Menopause Marks a Critical Window for Sleep and Mood Care
Mood, sleep, cognition, and brain structure changes in midlife women.
In a UK Biobank analysis of about 125,000 women, menopause was associated with higher self-reported anxiety, depression, and sleep problems, alongside smaller gray matter volumes in memory and emotion-related regions. Women who reported using hormone replacement therapy (HRT) had, on average, higher baseline mental health symptoms and the lowest measured regional brain volumes, suggesting HRT use in this dataset did not clearly offset menopause-linked brain or mental health differences.
Study Details
Menopause is a normal life stage, but many people report mood changes, sleep disruption, and “brain fog.” HRT is widely used for symptom relief, and prescribing has risen in recent years in England.
This creates a practical question for patients and clinicians: beyond hot flashes and night sweats, does HRT correlate with better mental health or cognitive outcomes, and are there measurable differences in brain structure?
This new paper in Psychological Medicine analyzed women in the UK Biobank, a large longitudinal research resource recruited in 2006–2010, to compare pre-menopausal women, post-menopausal women who never used HRT, and post-menopausal women who reported HRT use.
Methodology
This was a cross-sectional analysis using UK Biobank questionnaire data, cognitive testing, and MRI in a subset. After exclusions, 124,780 women were included, and about 10,873 had imaging data. Menopause and HRT exposure were based on self-report, including timing details like age at menopause and age started HRT.
Outcomes included multiple depression and anxiety measures, sleep duration and insomnia-related items, several brief cognitive tasks, and MRI-derived gray matter volumes in the hippocampus and entorhinal cortex (medial temporal lobe) and the anterior cingulate cortex.
Models adjusted for factors such as age, BMI, smoking, education, income, and menopause/HRT timing variables; imaging analyses also adjusted for total intracranial volume.
Key Findings
Menopause status was associated with higher reported anxiety, depression, and sleep difficulties compared with pre-menopause.
The HRT group reported more mental health challenges than post-menopausal women not using HRT; post-hoc work suggested higher pre-existing symptoms among women later prescribed HRT, pointing to confounding by indication as a likely contributor.
In brain imaging, medial temporal lobe and anterior cingulate volumes were smaller in post-menopausal vs pre-menopausal women, with the lowest volumes in the HRT group in this dataset.
Cognitive task results were largely similar across groups, with limited differences that were small in magnitude in the context of the overall sample.
Implications for Practice
For patients, the take-home is not “HRT is harmful.” This design cannot prove causality, and the authors’ own post-hoc work points toward baseline differences: women with more mood symptoms may be more likely to seek care and receive HRT, which can make the HRT group look worse even if treatment is neutral or helpful for some symptoms.
What this paper does reinforce is that menopause is a legitimate window of vulnerability for sleep and mood problems, and those symptoms merit direct, evidence-based treatment rather than being minimized.
For clinicians, this is a reminder to separate two questions in shared decision-making: 1. Whether HRT is appropriate for vasomotor and menopause-related symptoms? and 2. How to address concurrent anxiety, depression, and insomnia with targeted approaches?
In observational datasets, “HRT users” can differ systematically from non-users, so real-world associations should be interpreted cautiously, especially when patients arrive with complex symptom clusters.