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Hormone replacement therapy (HRT) use is associated with a lower risk of dementia, a large-scale study has found.
Publishing their findings in Alzheimer’s and Dementia on 26 August 2026, researchers analysed data from 183,450 postmenopausal women in the UK Biobank, which included women who had taken HRT for at least one year compared with women who had never used HRT or used it for less than 12 months. The participants were assessed at 22 assessment centres in the UK between 2006 and 2010.
The study authors noted that age-standardised dementia rates are higher in women than in men, which suggests that female-specific factors may contribute to risk. However, evidence on the link between HRT use and cognitive outcomes or dementia risk was “conflicting and inconclusive”, they added.
The study results also revealed that initiation of HRT in women aged 46–56 years was associated with a 10% reduced risk of dementia.
For all-cause dementia, HRT was associated with a reduced risk with a hazard ratio of 0.90 (95% confidence interval [CI], 0.84–0.96; p = 0.001), the study results highlighted. However, they also showed that for women who had a natural menopause, the risk association was not statistically significant, with a hazard ratio of 0.94 (95% CI, 0.87–1.01; p = 0.091).
The study results underscored that for women who underwent surgical menopause, HRT was associated with a statistically significant reduction in dementia risk, with a hazard ratio of 0.74 (95% CI, 0.65–0.84; p < 0.001).
HRT was associated with reduced Alzheimer’s disease risk, with a hazard ratio of 0.84 (95% CI, 0.77–0.92; p < 0.001), the study results revealed. They also showed that for all-cause dementia, natural versus surgical menopause influenced the findings: for women who had a natural menopause, the hazard ratio was 0.89 (95% CI, 0.80–0.99; p = 0.03), while for those who had surgical menopause, the hazard ratio was 0.68 (95% CI, 0.56–0.82; p < 0.001).
The study authors said that the stronger associations for potential benefit of HRT in surgical vs. natural menopause “may in part reflect the HRT formulation”, adding that in natural menopause, a combined oestrogen–progestogen HRT is usually prescribed, along with progestogen for women with a functional uterus. In surgical menopause, oestrogen-only HRT formulations are usually prescribed, they said.
The study authors also noted that association does not necessary mean causation.
”HRT use is subject to selection (healthy-user) bias, as women who use HRT can differ systematically from non-users in characteristics that are also associated with dementia risk, including socioeconomic status, educational attainment, ethnicity and lifestyle factors,” they said.
Although, the study authors added that these factors were corrected for in the study, they could not eliminate the possibility that confounding factors remain. Randomised controlled trials would help to confirm associations and help tailor HRT according to risk factors, they added.
Ian Maidment, professor of clinical pharmacy at Aston University, commented: “Overall, HRT appeared to have a potential modest effect with the available evidence indicating less impact than physical activity.
“Limitations include lack of information on the type of HRT (e.g. oestrogen only or oestrogen combined with progesterone) and the dose,” he continued.
“We also need more research in diverse communities — the data mainly included women from more affluent areas and of European descent.”
Susan Kohlhaas, executive director of research and partnerships at Alzheimer’s Research UK, said: “This is a large and carefully conducted study with a long follow-up period. The researchers also carried out a range of additional analyses to test how robust their findings were, including accounting for other factors that could influence dementia risk.
“Following women from menopause for long enough to measure dementia outcomes in a randomised trial is challenging, so high-quality long-term studies like this have an important role in building our understanding of whether HRT use in midlife is associated with dementia risk many years later.
“This study alone isn’t enough to tell us whether HRT should be used to reduce dementia risk, but it provides further evidence that the timing of HRT and a woman’s hormonal history may matter. We now need research that can establish whether HRT itself is responsible for these differences in dementia risk and understand which forms of HRT may have an effect.”
