Hormone replacement therapy involves women being given synthetic estrogen to replace declining hormone levels and thus relieve the symptoms of menopause.
But several studies suggest that HRT is a risk factor for several conditions.
A discovery in Liverpool that a gene could ‘drive’ the progression of Alzheimer’s disease in women on HRT casts further doubt on the National Institute for Health and Care Excellence’s (NICE) support for HRT in managing symptoms of menopause.
“We decided to investigate the effects of HRT on cerebrospinal fluid biomarkers associated with Alzheimer’s disease. What we found is that the fluid pathology of the disease is high when HRT use is associated with the presence of an APOE e4 gene variant, but not otherwise.” explains Dr Ainara Jauregi-Zinkunegi, postdoctoral researcher in neuroscience at Liverpool John Moores University and first author.
The gene variant is present in about 1 in 4 people and has previously been linked to the development of dementia.
The team, which published its findings today (January 9, 2025) in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Associationexamined fluid biomarker data from 136 women – mean age: 66 – with no cognitive problems, and compared HRT users with non-users, including whether they carried the APOE e4 variant.
Although mean levels of phosphorylated tau by amyloid beta-42, a measure of AD pathology, were similar among HRT users and nonusers, regardless of APOE e4, women using HRT who had at least one APOE e4 allele , levels of the same biomarker that were more than 60% higher.
They concluded that elevated levels of these biomarkers likely indicate increased Alzheimer’s disease-related pathology in these women and thus a higher risk of developing dementia. HRT was not associated with higher biomarker levels in the absence of APOE e4.
If our results are confirmed (in further studies), they would warn against the use of HRT in women at increased risk of Alzheimer’s disease due to genetic susceptibility.
People who are already at increased risk for AD, such as those with the e4 variant of APOE, even if they are currently asymptomatic, may be more sensitive to potential negative effects of hormone replacement.
There is still much we do not know, but it may be prudent to test women for the presence of the APOE e4 variant before administering HRT, at least until more knowledge is gained on this issue.”
Dr. Davide Bruno, Reader in Neuropsychology, Liverpool John Moores University
And he added: “We think this could be a scenario where estrogen exposure could benefit healthy neurons, but estrogen could instead worsen damage to ‘sick’ neurons.”
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