Menopause Increases Brain Estrogen Receptors, Affecting Memory and Mood

As women go through menopause, the amount of estrogen receptors (ER) in their brains increases. This change is linked to both reproductive and cognitive functions, regardless of their age or hormone levels, according to data found in a new study published in Nature.

This study also found that higher ER density could tell whether a woman is premenopausal or postmenopausal, and that it’s related to lower memory scores and mood and cognitive issues in postmenopausal women.

Estrogen is a key hormone in the female reproductive system and brain function.

17β-estradiol (E2), the most active form, affects brain processes like cognition and aging by acting on ER in the brain. As women go through menopause, E2 levels drop, impacting these brain functions, the study shared.

However, knowledge of receptor expression and change of aging in the human brain is limited.

To investigate, researchers of the study examined 54 healthy women ages 40 to 65 who were either premenopausal, perimenopausal, or postmenopausal. They used 18F-fluoroestradiol (18F-FES) positron emission tomography (PET) scans to measure ER density in the brains.

PET scans are the only technique currently available that enables in vivo assessment of ER expression, according to researchers.

Participants of the study were recruited at Weill Cornell Medicine between 2021 and 2024.

MRI scans, blood tests for hormone levels and questionnaires about menopausal symptoms were also performed.

Researchers found that as women progress through menopause, ER density in their brains increases, peaking in postmenopausal women. Significant differences in ER density were observed in key brain areas such as the pituitary, PCC and caudate.

These changes were not affected by age but were associated to menopausal status.

Higher ER densities in brain regions involved in cognitive functions were associated with poorer memory performance, especially among postmenopausal women. In addition, increased ER densities were linked to mood swings and cognitive issues in this group.

Voxel-based analyses confirmed a gradual rise in ER densities from premenopausal to postmenopausal stages, particularly in areas like the middle frontal gyrus and anterior cingulate cortex.

Overall, the study highlights how menopause influences the distribution of ERs in the brain and its impact on cognitive and mood-related symptoms.

Study researchers highlighted that this analysis is the first to use brain imaging to explore ER changes during menopause in living humans.

They suggest that future research should include diverse populations and explore genetic and social factors influencing ER.