Women who received estrogen-only hormone therapy around menopause had lower odds of showing the brain changes associated with Alzheimer’s disease, according to a new study.
Researchers analysed health records and brain autopsy results from more than 5,000 older women who had undergone hysterectomies and subsequently died. Those who had received estrogen-only therapy had 35% lower odds of having the characteristic signs of Alzheimer’s, including amyloid plaques, compared with women who had not received estrogen therapy.
The findings, published in Neurology, provide new evidence in the long-running debate over whether maintaining estrogen levels after menopause could influence the risk of Alzheimer’s disease.
Researchers say the use of brain autopsy results gives the study a more objective measure of Alzheimer’s-related changes than research based solely on cognitive decline or clinical assessments.
Findings add to mixed evidence
Previous research into hormone therapy and Alzheimer’s disease has produced conflicting results, with some studies suggesting a reduced risk and others finding no benefit or an increased risk.
The landmark Women’s Health Initiative hormone therapy trial, whose initial results were published in 2002, raised concerns about the safety of hormone therapy after finding increased risks of breast cancer and dementia. It did not find a reduction in Alzheimer’s risk.
However, researchers behind the new study note that the Women’s Health Initiative involved post-menopausal women and used a different hormone treatment approach, making its findings difficult to apply directly to women who begin therapy around the time of menopause.
The women in the new study received estrogen alone rather than a combination of estrogen and progesterone. Estrogen-only therapy can be prescribed to women who have undergone a hysterectomy because they do not need progesterone to protect the lining of the uterus.
This allowed researchers to examine the potential effects of estrogen itself, including its possible effects on the brain.
Researchers caution against drawing conclusions
Despite the findings, the researchers stressed that the study does not establish that estrogen therapy prevents Alzheimer’s disease.
Hadi Hosseini, an associate professor of psychiatry at Stanford University and a co-author of the study, said the results do not demonstrate a cause-and-effect relationship between estrogen and Alzheimer’s.
The study also did not establish when participants began taking estrogen, which specific formulation they used or how long they continued treatment.
Researchers say these factors could be important in understanding the relationship between hormone therapy and later Alzheimer’s risk.
They are calling for further research, including studies that follow women from the period immediately before menopause through menopause while monitoring Alzheimer’s-related biomarkers in blood and spinal fluid, as well as changes visible in brain imaging.
Such research could help clarify whether the timing, formulation and duration of hormone therapy influence its potential effects on Alzheimer’s disease.
