Menopause Goes Beyond Hot Flashes: Impacts on The Brain and Mental Health

Menopause is associated with significant changes in mental health, sleep, cognition, and brain structure. While hormone replacement therapy is effective in alleviating physical symptoms, its psychological benefits are unclear and appear to vary among women. Results suggest that women using hormone replacement therapy may already experience more mental health challenges before treatment. These findings highlight the need to view menopause not only as a hormonal issue but also as a critical period for women's mental health care.

Menopause is a natural phase in a woman's life, but it brings a number of significant physical and emotional changes. Hot flashes, mood swings, sleep problems, and fatigue are some of the most common symptoms. In addition, many women report difficulties with memory, concentration, and attention during this period. Although menopause is an expected event of aging, its effects on the brain and mental health are not yet fully understood.

To alleviate symptoms, many women resort to hormone replacement therapy (HRT), which replaces hormones such as estrogen, whose production declines after menopause. The use of hormone replacement therapy has grown in recent years, especially to reduce physical symptoms such as hot flashes and night sweats.

However, while hormone replacement therapy is considered effective for these physical symptoms, many questions remain about its effects on mood, sleep, cognition, and broader mental health.

Scientific studies on estrogen, menopause, and cognition show contradictory results. Some research suggests that early loss of ovarian hormones may increase the risk of dementia and cognitive decline. Others indicate that greater exposure to estrogen throughout life may protect the brain and slow this decline.

The same is true for hormone replacement therapy: while some studies point to risks, others suggest beneficial effects, showing that the relationship between hormones and the brain is complex and likely depends on individual factors such as age, health history, and the timing of treatment initiation.

When it comes to mental health, the scenario is even more nebulous. Evidence indicates that symptoms of anxiety, depression, and sleep disorders become more frequent after menopause. Some women report worsening mood and increased insomnia, which can significantly affect their quality of life.

Interestingly, population studies have observed that postmenopausal women who use hormone replacement therapy, on average, report more mental health symptoms than those who do not. This raises an important question: is hormone replacement therapy causing these symptoms, or is it being used more by women who already experienced greater psychological distress?

To try to answer these questions, this study analyzed data from nearly 125,000 women, comparing three groups: premenopausal women, postmenopausal women who never used hormone replacement therapy, and postmenopausal women who used hormone replacement therapy.

Aspects such as sleep duration and quality, fatigue levels, symptoms of anxiety and depression, and performance on memory tasks were evaluated. In addition, a subset of the participants underwent brain imaging exams.

The analyses showed that menopause is associated with more emotional difficulties, worse sleep, and greater fatigue. Women who used hormone replacement therapy reported, on average, more symptoms of anxiety and depression than those who did not.

However, more detailed analyses suggest that these women already presented more symptoms even before starting therapy, indicating that hormone replacement therapy may not be the direct cause of these problems, but rather a marker of women who were already seeking help because they felt worse.

Brain scans revealed that postmenopausal women showed a reduction in gray matter volume in important brain regions, such as the hippocampus, involved in memory, and the anterior cingulate cortex, related to emotional regulation.

These reductions were more pronounced in the group using hormone replacement therapy, although, again, this may reflect pre-existing differences between the groups, and not necessarily a direct negative effect of hormone treatment.

READ MORE:

Emotional and cognitive effects of menopause and hormone replacement therapy

Katharina Zuhlsdorff, Christelle Langley, Richard Bethlehem, Varun Warrier, Rafael Romero Garcia, and Barbara J Sahakian

Psychological Medicine. 27 January 2026; 56 : e24. 

DOI: 10.1017/S0033291725102845

Abstract:

Menopause is a natural physiological process, but its effects on the brain remain poorly understood. In England, approximately 15% of women use hormone-replacement therapy (HRT) to manage menopausal symptoms. However, the psychological benefits of HRT are not well established. This study aims to investigate the impact of menopause and HRT on mental health, cognitive function, and brain structure. We analyzed data from nearly 125,000 participants in the UK Biobank to assess associations between menopause, HRT use, and outcomes related to mental health, cognition, and brain morphology. Specifically, we focused on gray matter volumes in the medial temporal lobe (MTL) and anterior cingulate cortex (ACC). Menopause was associated with increased levels of anxiety, depression, and sleep difficulties. Women using HRT reported greater mental health challenges than post-menopausal women not using HRT. Post-hoc analyses revealed that women prescribed HRT had higher levels of pre-existing mental health symptoms. In terms of brain structure, MTL and ACC volumes were smaller in post-menopausal women compared to pre-menopausal women, with the lowest volumes observed in the HRT group. Our findings suggest that menopause is linked to adverse mental health outcomes and reductions in gray matter volume in key brain regions. The use of HRT does not appear to mitigate these effects and may be associated with more pronounced mental health challenges, potentially due to underlying baseline differences. These results have important implications for understanding the neurobiological effects of HRT and highlighting the unmet need for addressing mental health problems during menopause.