HRT linked to lower dementia risk in some women

Hormone replacement therapy (HRT) may reduce the risk of dementia — particularly for certain groups of women — according to a study from the University of East Anglia (UEA) and the University of Exeter. The researchers followed more than 180,000 postmenopausal women in the UK in what is believed to be the largest study of its kind, with their results published in the journal Alzheimer’s and Dementia.

“Dementia affects millions of people worldwide, with women making up almost two-thirds of Alzheimer’s disease cases, the main form of dementia,” said study leader Professor Anne-Marie Minihane, from UEA’s Norwich Medical School and Director of the Norwich Institute for Healthy Ageing at UEA.

“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 researchers analysed health data from the UK Biobank, tracking 183,450 postmenopausal women over an average follow-up period of 13.3 years. During that time, almost 4000 cases of dementia were identified.

The study examined whether using HRT for at least one year was associated with the risk of developing dementia, and whether that relationship varied depending on biological and genetic factors. The team also took into account other factors that could influence dementia risk and HRT use, such as age, socio-economic factors, other health issues and medication use.

Women who had used HRT had a 16% lower risk of developing Alzheimer’s — the main form of dementia — compared with those who had never used it. The greatest reduction was seen in women who had undergone surgical menopause — such as having their ovaries removed — with a 26% lower risk of developing any type of dementia compared with non-users.

The study also found that women who naturally had lower lifetime oestrogen exposure, due to starting their periods late or early menopause, seemed to benefit more from HRT, with a 16% lower risk of any type of dementia. Furthermore, the associations between HRT use and dementia were stronger in women who carry the APOE4 gene variant.

“This is really important,” Minihane said, “because APOE4 carriers are typically considered at higher risk and have fewer established prevention options.”

The age at which women started hormone therapy also appeared to influence outcomes. Those who began HRT between the ages of 46 and 56 experienced the greatest reduction in dementia risk.

This supports the so-called ‘critical window’ hypothesis, which suggests that hormone therapy may be more beneficial when initiated 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 this age range, reinforcing the importance of timing in hormone-based interventions.

This research builds on a previous study from UEA, which found that HRT use is associated with better memory, cognition and larger brain volumes in later life among women carrying the APOE4 gene. The team say their latest results provide a foundation for more personalised approaches to HRT prescribing — taking into account menopause type, genetic risk, lifetime hormone exposure and age at initiation.

“These findings represent a significant step forward,” said Professor David Llewellyn, from the University of Exeter Medical School. “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.”

Image credit: iStock.com/Zinkevych