A study published August 12 in Neurology analyzed data from more than 5,000 women over age 50 who participated in cognitive testing during life and donated their brains for examination after death. Researchers led by Stanford University neuroscientist Hadi Hosseini focused on the roughly 7 percent of participants who used estrogen-only hormone therapy, typically prescribed after hysterectomy.
The team examined three hallmark signs of Alzheimer's disease: amyloid plaques, tau-related neurofibrillary tangles, and neuritic plaques. These protein accumulations in and around neurons are considered reliable postmortem indicators of the disease, unlike cognitive tests or blood biomarkers which can be ambiguous.
Women who had used estrogen-only therapy had 35 percent lower odds of severe Alzheimer's markers at autopsy than nonusers. During life, these women also showed lower amyloid levels in blood and cerebrospinal fluid, as well as lower odds of memory loss or functional decline.
Previous studies of menopausal hormone therapy have produced conflicting results, with some suggesting protection against dementia and others showing no benefit or potential harm, particularly when therapy begins after age 65. Many earlier studies relied on cognitive measures or blood tests rather than direct brain examination.
The researchers did not have sufficient data on women taking combined estrogen-progestogen therapy, which is more common for women with intact uteruses, to perform the same analyses. Animal studies suggest estrogen may reduce production of harmful amyloids and aid their clearance, though this study did not investigate those mechanisms.
The authors emphasize the findings do not prove hormone therapy prevents Alzheimer's disease but should spur future clinical trials tracking biomarkers and cognition from menopause onward. Neurologist Gayatri Devi, not involved in the study, called it an important addition to evolving evidence on hormone therapy and brain health.
Developmental psychologist and neuroscientist Jennifer Bruno of Stanford University said the findings highlight the importance of estrogen for brain health and longevity, and that women can advocate for future trials to establish causality.
Estrogen therapy is linked to fewer signs of Alzheimer’s in the brain
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