Association of Bilateral Salpingo-Oophorectomy before Menopause Onset with Medial Temporal Lobe Neurodegeneration

Burcu Zeydan, Nirubol Tosakulwong, Christopher G. Schwarz, Matthew L. Senjem, Jeffrey L. Gunter, Robert I. Reid, Liliana Gazzuola Rocca, Timothy G. Lesnick, Carin Y. Smith, Kent R. Bailey, Val J. Lowe, Rosebud O. Roberts, Clifford R. Jack, Ronald C. Petersen, Virginia M. Miller, Michelle M. Mielke, Walter A. Rocca, Kejal Kantarci

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Importance: There is an increased risk of cognitive impairment or dementia in women who undergo bilateral salpingo-oophorectomy (BSO) before menopause. However, data are lacking on the association of BSO before menopause with imaging biomarkers that indicate medial temporal lobe neurodegeneration and Alzheimer disease pathophysiology. Objective: To investigate medial temporal lobe structure, white matter lesion load, and β-amyloid deposition in women who underwent BSO before age 50 years and before reaching natural menopause. Design, Setting, and Participants: This nested case-control study of women in the population-based Mayo Clinic Cohort Study of Oophorectomy and Aging-2 (MOA-2) and in the Mayo Clinic Study of Aging (MCSA) in Olmsted County, Minnesota, included women who underwent BSO from 1988 through 2007 and a control group from the intersection of the 2 cohorts. Women who underwent BSO and control participants who underwent a neuropsychological evaluation, magnetic resonance imaging (MRI), and Pittsburgh compound B positron emission tomography (PiB-PET) were included in the analysis. Data analysis was performed from November 2017 to August 2018. Exposure: Bilateral salpingo-oophorectomy in premenopausal women who were younger than 50 years. Main Outcomes and Measures: Cortical β-amyloid deposition on PiB-PET scan was calculated using the standard uptake value ratio. White matter hyperintensity volume and biomarkers for medial temporal lobe neurodegeneration (eg, amygdala volume, hippocampal volume, and parahippocampal-entorhinal cortical thickness) on structural MRI and entorhinal white matter fractional anisotropy on diffusion tensor MRI were also measured. Results: Forty-one women who underwent BSO and 49 control participants were recruited. One woman was excluded from the BSO group after diagnosis of an ovarian malignant condition, and 6 women were excluded from the control group after undergoing BSO after enrollment. Twenty control participants and 23 women who had undergone BSO completed all examinations. The median (interquartile range [IQR]) age at imaging was 65 (62-68) years in the BSO group and 63 (60-66) years in the control group. Amygdala volume was smaller in the BSO group (median [IQR], 1.74 [1.59-1.91] cm 3 ) than the control group (2.15 [2.05-2.37] cm 3 ; P <.001). The parahippocampal-entorhinal cortex was thinner in the BSO group (median [IQR], 3.91 [3.64-4.00] mm) than the control group (3.97 [3.89-4.28] mm; P =.046). Entorhinal white matter fractional anisotropy was lower in the BSO group (median [IQR], 0.19 [0.18-0.22]) than the control group (0.22 [0.20-0.23]; P =.03). Women were treated with estrogen in both groups (BSO, n = 22 of 23 [96%]; control, n = 10 of 19 [53%]). Global cognitive status test results did not differ between the groups. Conclusions and Relevance: Abrupt hormonal changes associated with BSO in premenopausal women may lead to medial temporal lobe structural abnormalities later in life. Longitudinal evaluation is needed to determine whether cognitive decline follows.

Original languageEnglish (US)
Pages (from-to)95-100
Number of pages6
JournalJAMA neurology
Issue number1
StatePublished - Jan 2019

ASJC Scopus subject areas

  • Clinical Neurology


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