HRT linked to lower dementia risk, large UK study finds

HRT use was linked to a lower dementia risk among postmenopausal women in a large UK study involving more than 180,000 participants.

Women who had used hormone replacement therapy (HRT) had a 16 per cent lower risk of developing Alzheimer’s disease than women who had never used it.

The strongest association was among women who had undergone surgical menopause. HRT users had a 26 per cent lower risk of developing any type of dementia than non-users.

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.”

Researchers from the University of East Anglia and the University of Exeter analysed health data from 183,450 postmenopausal women in the UK Biobank over an average follow-up period of 13.3 years.

Almost 4,000 cases of dementia were identified during that period.

The researchers looked at whether using HRT for at least one year was associated with dementia risk and whether that relationship differed according to biological and genetic factors.

They also accounted for factors that could influence dementia risk or HRT use, including age, socio-economic factors, other health conditions and medication use.

Women with naturally lower lifetime exposure to oestrogen, because they started their periods late or experienced early menopause, appeared to benefit more from HRT. Their risk of any type of dementia was 16 per cent lower than among non-users.

The associations between HRT use and dementia were also stronger among women carrying the APOE4 gene variant, a known risk factor for Alzheimer’s disease.

The age at which women began HRT also appeared to be linked to outcomes. Women who started treatment between the ages of 46 and 56 had the greatest reduction in dementia risk.

Researchers said this was consistent with the “critical window” hypothesis, which suggests hormone therapy may be more beneficial when started closer to the menopausal transition rather than later in life.

The study did not find the same level of benefit when HRT was started outside that age range.

Minihane said: “Our findings contribute to growing evidence that hormone therapy’s effects on brain health are complex and influenced by individual biological factors.

“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.”

The findings build on previous research from UEA that found HRT use was associated with better memory, cognition and larger brain volumes in later life among women carrying APOE4.

The researchers said the latest results provide a foundation for more personalised approaches to HRT prescribing, taking into account menopause type, genetic risk, lifetime hormone exposure and age when treatment begins.

Professor David Llewellyn, of the University of Exeter Medical School, said: “These findings represent a significant step forward. Rather than asking simply whether HRT affects dementia risk, we’ve been able to identify which women are most likely to benefit, and when.

“That’s the foundation on which genuinely personalised approaches to women’s brain health can be built.”

The 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.”