarci, M.D., from the Mayo Clinic Department of Radiology, and Walter A. Rocca, M.D., M.P.H., from the Department of Quantitative Health Sciences, lead the SEED-AD Research Program. The research team includes investigators from Mayo Clinic campuses in both Rochester, Minnesota, and Jacksonville, Florida.

Kent R. Bailey, Ph.D.
Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences
Mayo Clinic in Minnesota

Gregg S. Day, M.D.
Department of Neurology
Mayo Clinic in Florida

Julie A. Fields, Ph.D., L.P.
Department of Psychiatry and Psychology
Mayo Clinic in Minnesota

Neill R. Graff-Radford, M.D.
Department of Neurology
Mayo Clinic in Florida

Ekta Kapoor, M.B.B.S.
Division of General Internal Medicine, Department of Internal Medicine
Mayo Clinic in Minnesota

Firat Kara, Ph.D.
Department of Radiology
Mayo Clinic in Minnesota

Val Lowe, M.D.
Department of Radiology
Mayo Clinic in Minnesota

John A. Lucas, Ph.D.
Department of Psychiatry and Psychology
Mayo Clinic in Florida

Chrisandra L. Shufelt, M.D.
Division of General Internal Medicine, Department of Internal Medicine
Mayo Clinic in Florida

Publications

Selected publications representing salient research findings related to SEED-AD are available below. You also can review full publications lists from Dr. Kantarci and Dr. Rocca, or search Mayo Clinic research publications for related topics.

Aversa Z, Frank RD, Geske JR, White TA, Heeren AA, Kapoor E, Rocca WA, Schafer MJ, Fields JA, Kantarci K, Mielke MM, LeBrasseur NK. Associations of biomarkers of cellular senescence with physical and cognitive function among older women with or without a history of premenopausal bilateral oophorectomy. Maturitas. 2025.

Jahanian O, Winham SJ, Kapoor E, Rocca WA, LeBrasseur N, Kantarci K, Morrow M, Mielke MM, Fortune E. Habitual physical activity and sedentary behavior among women with and without premenopausal bilateral oophorectomy: An exploratory study. Menopause. 2025.

Kantarci K, Kapoor E, Geske JR, Castillo A, Fields JA, Kara F, Knyazhanskaya EE, Schwarz CG, Senjem ML, Bailey KR, Lowe V, LeBrasseur NK, Rocca WA, Mielke MM. Premenopausal bilateral oophorectomy and Alzheimer's disease imaging biomarkers later in life. Alzheimer's & Dementia. 2025.

Rocca WA, Gazzuola Rocca L, Smith CY, Esterov D, Kapoor E, Geske JR, Bailey KR, Mielke MM, Kantarci K. Assessment of adverse childhood experiences in women: A study of reliability and predictive validity of self-reporting versus medical records abstraction in an American population. BMJ Open. 2025.

Rocca WA, Gazzuola Rocca L, Smith CY, Esterov D, Kapoor E, St. Sauver JL, Stewart EA, Kantarci K. Adverse childhood experiences increase the long-term accumulation of morbidity in women. Communications Medicine. 2025.

Zeydan B, Kantarci K. Influence of age and sex on presymptomatic phases of neurodegenerative diseases: Focus on multiple sclerosis and Alzheimer's disease. Revue Neurologique. 2025.

Mielke MM, Frank RD, Christenson LR, Reid RI, Fields JA, Knyazhanskaya ZE, Kara F, Vemuri P, Rocca WA, Kantarci K. Premenopausal bilateral oophorectomy and brain white matter brain integrity in later-life. Alzheimer's & Dementia. 2024.

Mielke MM, Kapoor E, Geske JR, Fields JA, LeBrasseur NK, Morrow MM, Winham SJ, Faubion LL, Castillo AM, Hofrenning EI, Bailey KR, Rocca WA, Kantarci K. Long-term effects of premenopausal bilateral oophorectomy with or without hysterectomy on physical aging and chronic medical conditions. Menopause. 2023.

Zeydan B, Tosakulwong N, Schwarz CG, Senjem ML, Gunter JL, Reid RI, Gazzuola Rocca L, Lesnick TG, Smith CY, Bailey KR, Lowe VJ, Roberts RO, Jack CR Jr, Petersen RC, Miller VM, Mielke MM, Rocca WA, Kantarci K. Association of bilateral salpingo-oophorectomy before menopause onset with medial temporal lobe neurodegeneration. JAMA Neurology. 2019.

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