Early midlife ovarian removal is associated with lower posterior hippocampal function

Alana Brown¹, Laura Gravelsins¹, Nicole J Gervais^{1

2}, Jenny Rieck³, Sophia Zhao¹, Annie Duchesne^{4

5}, Suzanne T Witt^{6

7}, Robin Kämpe^{6

8

9}, Rosanna Olsen^{1

3}, Morgan Barense¹, Elisabet Classon^{10

11}, Elvar Theodorsson^{9

12}, Jan Ernerudh^{9

13}, Elisabeth Åvall-Lundqvist^{9

14}, Preben Kjølhede^{9

15}, Maria Engström^{6

11}, Zhuo Shao^{16

17}, Marcus Bernardini¹⁸, Michelle Jacobson¹⁹, M Natasha Rajah²⁰, Cheryl Grady^{1

3

21}, Gillian Einstein^{1

3

22}

Affiliations

¹ Department of Psychology, University of Toronto, Toronto, Ontario, Canada.
² Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, the Netherlands.
³ Baycrest Academy of Research and Education, Baycrest Health Sciences, Toronto, Ontario, Canada.
⁴ Department of Psychology, Université du Québec à Trois-Rivières, Québec, Canada.
⁵ Department of Psychology, University of Northern British Columbia, Prince George, British Columbia, Canada.
⁶ Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden.
⁷ BrainsCAN, University of Western Ontario, London, Ontario, Canada.
⁸ Center for Social and Affective Neuroscience, Linköping University, Linköping, Sweden.
⁹ Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
¹⁰ Department of Acute Internal Medicine and Geriatrics, Linköping University, Linköping, Sweden.
¹¹ Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
¹² Division of Clinical Chemistry and Pharmacology, Linköping University, Linköping, Sweden.
¹³ Department of Clinical Immunology and Transfusion Medicine, Linköping University, Linköping, Sweden.
¹⁴ Department of Oncology, Linköping University, Linköping, Sweden.
¹⁵ Department of Obstetrics and Gynecology, Linköping University, Linköping, Sweden.
¹⁶ Genetics Program, North York General Hospital, Toronto, Ontario, Canada.
¹⁷ Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
¹⁸ Division of Gynecologic Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada.
¹⁹ Department of Gynecology, Women's College Hospital, Toronto, Ontario, Canada.
²⁰ Department of Psychology, Toronto Metropolitan University, Toronto, Ontario, Canada.
²¹ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
²² Tema Genus, Linköping University, Linköping, Sweden.

PMID: 39732509
PMCID: PMC11851323
DOI: 10.1002/alz.14447

Early midlife ovarian removal is associated with lower posterior hippocampal function

Alana Brown et al. Alzheimers Dement. 2025 Feb.

. 2025 Feb;21(2):e14447.

doi: 10.1002/alz.14447. Epub 2024 Dec 28.

Authors

Affiliations

¹ Department of Psychology, University of Toronto, Toronto, Ontario, Canada.
² Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, the Netherlands.
³ Baycrest Academy of Research and Education, Baycrest Health Sciences, Toronto, Ontario, Canada.
⁴ Department of Psychology, Université du Québec à Trois-Rivières, Québec, Canada.
⁵ Department of Psychology, University of Northern British Columbia, Prince George, British Columbia, Canada.
⁶ Center for Medical Image Science and Visualization, Linköping University, Linköping, Sweden.
⁷ BrainsCAN, University of Western Ontario, London, Ontario, Canada.
⁸ Center for Social and Affective Neuroscience, Linköping University, Linköping, Sweden.
⁹ Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
¹⁰ Department of Acute Internal Medicine and Geriatrics, Linköping University, Linköping, Sweden.
¹¹ Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
¹² Division of Clinical Chemistry and Pharmacology, Linköping University, Linköping, Sweden.
¹³ Department of Clinical Immunology and Transfusion Medicine, Linköping University, Linköping, Sweden.
¹⁴ Department of Oncology, Linköping University, Linköping, Sweden.
¹⁵ Department of Obstetrics and Gynecology, Linköping University, Linköping, Sweden.
¹⁶ Genetics Program, North York General Hospital, Toronto, Ontario, Canada.
¹⁷ Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
¹⁸ Division of Gynecologic Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada.
¹⁹ Department of Gynecology, Women's College Hospital, Toronto, Ontario, Canada.
²⁰ Department of Psychology, Toronto Metropolitan University, Toronto, Ontario, Canada.
²¹ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
²² Tema Genus, Linköping University, Linköping, Sweden.

PMID: 39732509
PMCID: PMC11851323
DOI: 10.1002/alz.14447

Abstract

Introduction: Women with early bilateral salpingo-oophorectomy (BSO) have greater Alzheimer's disease (AD) risk than women with spontaneous menopause (SM), but the pathway toward this risk is understudied. Considering associative memory deficits may reflect early signs of AD, we studied how BSO affected brain activity underlying associative memory.

Methods: Early midlife women with BSO (with and without 17β-estradiol therapy [ET]) and age-matched controls (AMCs) with intact ovaries completed a face-name associative memory task during functional magnetic resonance imaging. Hippocampal activity along the anteroposterior axis during associative encoding and retrieval was compared among three groups (BSO [n = 28], BSO+ET [n = 35], AMCs [n = 40]).

Results: Both BSO groups (with and without ET) showed lower posterior hippocampal activation during encoding compared to the AMC group. However, this difference in activation was not significantly correlated with associative memory task performance.

Discussion: Early 17β-estradiol loss may influence posterior hippocampal activity during associative encoding, possibly presaging late-life AD.

Highlights: After ovarian removal, changes in hippocampal function may affect dementia risk. Midlife ovarian removal is associated with less activation in the posterior hippocampus. Estradiol therapy may ameliorate alterations in brain function during learning.

Keywords: estradiol; functional magnetic resonance imaging; hippocampus; hormone therapy; menopause; oophorectomy.

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Conflict of interest statement

The authors have no financial or non‐financial interests to disclose. Author disclosures are available in the supporting information.

Figures

**FIGURE 1**
Face–name task design. A, Task includes 23 retrieval, 15 novel encoding, and 8 repeat encoding trials per run. Each circled number represents a different face‐name pair trial. B, Outline of task timing and conditions.

**FIGURE 2**
Locations of anatomical hippocampal ROIs. ROIs are shown in Montreal Neurological Institute space presented from coronal and sagittal views. A, anterior; Blue, posterior; L, left; P, posterior; Red, anterior; ROIs, regions of interest.

**FIGURE 3**
Effect of group on region‐of‐interest mean novel > repeat encoding contrast estimates for anterior and posterior hippocampus. Values are Winsorized; error bars represent standard error of the mean; * = P < 0.05 (FDR‐corrected). AMC, age‐matched control; BSO, bilateral salpingo‐oophorectomy; BSO+ET, bilateral salpingo‐oophorectomy with current use of 17β‐estradiol therapy (with or without progestogens).

See this image and copyright information in PMC

References

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Early midlife ovarian removal is associated with lower posterior hippocampal function

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Early midlife ovarian removal is associated with lower posterior hippocampal function

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Conflict of interest statement

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