Hysterectomy, Oophorectomy, Estrogen, and the Risk of Dementia
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Background: The long-term cognitive effects of hysterectomy and oophorectomy remain controversial. Objective: To explore the association of hysterectomy and oophorectomy with the subsequent risk of cognitive impairment or dementia. Methods: We combined the results from two cohort studies graphically and conducted additional analyses. Results: Combined results from the Mayo Clinic Cohort Study of Oophorectomy and Aging and from a Danish nationwide cohort study suggest that the extent of gynecologic surgery may correlate with a stepwise increase in the risk of cognitive impairment or dementia. Compared with women with no gynecologic surgeries, the risk of cognitive impairment or dementia was increased in women who had hysterectomy alone, further increased in women who had hysterectomy with unilateral oophorectomy, and further increased in women who had hysterectomy with bilateral oophorectomy. The risk increased with younger age at the time of the surgery. Conclusion: We hypothesize that both hysterectomy and oophorectomy may have harmful brain effects via direct endocrinological mechanisms or other more complex mechanisms. Estrogen deficiency appears to play a key role in these associations, and estrogen therapy may partly offset the negative effects of the surgeries.
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For those without contraindications who undergo RRSO before age 45, estradiol must be initiated soon after surgery to obtain optimal protection against cognitive concerns.
“Moreover, for those without contraindications who undergo RRSO before age 45, estradiol must be initiated soon after surgery to obtain the optimal protection against cognitive concerns, and studies indicate that estradiol therapy is only partially protective against several domains of cognitive decline [2,4,12,13].”
From Treating new-onset cognitive complaints after risk-reducing salpingo-oophorectomy: A randomized controlled crossover trial of lisdexamfetamine (2024) · cites this paper as [13]
The Mayo Clinic Cohort Study section reports that estrogen therapy after premenopausal bilateral oophorectomy partly offset the increased risk of cognitive impairment or dementia. The Interpretation of Combined Findings section reports no increased risk among women treated with estrogen until at least age 50 and conditionally recommends hormone therapy after surgery before natural menopause. It does not establish a requirement to initiate estradiol soon after RRSO, an age-45 cutoff, or that this timing provides optimal protection. (LLM, conf=0.88)
Experimental — accuracy not yet measuredEstradiol therapy is only partially protective against several domains of cognitive decline.
“Moreover, for those without contraindications who undergo RRSO before age 45, estradiol must be initiated soon after surgery to obtain the optimal protection against cognitive concerns, and studies indicate that estradiol therapy is only partially protective against several domains of cognitive decline [2,4,12,13].”
From Treating new-onset cognitive complaints after risk-reducing salpingo-oophorectomy: A randomized controlled crossover trial of lisdexamfetamine (2024) · cites this paper as [13]
The Abstract Conclusion says estrogen therapy may partly offset the negative effects of hysterectomy and oophorectomy, and the Mayo Clinic Cohort Study section says it partly offset the risk of cognitive impairment or dementia after oophorectomy. The paper does not establish partial protection by estradiol specifically across several distinct domains of cognitive decline; its reported outcome is cognitive impairment or dementia. (LLM, conf=0.88)
Experimental — accuracy not yet measuredClinical longitudinal studies have shown susceptibility of women with surgical menopause at young ages to cognitive decline and dementia.
“Yet, clinical longitudinal studies have shown susceptibility of women with surgical menopause at young ages to cognitive decline [14] and dementia [52].”
From Sex differences in Alzheimer’s disease and common neuropathologies of aging (2018) · cites this paper as [52]
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- Authors
- Rocca, W. A., Grossardt, B. R., Shuster, L. T., & Stewart, E. A.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Rocca, Walter A.
- Venue
- Neurodegenerative Diseases
- Publisher
- S. Karger AG
- Published
- 2012
- Volume
- 10
- Issue
- 1-4
- Pages
- 175-178
- ISSN
- 1660-2854 (ISSN-L)
- 1660-2862
- PMC
- PMC3702015
- OpenAlex
- W2090316207
- Cited by
- 122
- References
- 10
- Citations by year
- 2026: 13 · 2025: 8 · 2024: 11 · 2023: 20 · 2022: 9 · 2021: 9 · 2020: 5 · 2019: 12 · 2018: 8 · 2017: 2 · 2016: 10 · 2015: 6 · 2014: 3 · 2013: 5 · 2012: 1
- FWCI
- 3.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurodegenerative Diseases (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG034676, AG-034676)
- National Institute of Neurological Disorders and Stroke (NS 033978, R01NS033978)
- National Center for Research Resources (RR-024150, UL1RR024150)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (RC1HD063312, R01HD060503)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- hysterectomy, oophorectomy, dementia risk, cognitive impairment, estrogen deficiency, estrogen therapy, gynecologic surgery, menopause, age at surgery
- MeSH terms
- Adult, Aging, Cognition Disorders, Dementia, Estrogens, Female, Humans, Hysterectomy, Middle Aged, Ovariectomy, Risk Factors, Cohort Studies, Multicenter Studies as Topic, Young Adult
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