A reduction in gray matter volume, a kind of “metamorphosis” in the brain’s structure, and higher levels of anxiety and depression, along with sleep disturbances, are among the outcomes identified in a new Cambridge University study published in Psychological Medicine, linking menopause to brain health.
Disturbances typically treated with hormone replacement therapy—the standard of care—but paradoxically, these latest findings suggest that such therapy may not lessen the symptoms, and may only slow the decline in reaction times.
The Study
The research aimed to investigate the effects on depressive symptoms and sleep disorders related to the use of hormone replacement therapy (HRT) during menopause, and to better map how menopause impacts the brain, cognitive function, and mental health. These aspects, not always clearly defined, are central to the English study that analyzed data from the UK Biobank involving nearly 125,000 women, divided into three categories: premenopausal women, postmenopausal women who have never used hormone replacement therapy, and postmenopausal women who have used hormone replacement therapy, in order to fairly compare potential HRT-related factors and avoid bias.
The investigation relied on questionnaires with specific questions about menopause, self-reported mental health, sleep quality and patterns, and general health. In addition, some participants underwent cognitive tests, including memory assessments and reaction-time measurements, and 11,000 of them also underwent magnetic resonance imaging to observe the brain’s structural processes.
The data generally show that postmenopausal women are more likely than premenopausal women to experience anxiety, irritability, or depression, and to score higher on depressive-symptom questionnaires. Consequently, they are more likely to seek care for mood disorders from their primary care physicians or psychiatrists and to be prescribed antidepressants.
Furthermore, among postmenopausal women, insomnia, shorter sleep duration, and fatigue were more frequently observed together. A healthy lifestyle, including regular physical activity and a proper diet, is crucial during menopause and may help mitigate some of these side effects.
Cognitive Outcomes
The menopause appears to have an impact on cognitive function as well; for instance, the study found that those not taking HRT had slower reaction times compared with premenopausal women or those on therapy. As people age, reaction times slow physiologically in both women and men, but menopause seems to accelerate this process.
Conversely, HRT seems to act as a brake, modestly slowing the aging process. There were no meaningful differences across the three groups in memory tasks. However, the study highlighted a notable impact on gray matter volume—the brain tissue that houses nerve cell bodies and is involved in processing information, movement control, and the management of memory and emotions.
In both postmenopausal groups, differences in gray matter volume were observed in several specific brain regions: the hippocampus, which is crucial for forming and storing memories; the entorhinal cortex, the gateway for information flow between the hippocampus and the rest of the brain; and the anterior cingulate cortex, the part of the brain that helps regulate emotions, make decisions, and maintain attention. These areas are also among those most exposed to signs of Alzheimer’s disease, according to the study.
The findings suggest that menopause is linked to negative mental health outcomes and to reductions in gray matter volume in key brain regions. The use of HRT does not appear to lessen these effects and may be associated with more pronounced mental health issues, potentially reflecting underlying baseline differences.
Although preliminary, these results may help illuminate the neurobiological effects of HRT and underscore an unmet need in the diagnosis and treatment of mental health problems during this life stage for women. While not comprehensive, the finding could help explain why women experience nearly twice as much dementia as men.
Source
Zühlsdorff K, Langley C, Bethlehem R, et al. Emotional and cognitive effects of menopause and hormone replacement therapy. Psychological Medicine, 2026, 56, e24, 1–11.
