A US analysis using data from more than 20 000 women found that use of a specific form of hormone therapy in later life was linked to “significantly lower odds of a clinical dementia diagnosis”, reports The Independent.
According to the team’s research, older women on this specific HRT may have a lower risk of exhibiting physical signs of Alzheimer’s disease within the brain.
Those prescribed oestrogen-only HRT were found to have a decreased likelihood of developing dementia, the study observed, and additionally, were less prone to memory loss or experiencing functional decline.
However, experts cautioned that the conclusions “cannot necessarily be applied to all women considering hormone replacement therapy today”, as oestrogen-only treatments are usually offered solely to women who have had a hysterectomy.
For their study, published in Neurology, researchers from Stanford University in the United Stated evaluated data from two major national databases tracking Alzheimer’s disease.
The data from 21 462 women showed that use of this hormone therapy in later life was linked to “significantly lower odds of a clinical dementia diagnosis” – with women on the treatment seeing a 39% reduced risk compared with non-users.
They also had 33% lower odds of symptoms of memory/functional decline.
Post-mortem data from 258 menopause hormone treatment users and 2 701 non-users found 35% lower odds of biological signs of Alzheimer’s in the brain, including plaque build up.
An important limitation is that the women in the study used hormone therapy differently from how it is typically prescribed today. The researchers noted that participants who received hormone therapy had an average age of 70.
Current standard practice generally involves starting hormone therapy in the late 40s to early 50s and stopping treatment before age 60.
“Despite these limitations, our findings provide evidence of an association between use of oestrogen-only hormone therapy during later life and better outcomes on dementia and brain health,” said study author Jennifer Bruno, PhD, of Stanford Medicine.
“This study looked back at women who were using hormone therapy decades ago, with the timing and type of use differing from what is current practice for most women today, so the results are informative, but may not apply to today’s standards.”
Commenting on the study, Dr Tom Blackmore, research programmes manager at Alzheimer’s Research UK, said: “The findings – that women who reported using oestrogen-only hormone therapy at an average age of around 70 were less likely to develop dementia and showed fewer biological signs associated with Alzheimer’s – are interesting, but this study can only show an association. It can’t tell us whether hormone therapy itself reduced dementia risk.
“Many factors influence someone’s likelihood of developing dementia, and women who received the HRT may differ from those who did not in ways that also affect their long-term brain health.
“It’s also important to note that women in this study reported using oestrogen-only hormone therapy at an average age of around 70, differing substantially from how hormone replacement therapy is typically used today.
“This research also focused on oestrogen-only hormone therapy – typically prescribed to women who have had a hysterectomy.
“This means the findings cannot necessarily be applied to all women, considering hormone replacement therapy today.
“These findings are not a reason for women to start or stop hormone replacement therapy with the aim of reducing dementia risk. But it provides valuable clues about the biology underlying dementia and highlights the need for more research into women’s brain health.
“Larger and more diverse studies will be needed to determine whether hormone-based treatments could play any role in reducing dementia risk.”
Dr Richard Oakley, associate director of research and innovation at Alzheimer’s Society, said: “Around two-thirds of people who have Alzheimer’s disease in the UK today are women, and while we still don’t fully understand why they are more susceptible than men, it is thought that hormones may play a role.”
Study details
Association Between Menopausal Hormone Therapy and Alzheimer Disease Neuropathology
Jennifer Bruno, Jacob Shaw, SM Hadi Hosseini.
Published in Neurology on 8 September 2026
Abstract
Background and Objectives
Although evidence suggests that the neurophysiologic impact of oestrogen decline during menopause may contribute to increased risk of Alzheimer disease (AD) in women, the effect of menopausal hormonal therapy (MHT) on AD risk requires further study. We sought to examine the associations between MHT use and neuropathologic, clinical, and imaging/fluid biomarker outcomes.
Methods
In this cohort study, we tested the association between oestrogen-only MHT use and dementia outcomes in female participants using two independent, large-scale data sets: National Alzheimer's Co-ordinating Centre (NACC) and Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants included women 50 and older with self-reported use of oestrogen-only MHT or no self-reported use of MHT. Clinical, imaging/fluid biomarker, and neuropathologic outcomes were examined. Research was performed at academic medical centres.
Results
Neuropathologic data were collected from NACC for 258 MHT users (mean age of death = 81.9, SD = 19.5) and 2,701 non-MHT users (mean age of death = 82.2, SD = 11.0). The ADNI cohort included 110 MHT users (mean age = 76.5, SD = 7.5) and 1,948 non-MHT users (mean age = 73.2, SD = 8.9). The odds of increased AD pathology on autopsy (primary outcome) were significantly decreased in MHT users relative to nonusers (odds ratio [OR] 0.65, 95% CI 0.48–0.88, p = 0.005). MHT use was associated with secondary outcomes including significantly decreased amyloid pathologic load assessed through plasma (β = 0.44, 95% CI 0.16–0.73, p = 0.0025) and CSF (β = 0.07, 95% CI 0.002–0.13, p = 0.030). MHT use was associated with significantly lower odds of clinical dementia diagnoses (OR 0.61, 95% CI 0.55–0.67, p < 0.0001) and lower odds of symptoms of memory/functional decline (OR 0.67, 95% CI 0.61–0.74, p < 0.0001).
Discussion
Our findings demonstrate small but significant associations between MHT use during later life and a range of AD-related neuropathologic and clinical outcomes in 2 large cohorts of female participants. Although our results do not address causality and have limited generalisability due to the retrospective nature of the study, they suggest a protective effect of MHT use in the dementia course.
See more from MedicalBrief archives:
More brain changes for post-menopausal than for pre-menopausal women – Bonn study
Early menopause may raise dementia risk later – UK study of 150,000 women
Hormone therapy associated with improved cognition
HRT not linked to increased risk of dementia — Largest study yet