Menopause is linked to reduced gray matter and increased anxiety

New research suggests that menopause is accompanied by distinct changes in the brain’s structure and a notable increase in mental health challenges. While hormone replacement therapy appears to aid in maintaining reaction speeds, it does not seem to prevent the loss of brain tissue or alleviate symptoms of depression according to this specific dataset. These observations were published online in the journal Psychological Medicine.

Menopause represents a major biological transition marked by the cessation of menstruation and a steep decline in reproductive hormones. Women frequently report a variety of symptoms during this time, ranging from hot flashes to difficulties with sleep and mood regulation.

Many individuals turn to hormone replacement therapy to manage these physical and psychological obstacles. Despite the common use of these treatments, the medical community still has questions about how these hormonal shifts affect the brain itself. Previous research has yielded mixed results regarding whether hormone treatments protect the brain or potentially pose risks.

To clarify these effects, a team of researchers from the University of Cambridge undertook a large-scale analysis. Katharina Zuhlsdorff, a researcher in the Department of Psychology at the University of Cambridge, served as the lead author on the project.

She worked alongside senior author Barbara J. Sahakian and colleagues from the Departments of Psychiatry and Psychology. Their objective was to provide a clearer picture of how the end of fertility influences mental well-being, thinking skills, and the physical architecture of the brain.

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The team utilized data from the UK Biobank, a massive biomedical database containing genetic and health information from half a million participants. For this specific investigation, they selected a sample of nearly 125,000 women.

The researchers divided these participants into three distinct groups to allow for comparison. These groups included women who had not yet gone through menopause, post-menopausal women who had never used hormone therapy, and post-menopausal women who were users of such therapies.

The investigation first assessed psychological well-being across the different groups. The data showed that women who had passed menopause reported higher levels of anxiety and depression compared to those who had not.

Sleep quality also appeared to decline after this biological transition. The researchers observed that women taking hormone replacement therapy actually reported more mental health challenges than those who did not take it. This group also reported higher levels of tiredness.

This result initially seemed counterintuitive, as hormone therapy is often prescribed to help with mood. To understand this, the authors looked backward at the medical history of the participants. They found that women prescribed these treatments were more likely to have had depression or anxiety before they ever started the medication. This suggests that doctors may be prescribing the hormones specifically to women who are already struggling with severe symptoms.

The study also tested how quickly the participants could think and process information. The researchers found that reaction times typically slow down as part of the aging process.

However, menopause seemed to speed up this decline in processing speed. In this specific domain, hormone therapy appeared to offer a benefit. Post-menopausal women taking hormones had reaction times that were faster than those not taking them, effectively matching the speeds of pre-menopausal women.

Dr. Katharina Zühlsdorff noted the nuance in these cognitive findings. She stated, “Menopause seems to accelerate this process, but HRT appears to put the brakes on, slowing the ageing process slightly.”

While reaction times varied, the study did not find similar differences in memory performance. The researchers administered tasks designed to test prospective memory, which is the ability to remember to perform an action later. They also used a digit-span task to measure working memory capacity. Across all three groups, performance on these memory challenges remained relatively comparable.

A smaller subset of about 11,000 women underwent magnetic resonance imaging scans to measure brain volume. The researchers focused on gray matter, the tissue containing the body of nerve cells. They specifically looked at regions involved in memory and emotional regulation. These included the hippocampus, the entorhinal cortex, and the anterior cingulate cortex.

The hippocampus is a seahorse-shaped structure deep in the brain that is essential for learning and memory. The entorhinal cortex functions as a gateway, channeling information between the hippocampus and the rest of the brain. The anterior cingulate cortex plays a primary role in managing emotions, impulse control, and decision-making.

The scans revealed that post-menopausal women had reduced gray matter volume in these key areas compared to pre-menopausal women. This reduction helps explain the higher rates of mood issues in this demographic. Unexpectedly, the group taking hormone therapy showed the lowest brain volumes of all. The treatment did not appear to prevent the loss of brain tissue associated with the end of reproductive years.

The specific regions identified in the study are often implicated in neurodegenerative conditions. Professor Barbara Sahakian highlighted the potential long-term importance of this observation. She explained, “The brain regions where we saw these differences are ones that tend to be affected by Alzheimer’s disease. Menopause could make these women vulnerable further down the line.”

While the sample size was large, the study design was observational rather than experimental. This means the researchers could identify associations but cannot definitively prove that menopause or hormone therapy caused the changes.

The UK Biobank population also tends to be wealthier and healthier than the general public, which may skew the results. Additionally, the study relied on self-reported data for some measures, which can introduce inaccuracies.

The finding regarding hormone therapy and lower brain volume is difficult to interpret without further research. It remains unclear if the medication contributes to the reduction or if the women taking it had different brain structures to begin with.

The researchers emphasize that more work is needed to disentangle these factors. Future studies could look at genetic factors or other health conditions that might influence how hormones affect the brain.

Despite these limitations, the research highlights the biological reality of menopause. It confirms that the transition involves more than just reproductive changes.

Christelle Langley emphasized the need for broader support systems. She remarked, “We all need to be more sensitive to not only the physical, but also the mental health of women during menopause, however, and recognise when they are struggling.”

The study, “Emotional and cognitive effects of menopause and hormone replacement therapy,” was authored by Katharina Zuhlsdorff, Christelle Langley, Richard Bethlehem, Varun Warrier, Rafael Romero Garcia, and Barbara J Sahakian.