Menopause Linked to Mental Health Changes and Gray Matter Loss Unmitigated by HRT: Study

A new study published in the journal of Psychological Medicine showed that menopause is linked to decreased gray matter volume and worse mental health outcomes.

Menopausal symptoms are increasingly being treated with hormone-replacement therapy (HRT), which replaces diminishing ovarian hormones. The use of HRT has increased significantly in England in recent years, and NICE guidelines suggest that it be taken into account for symptoms like depression and sleep issues. Research indicates that there are fewer distinctions between pre- and post-menopausal depression symptoms and that they are more prevalent during the perimenopausal stage. Although results from randomized controlled trials show that HRT is beneficial for vasomotor symptoms, its effects on the brain and mental health are still unknown.

The evidence on estrogen exposure and cognitive deterioration is mixed. Some studies link early menopause or hysterectomy to an increased risk of dementia, while others show that extended lifetime hormone exposure results in improved cognitive outcomes. Similarly, research on HRT shows both increased dementia risk and possibly protective effects, underscoring the persistent uncertainty. Thus, this study looked into how menopause and hormone replacement therapy affect mental health, cognitive function, and brain shape.

In order to evaluate relationships between menopause, HRT use, and outcomes pertaining to mental health, cognition, and brain morphology, researchers examined data from around 125,000 persons in the UK Biobank. In particular, they examined gray matter quantities in the anterior cingulate cortex (ACC) and medial temporal lobe (MTL).

Anxiety, depression, and trouble sleeping have all been linked to menopause. When compared to postmenopausal women who did not use HRT, women who did reported more mental health issues. Women who were taken HRT had greater levels of pre-existing mental health problems, according to post-hoc studies.

In terms of brain anatomy, postmenopausal women had smaller MTL and ACC volumes than premenopausal women, with the HRT group having the lowest volumes. Overall, menopause is associated with poor mental health outcomes and decreased gray matter volume in important brain regions. Because of underlying baseline disparities, the use of HRT does not seem to lessen these effects and may be linked to more severe mental health issues.

Source:

Zuhlsdorff, K., Langley, C., Bethlehem, R., Warrier, V., Romero Garcia, R., & Sahakian, B. J. (2026). Emotional and cognitive effects of menopause and hormone replacement therapy. Psychological Medicine, 56(e24), e24. https://doi.org/10.1017/S0033291725102845