The study is published by the United Kingdom (UK) publication “The Times”. The work of scientists from the University of East Anglia and the University of Exeter was published in the peer-reviewed scientific journal “Alzheimer’s & Dementia”.
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Observed for more than 13 years
Scientists analyzed data from 183,450 postmenopausal women collected in the UK biobank. The average observation period was 13.3 years, during which dementia was diagnosed in 3,948 women. Of these, 1,993 were diagnosed with Alzheimer’s disease.
Researchers evaluated women who used hormone replacement therapy for at least one year and compared their results with participants who never underwent this treatment.
It turned out that hormone therapy use was associated with a 10% lower risk of all forms of dementia. The risk of Alzheimer’s disease among women who underwent this treatment was 16% lower.
No association was found with other forms of dementia not caused by Alzheimer’s disease.
Timing of treatment is important
The study results suggest that not only the treatment itself but also the woman’s age when it is started may be significant.
The greatest possible benefit was observed among women who started taking hormones between the ages of 46 and 56. Starting treatment at an age older than 56 showed no such association with a lower risk of dementia.
Further analysis of the data revealed that women who started hormone therapy at 46–50 years had a 13% lower risk of dementia, and those who started at 51–56 years had a 23% lower risk compared to participants who never underwent this treatment.
These results support the so-called “window of opportunity” hypothesis. According to it, the effect of hormone therapy on the brain may depend on whether the treatment is started during the perimenopausal period or shortly after menopause.
The association was strongest after surgical menopause
Even more pronounced differences were observed among women who experienced surgical menopause, for example, after removal of both ovaries. In this group, hormone therapy was associated with a 26% lower risk of dementia.
A lower risk was also found in women whose natural lifetime exposure to estrogens was shorter – for example, if menstruation started later or menopause occurred earlier.
Scientists also evaluated genetic factors. Among women carrying the APOE ε4 gene variant, hormone therapy was associated with a 13% lower risk of dementia. This gene variant is considered one of the most important known risk factors for Alzheimer’s disease.
Why are estrogens important for the brain?
Before menopause, estrogens participate in many brain-important processes. They are related to the maintenance of neural connections, glucose utilization, neurotransmitter activity, brain blood flow, the condition of the blood-brain barrier, and regulation of inflammatory processes.
During menopause, the amount of estrogens in the body decreases. Scientists consider that for some women these hormonal changes may be significant for later cognitive function and dementia risk, but the exact mechanism is not yet fully understood.
The study does not prove a protective effect
Although the study was large and women were observed for a long time, it was observational in nature. This means that scientists found an association but cannot confirm that hormone therapy itself reduced the risk of dementia.
The results could also have been influenced by other differences between women who used hormone therapy and those who did not – health status, education, social and economic status, lifestyle, or access to healthcare services.
Moreover, previous research results are inconsistent. Some studies found a possible positive effect, while others did not observe a significant association between menopausal hormone therapy and dementia risk.
Therefore, this treatment should not currently be started solely to protect against dementia. The study results are also not a basis for independently stopping, starting, or changing already prescribed treatment.
Hormone replacement therapy is primarily prescribed to treat menopausal symptoms, and the decision is made individually.
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