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Removing ovaries before menopause may accelerate brain degeneration
Last reviewed: 02.07.2025
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Removal of both ovaries before natural menopause is associated with cognitive decline in older age. However, it remains unclear what pathological changes in the brain contribute to these symptoms.
A recent study published in the journal Alzheimer's & Dementia examines white matter integrity after premenopausal bilateral oophorectomy (PBO) in different age groups.
After PBO, there is a significant decrease in the levels of estrogen, progesterone and testosterone, which are produced by the ovaries, with a simultaneous increase in the level of gonadotropins.
Women show higher fractional anisotropy (FA) values in white matter magnetic resonance imaging (MRI) than men, which may be related to sex hormone exposure rather than genetic sex. Women also show higher volumes of white matter hyperintensities (WMH) starting in midlife.
Previous studies have shown that women have an increased risk of developing dementia and cognitive impairment after PBO. However, the brain changes caused by PBO are poorly understood, which motivated the current neuroimaging study.
All study participants were women who had undergone PBO at different ages. Specifically, 22 women had undergone PBO before age 40, 43 and 39 women had undergone PBO at the age of 40 to 45 and 46 to 49, respectively.
Predominant menopause was considered to have occurred if a woman underwent PBO before the age of 40, and early menopause was considered to have occurred if PBO was performed between the ages of 40 and 45.
The control group included 907 women who had not undergone PBO before age 50. Compared with the control group, all women after PBO used estrogen replacement therapy (ERT) with equine estrogens more often and for a longer period of time.
Most women who underwent PBO had no indication for ovarian surgery. Brain MRI scanning was used to assess and compare FA, mean diffusivity (MD), and WMH volumes in different brain regions.
Compared with controls, women who underwent PBO before age 40 had lower FA in the anterior corona radiata, genu of the corpus callosum, and superior occipital white matter. Women after PBO also had higher MD in the corona radiata, genu of the corpus callosum, inferior fronto-occipital fasciculus, posterior thalamic radiation, superior temporal, and superior occipital white matter.
Even after accounting for the use of hormone replacement therapy, the results remained significantly different between the PBO group and the control group.
Similar but less pronounced changes were observed in women who underwent PBO at the age of 45 to 49 years. However, such changes were not observed in women who underwent PBO at the age of 40 to 45 years.
The presence of the apolipoprotein ɛ4 gene (APOE ɛ4) is an independent risk factor for white matter loss. In the present study, adjustment for APOE ɛ4 did not change the results. Similarly, adjustment for cardiovascular risk factors, use of hormone replacement therapy, gravidarum, or hormonal contraception also did not affect the results.
The present study suggests a reduction in white matter integrity that extends across multiple brain regions in women who experienced PBO before age 40.
These findings support previous studies showing volume reductions in the amygdala, hippocampus, and other white matter regions of the brain that are associated with vascular dementia more than Alzheimer's disease (AD). Some of the observed changes in the temporal lobes are also consistent with AD.
The decrease in white matter integrity may be related to loss of androgens rather than estrogens; however, this requires further verification. Future studies with larger cohorts are needed to examine the effect of estrogen replacement therapy other than equines, which were used in the present study participants.