How Menopause Changes Brain Structure and Connectivity

In this study, researchers use neuroimaging to see how menopause alters brain structure and connectivity in postmenopausal women.

Menopause marks the beginning of the next biological chapter in a woman’s life. Characterized by the natural ebb of reproductive hormones (particularly estrogen), menopause ushers in a new season of aging. This hormonal shift not only signifies a transition in fertility but also influences systemic health. The menopause-associated decline in estrogen has been associated with various health issues, including alterations in brain structure and function. However, the mechanics of this phenomenon are still poorly understood. A greater understanding of how menopause alters the brain could aid in the early detection, and possible prevention, of neurodegenerative disease.

In a new study, researchers Gwang-Won Kim, Kwangsung Park, Yun-Hyeon Kim, and Gwang-Woo Jeong from Chonnam National University used neuroimaging to shed light on how menopause alters brain morphology and functional connectivity in postmenopausal women. On March 23, 2024, their research paper was published as the cover of Aging’s Volume 16, Issue 6, entitled, “Altered brain morphology and functional connectivity in postmenopausal women: automatic segmentation of whole-brain and thalamic subnuclei and resting-state fMRI.” 

“To the best of our knowledge, no comparative neuroimaging study on alterations in the brain volume and functional connectivity, especially focusing on the thalamic subnuclei in premenopausal vs. postmenopausal women has been reported.”

The Study

The decline in estrogen levels during menopause has been linked to an elevated risk of neurodegenerative diseases, notably Alzheimer’s disease (AD). Estrogen plays a pivotal role in modulating neurotransmitter systems, neurotrophins, and brain cytoarchitecture, and there is evidence that these interactions also affect mood, memory, and cognition. The biological mechanisms underlying the increased AD risk in postmenopausal women are not fully understood.

In this study, 21 premenopausal women and 21 postmenopausal women were subjected to magnetic resonance imaging (MRI). The researchers utilized T1-weighted MRI and resting-state functional MRI data to assess differences in brain volume and seed-based functional connectivity. For statistical analysis, they employed multivariate analysis of variance, factoring in age and whole brain volume as covariates, to compare the surface areas and subcortical volumes between the two groups.


Postmenopausal women showed significantly smaller cortical surface, especially in the left medial orbitofrontal cortex (mOFC), right superior temporal cortex (STC), and right lateral orbitofrontal cortex, compared to premenopausal women. These findings suggest that diminished brain volume may be linked to menopause-related symptoms caused by lower sex hormone levels.

In addition to structural changes, the functional connectivity between the brain regions also showed changes. The study found significantly decreased functional connectivity between the left mOFC and the right thalamus in postmenopausal women — reinforcing the hypothesis that the left orbitofrontal-bilateral thalamus connectivity is associated with cognitive impairment. Although postmenopausal women did not show volume atrophy in the right thalamus, the volume of the right pulvinar anterior (PuA), a significant thalamic subnuclei, was significantly decreased. Decreased PuA volume in postmenopausal women is closely related to decreases in female sex hormone levels following menopause.

Expectedly, the study found a significant difference in age and sex hormone levels between premenopausal and postmenopausal women. Postmenopausal women had lower total estrogen and estradiol (E2) levels and higher follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels than premenopausal women. Estrogen levels were positively correlated with the surface area of the left mOFC, right STC, and right lOFC, as well as the volume of the right PuA.

“Concerning the close connection between the estrogen level and STC volume, our findings support a potential role of decreases in sex hormones following menopause due to the correspondent brain structural atrophy. However, further study is needed to elucidate the specific cognitive and emotional implications in connection with these structural changes.”

Conclusions & Future Directions

Postmenopausal women showed significantly lower left mOFC, right lOFC, and right STC surface areas, reduced right PuA volume, and decreased left mOFC-right thalamus functional connectivity compared to premenopausal women. These findings provide novel insight into the structural and functional changes in the brain associated with menopause. However, further research is needed to validate these findings in a larger cohort and to understand the potential cognitive implications of these changes.

“Our findings provide novel insight into the structural and functional changes in the brain associated with menopause.”

Click here to read the full research paper published in Aging.

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