Key Summary
- HRT may be associated with reduced risk of dementia, a study found.
- The research tracked 183,450 postmenopausal women.
- Women who experienced surgical menopause, such as bilateral oophorectomy, saw a 26% reduction in dementia risk when taking HRT.
Hormone replacement therapy (HRT) could be associated with a significantly reduced risk of dementia, with the strongest protective effects observed in women who undergo surgical menopause or initiate treatment in early midlife, according to the largest study of its kind to date.
The research, led by the University of East Anglia (UEA) in collaboration with the University of Exeter and published in Alzheimer’s & Dementia, tracked 183,450 postmenopausal women from the UK Biobank over an average follow-up period of 13.3 years.
Overall, women who used HRT for at least one year were 16% less likely to develop Alzheimer’s disease and 10% less likely to develop any form of dementia compared to non-users.
However, the protective effect varied considerably depending on surgical history, genetics, and age of initiation.
Women who experienced surgical menopause, such as bilateral oophorectomy, saw a 26% reduction in dementia risk when taking HRT.
A 16% reduction was also identified among women with naturally lower lifetime oestrogen exposure, including those with later menarche or premature natural menopause.
The study highlighted the significance of the "critical window" hypothesis: women who began HRT between the ages of 46 and 56 experienced the greatest reduction in cognitive decline risk, whereas those initiating treatment outside this window did not see equivalent benefits.
Professor Anne-Marie Minihane, from UEA’s Norwich Medical School and director of the Norwich Institute for Healthy Aging at UEA, led the study.
She said: “Dementia affects millions of people worldwide, with women making up almost two thirds of Alzheimer’s disease cases, the main form of dementia.
As populations age, understanding how sex‑specific factors influence dementia risk is increasingly important.
“In addition to living longer, the reason behind the higher female prevalence is thought to be related to the effects of menopause on brain metabolism and the impact of the main genetic risk factor APOE4 being greater in women.
“We wanted to better understand how HRT could prevent dementia and to assess if particular groups of women may respond differently.”
The findings offer a strong biological rationale for moving towards personalised prescribing strategies based on a woman’s surgical history, lifetime hormone exposure, and genetic profile.
This research was funded by the Biotechnology and Biological Sciences Research Council (BBSRC).
Dr Amanda Collis, Executive Director for Research Strategy and Programmes at BBSRC, said: “This study provides valuable new insights into how menopause and the timing of hormone replacement therapy may influence dementia risk in women.
“The findings suggest that HRT could have greater protective benefits for some groups, highlighting the potential for more personalised approaches to prevention.”
