Menopause is Associated With the Loss of Gray Matter in Important Regions of the Brain

New findings from the University of Cambridge suggest that menopause is associated with changes in brain structure and increased levels of anxiety, depression, and sleep disorders. The researchers found reduced gray matter volume in several key brain regions in women who had gone through menopause. The study, published in Psychological Medicine, also examined the effects of hormone replacement therapy (HRT). While HRT did not appear to prevent these changes in the brain or mental health, it was associated with a slower decline in reaction speed.

Understanding Menopause and its Symptoms

Menopause is the stage of life when a woman’s menstrual periods permanently stop due to declining hormone levels. It usually occurs between the ages of 45 and 55 and is often accompanied by symptoms such as hot flashes, depression, and sleep disturbances. Previous research has also found a link between menopause and changes in cognitive abilities, including memory, attention, and language.

To alleviate the symptoms associated with menopause, particularly depression and sleep disturbances, many women are advised to undergo hormone replacement therapy (HRT). In England, HRT was used by 15% of all women in 2023. Despite its widespread use, scientists still have limited knowledge about how menopause and HRT affect the brain, thinking ability, and mental health.

A Large-Scale Study Using Data from the UK Biobank

To better understand these effects, researchers analyzed data from the UK Biobank, which included nearly 125,000 women. Participants were divided into three groups: women who had not yet reached menopause, women who had already reached menopause and had never received hormone replacement therapy, and women who had already reached menopause and had used hormone replacement therapy.

The participants completed questionnaires on menopausal symptoms, mental health, sleep habits, and general health. Some also completed cognitive tests that measured memory and reaction time. In addition, approximately 11,000 women underwent magnetic resonance imaging (MRI), which allowed researchers to examine differences in brain structure.

The average age of participants at the onset of menopause was approximately 49.5 years. Women who were prescribed hormone replacement therapy typically began treatment at around 49 years of age.

Anxiety, Depression, and Sleep Disorders After Menopause

Women who had gone through menopause were more likely than women who had not yet reached menopause to seek help from a family doctor or psychiatrist for anxiety, nervousness, or depression. They also scored higher on questionnaires about depression and were more likely to be prescribed antidepressants.

Women in the HRT group showed higher levels of anxiety and depression compared to women who did not use HRT. However, further analysis revealed that these differences were already present before the onset of menopause. According to the researchers, this suggests that some family doctors may have prescribed HRT in anticipation that menopause could exacerbate existing symptoms.

Sleep problems were also more common after menopause. Postmenopausal women reported insomnia, reduced sleep, and persistent fatigue more often. Women using hormone replacement therapy (HRT) reported feeling the most exhausted of all three groups, even though their total sleep duration did not differ from that of postmenopausal women who did not receive HRT.

Reaction Time Slows Down, While Memory Remains Stable

Dr. Christelle Langley from the Department of Psychiatry said: “Most women go through menopause, and this can be a life-changing event, regardless of whether they receive hormone replacement therapy or not. A healthy lifestyle—for example, exercising, staying active, and eating a healthy diet—is particularly important during this time to mitigate some of the effects. However, we all need to be more sensitive to the physical and mental health of women going through menopause and recognize when they are struggling. There should be no reason to feel embarrassed about telling others what you are going through and asking for help.”

Menopause has also been linked to changes in cognitive performance. Postmenopausal women who did not receive hormone replacement therapy showed slower reaction times compared to those who had not yet reached menopause and those who received hormone replacement therapy. There was no significant difference in memory performance between the three groups.

Dr. Katharina Zühlsdorff from the Department of Psychology at the University of Cambridge said: “As we age, our reaction time tends to slow down – this is simply part of the natural aging process and affects both women and men. Imagine being asked a question in a quiz—you may still come up with the right answer, as you did when you were younger, but younger people would undoubtedly come up with it much faster. Menopause seems to accelerate this process, but hormone replacement therapy seems to slow it down and slow the aging process somewhat.”

Loss of Gray Matter in Brain Regions Associated with Memory and Emotions

Imaging of the brain revealed that women after menopause had a significant reduction in gray matter volume, regardless of whether they had used hormone replacement therapy (HRT). Gray matter contains nerve cell bodies and plays an important role in processing information, controlling movement, and supporting memory and emotion regulation.

The areas most affected included the hippocampus (responsible for forming and storing memories), the entorhinal cortex (the “gateway” for information exchange between the hippocampus and the rest of the brain), and the anterior cingulate cortex (a part of the brain that helps you control emotions, make decisions, and focus your attention).

Professor Barbara Sahakian, lead author of the study from the Department of Psychiatry, added: “The brain regions where we found these differences are those that tend to be affected by Alzheimer’s disease. Menopause could make these women more vulnerable later on. While this is not the whole story, it could help explain why we see almost twice as many cases of dementia in women as in men.”