Menopausal hormone therapy may lower dementia risk, study suggests

Women using menopausal hormone therapy had a lower dementia risk, with oestrogen-only users showing fewer Alzheimer’s-related brain changes in a recent study.

Researchers stressed that the findings do not show that hormone therapy prevents dementia, but found women using oestrogen-only treatment had fewer biological signs linked to Alzheimer’s disease.

The observational study also found that women using this form of hormone therapy were less likely to receive a clinical dementia diagnosis.

The study combined clinical data with biomarkers and evidence from brain tissue collected after death to build a more detailed picture of the relationship between hormone therapy and Alzheimer’s-related changes.

The findings contrast with several previous studies reporting that menopausal hormone therapy increases dementia risk.

Dr Hadi Hosseini, associate professor of psychiatry and behavioural sciences at Stanford University in the US and senior author, said: “Our study is unique in that we looked at all the standards of Alzheimer’s diagnosis, including the gold-standard outcome: Alzheimer’s-associated hallmarks in autopsied brains.”

Hosseini said many conditions can affect memory and that clinical diagnoses are not always accurate. Examining brain tissue allows researchers to look directly for the defining biological features associated with Alzheimer’s disease.

Researchers examined medical records from 21,462 women taking part in two large US studies.

They looked only at women who used oestrogen-only therapy because previous studies indicated that treatment combining oestrogen and progestin may increase dementia risk.

This group was compared with women who reported no use of menopausal hormone therapy.

The records included data from 258 brain autopsies of women who had reported using oestrogen-only menopausal hormone therapy and 2,701 autopsies from women who had not used hormone therapy.

After adjusting for factors including age, women who took hormone therapy had a 35 per cent lower chance of showing biological signs of Alzheimer’s disease than those who did not use hormone therapy.

Hormone therapy use was also associated with a 39 per cent lower risk of receiving a clinical dementia diagnosis and a reduced risk of memory problems or declining functional abilities.

Dr Tom Blackmore, research programmes manager at Alzheimer’s Research UK, said: “Dementia has been the leading cause of death for women in the UK for over a decade, yet we still don’t fully understand why women are more likely to be affected by the condition than men.

“Understanding how hormones, menopause and ageing influence brain health is an important area of dementia research.

“While these findings are interesting, this study can only show an association and cannot tell us whether hormone therapy itself reduced dementia risk.

“Many factors influence a person’s likelihood of developing dementia, and women who received hormone therapy may differ from those who did not in ways that also affect their long-term brain health.”

In current standard practice, oestrogen-only therapy is prescribed to people who have undergone a hysterectomy because of the increased risk of endometrial cancer.

Blackmore also said the study focused exclusively on women taking oestrogen-only hormone therapy, which “differs substantially from how hormone replacement therapy is typically used today.”

Although early studies suggested menopausal hormone therapy might help protect menopausal women from dementia, later research produced inconclusive results.

A large analysis published in 2003 suggested the opposite, finding that oestrogen-plus-progestin formulations appeared to increase dementia risk, particularly when started at an older age.

Hosseini said: “There have been a lot of conflicting findings about MHT’s [menopausal hormone therapy’s] effects on Alzheimer’s disease outcomes.”

He added: “Different studies may have involved different age ranges of initiating MHT.”

Hosseini said studies may also have examined different clinical outcomes and biomarkers, combined different hormone therapy formulations or looked at different routes of administration and treatment durations.

Blackmore added that the findings “are not a reason for women to start or stop hormone replacement therapy with the aim of reducing dementia risk.”

He added: “Instead, the study provides valuable clues about the biology underlying dementia and highlights the need for more research into women’s brain health.

“Larger and more diverse studies will be needed to determine whether hormone-based treatments could play any role in reducing dementia risk.”

According to Alzheimer’s Research UK, an estimated 982,000 people are living with dementia in the UK, with around 65 per cent of those affected being women.