Hormone replacement therapy not associated with an increased risk of developing dementia

A large UK study has found that hormone replacement therapy (HRT) is not associated with an increased risk of developing dementia, regardless of hormone type, dose, or duration.

The study, which was published in the British Medical Journal (BMJ), aimed to address the uncertainty of whether using HRT could increase the risk of developing dementia as some studies have previously suggested.

Further reading:

• A women’s health agenda (Part 1)
• Older women’s health: the big issues (Part 2)

Researchers at the Universities of Nottingham, Oxford and Southampton used two primary care databases (QResearch and CPRD) to analyse HRT prescriptions for the 118,501 women aged 55 and older diagnosed with dementia between 1998 and 2020 (cases), and 497,416 women matched by age and general practice, but with no records for dementia (controls).

All information about HRT prescriptions issued more than three years before the cases diagnosis was used, including hormone type, dose and method of administration. Family history, smoking, alcohol consumption, comorbidities, additional prescribed drugs and other relevant factors were also taken into consideration.

Oestrogen-progestogen treatments found to slightly increase risk for small sub-group of women

Overall, 16,291 (14%) cases and 68,726 (14%) controls had been exposed to HRT in the period up to three years before diagnosis. The researchers adjusted for the full range of potentially confounding factors and found no overall associations between use of HRT and risk of dementia.

However, an analysis of cases with a specific diagnosis of Alzheimer’s disease showed a slight increase in risk associated with oestrogen-progestogen therapy. This rose gradually with each year of exposure, reaching an average 11% increased risk for use of between five and nine years and an average 19% for use of 10 years or more. This is the equivalent of five and seven extra cases per 10,000 women respectively.

Contrastingly, those who had been taking oestrogen only therapy for 10 years or more and were under the age of 80, were at a slightly decreased risk of dementia.

The findings should reassure women in need of HRT

The study is observational so cannot establish a cause, however, the researchers say the findings offer new, more reliable estimates about the risks associated with different types of menopausal therapy and the difference between component hormones.

They say that the study provides the most detailed estimates of risk for individual treatments, and their results are in line with existing concerns in guidelines about long-term exposures to combined hormone therapy treatments.

“The findings will be helpful to policy makers, doctors, and patients when making choices about hormone therapy,” they conclude.

In a linked opinion article, US researchers said that the observations do not change the recommendation that menopausal hormone therapy should not be used to prevent dementia, but should provide “reassurance for women and their providers” who are prescribed/prescribing HRT.