Women who use estrogen-only hormone therapy during menopause may have fewer brain changes associated with Alzheimer’s disease, according to a study published in Neurology. Researchers found links between the therapy, reduced disease-related pathology in brain tissue, lower odds of a dementia diagnosis and stronger performance on some memory tests.
The study examined records from two large databases. Using data from the National Alzheimer’s Coordinating Center, Jennifer L. Bruno of Stanford University and colleagues analyzed autopsy records from 2,959 women aged 50 and older. Among them, 258 had reported using estrogen-only menopausal hormone therapy. Women who had used combined estrogen and progestin therapy were excluded from the main analysis.
The autopsies showed that estrogen-only users had lower odds of advanced Alzheimer’s pathology when they died. Their brains also contained fewer signs of cerebrovascular disease, including small strokes and damaged blood vessels. In a secondary analysis, the association with lower pathology was linked to conjugated estrogens rather than estradiol.
The researchers also reviewed clinical records for 1,841 hormone therapy users and 17,561 non-users. The therapy users had lower odds of receiving a clinical dementia diagnosis and showed fewer symptoms involving memory and functional decline.
A separate analysis used data from the Alzheimer’s Disease Neuroimaging Initiative. It included 110 women who used estrogen-only therapy and 1,948 who did not. Users had higher levels of amyloid-beta 42 in their blood and cerebrospinal fluid. In these fluids, higher levels of this protein indicate that less amyloid has been deposited in the brain as Alzheimer’s-related plaques. However, positron emission tomography scans did not show a difference in amyloid accumulation between the groups.
Women who used the therapy also scored higher on tests of immediate verbal memory and learning. Exploratory genetic analyses found that the association with less brain pathology was present only among women who did not carry the APOE e4 variant, a known Alzheimer’s risk factor. The lower likelihood of a dementia diagnosis, however, appeared in both genetic groups.
The researchers stressed that the study was observational and cannot show that estrogen therapy caused the differences. Women who choose hormone therapy may differ from non-users in their general health, access to healthcare or lifestyle. Other unmeasured factors could also explain some of the findings.
The results may not apply to the combined hormone treatments used by most women receiving menopausal therapy. Estrogen-only treatment is generally prescribed to women who have had their uterus removed, because estrogen without progesterone can raise the risk of uterine cancer. The average age at which participants reported using hormone therapy was about 70, whereas current guidelines generally recommend starting treatment around the beginning of menopause and stopping by age 60.
The authors said controlled studies that follow patients over time are needed to clarify how menopausal hormone therapy affects Alzheimer’s-related biological changes and to help assess its risks and potential benefits.
Sources: PsyPost.