Hormone Replacement Therapy Linked to Reduced Dementia Risk in Large-Scale UK Study

New research suggests hormone replacement therapy (HRT) may be associated with a lower risk of developing dementia.

In the largest study of its kind, researchers tracked over 180,000 postmenopausal women in the UK. The results indicate that women who used HRT were 10% less likely to develop any form of dementia and 16% less likely to be diagnosed with Alzheimer’s disease—the most common type—compared to those who never used the treatment.

The most significant reduction appeared among women who had undergone surgical menopause; HRT users in this group showed a 26% lower risk of developing any type of dementia compared to non-users.

Professor Anne-Marie Minihane, director of the Norwich Institute for Healthy Ageing at the University of East Anglia and lead author of the study, stated: “While HRT has long been prescribed primarily to relieve menopausal symptoms such as hot flushes and night sweats, this work suggests it may also play a role in long‑term cognitive health for some women.”

Women face a higher lifetime risk of dementia than men, partly due to longer life expectancy. Researchers suggest this disparity may also stem from the effects of menopause on brain metabolism and the amplified impact of the primary Alzheimer’s risk gene, APOE4, in women.

Minihane added: “We wanted to better understand how HRT could prevent dementia and to assess if particular groups of women may respond differently.”

Drawing on data from the UK Biobank, the study monitored 183,450 postmenopausal women over an average period of 13 years, during which nearly 4,000 dementia cases were recorded. The team examined whether using any form of HRT for at least one year altered dementia risk.

Women with naturally lower lifetime estrogen exposure—due to late onset of menstruation or early menopause—appeared to benefit more from HRT, showing a 16% lower risk of any dementia type.

Genetics also influenced outcomes. The link between HRT use and reduced dementia risk was stronger in women carrying the APOE4 gene variant. “This is really important because APOE4 carriers are typically considered at higher risk and have fewer established prevention options,” Minihane noted.

The findings, published in the journal Alzheimer’s & Dementia, carry the caveat that they are based on observational data rather than a randomized controlled trial, meaning a causal relationship cannot be definitively proven.

For instance, HRT users in the study had a higher average education level than non-users. Although the analysis adjusted for socioeconomic factors, it remains possible that other differences between the groups influenced dementia risk.

Dr. Susan Kohlhaas, executive director of research and partnerships at Alzheimer’s Research UK, commented: “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.”

“Anyone considering starting or stopping HRT should speak to their GP about the potential benefits and risks for them.”

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