Menopause was associated with worse mental health and reduced gray matter volume in key brain regions, and hormone replacement therapy use did not mitigate these associations, according to a UK Biobank analysis of nearly 125,000 women published in Psychological Medicine.
Both postmenopausal groups reported higher levels of anxiety and depression compared with premenopausal women. The postmenopausal group that had used hormone replacement therapy (HRT) reported greater mental health challenges than the group that had not, including more clinical contact for psychiatric symptoms. Postmenopausal women were also more likely to use antidepressant or anxiolytic medications, though no difference in medication use was observed between HRT users and nonusers.
Postmenopausal women reported higher levels of insomnia and tiredness and shorter sleep duration. Tiredness was highest in the HRT group.
In neuroimaging analyses of 10,873 participants, gray matter volumes in the hippocampus, entorhinal cortex, and anterior cingulate cortex were smaller in postmenopausal women, with the lowest volumes observed in HRT users. Compared with postmenopausal women who had not used HRT, those in the HRT group had additional reductions in hippocampal and anterior cingulate cortex volumes.
A post hoc analysis offered a potential explanation: women who initiated HRT between assessment visits had reported higher levels of psychiatric symptoms at baseline than those who never used HRT, suggesting a pre-existing mental health burden among those prescribed therapy.
Cognitive differences were limited. Processing speed was slower in postmenopausal women who had not used HRT compared with premenopausal women, but no other post hoc comparisons for memory tasks remained statistically significant following correction for multiple testing.
Study Design
Researchers analyzed UK Biobank data from women aged 40 to 69 years recruited between 2006 and 2010. Following exclusions for dementia, hysterectomy, menopause onset prior to age 30 years, and incomplete data, 124,780 women were categorized into three groups: premenopausal, postmenopausal without HRT use, and postmenopausal with HRT use.
Mental health outcomes included clinical contact for anxiety or depression, modified Patient Health Questionnaire-4 and Generalized Anxiety Disorder-7 scores, and ICD-10 diagnoses. Statistical models adjusted for age, socioeconomic factors, body mass index, smoking status, time since menopause onset, and duration of HRT use.
The study investigators reported no relevant financial conflicts of interest.
Source: Psychological Medicine
