University of Southampton: Menopausal hormone therapy not linked to increased risk of developing dementia

Use of menopausal hormone therapy (MHT, also known as hormone replacement therapy, HRT) is not associated with an increased risk of developing dementia, regardless of hormone type, dose, or duration, concludes a large UK study.

Within the subgroup of women with a specific diagnosis for Alzheimer’s disease, a slight increasing risk association was found with use of oestrogen-progestogen treatments, but measurable only for long-term usage (5 years or more).

The researchers, led by the University of Nottingham and including Michael Moore, Primary of Primary Health Care Research at the University of Southampton, say this study “brings clarity to previously inconsistent findings and should reassure women in need of menopausal hormonal therapy.” The findings has been published in the BMJ.

MHT is used to relieve menopausal symptoms such as hot flushes, sleep disturbance, mood swings, memory losses and depression. Treatments include tablets containing oestrogen only, or a combination of oestrogen and progestogen, as well as patches, gels and creams.

Some menopausal symptoms are similar to early signs of dementia. Laboratory studies and small trials have suggested a beneficial link between oestrogen and age related brain decline. However, the largest trial of MHT, the Women’s Health Initiative Memory Study, found an increased risk of developing dementia among users of oestrogen-progestogen treatments.

To address this uncertainty, this new study set out to investigate the risks of developing dementia for women using any of the menopausal hormone therapy treatments commonly prescribed by the NHS.

The team used two UK primary care databases (QResearch and CPRD) to analyse MHT 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).

Overall, 16,291 (14%) cases and 68,726 (14%) controls had been exposed to menopausal hormone therapy in the period up to three years before diagnosis.

After adjusting for the full range of potentially confounding factors, the researchers found no overall associations between use of hormone therapy and risk of dementia, regardless of hormone type, application, dose, or duration of treatment.

This is an observational study, so cannot establish cause, and the researchers acknowledge some limitations, such as incomplete recording of menopausal symptoms, particularly for women registered after their menopause, that may have affected their results.

However, the study used a large data sample from primary care records and was designed not only to assess overall risk for women exposed to different types of long term hormone therapy but also to explore the differences between component hormones, offering new, more reliable estimates for doctors and their patients.

The researchers say this 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.

Study co-author Professor Moore said “Users of hormone therapy for menopause should be reassured by these findings that overall therapy was not associated with any increased risk of dementia clarifying inconsistent results in earlier research”

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