Menopausal hormone therapy not linked to increased risk of developing dementia

Menopausal hormone therapy not linked to increased risk of developing dementia

Menopausal hormone therapy (MHT, also known as hormone replacement therapy, HRT) is not associated with an increased risk of developing dementia, regardless of the type, dose, or duration of the hormone used, according to a large UK study published today in The BMJ.

Within the subgroup of women with a specific diagnosis of Alzheimer's disease, there was a slight increasing risk associated with the use of oestrogen-progestogen treatments, but this association was only detectable after long-term use (5 years or more).

According to the researchers, this study "clarifies previously contradictory findings and should reassure women seeking menopausal hormonal therapy."

MHT is used to treat menopausal symptoms such as night sweats, insomnia, mood swings, memory loss, and depression. Tablets containing only oestrogen or a combination of oestrogen and progestogen are available, as are patches, gels, and creams.

Certain menopausal symptoms are comparable to early dementia symptoms. Laboratory and pilot studies have suggested a beneficial relationship between oestrogen and age-related cognitive decline. However, the Women's Health Initiative Memory Study, the largest trial of MHT, discovered an increased risk of developing dementia in users of oestrogen-progestogen treatments.

A large observational study conducted in Finland recently identified an increased risk of developing Alzheimer's disease among users of both oestrogen-only and oestrogen-progestogen treatments, but the study had some methodological flaws.

To address this uncertainty, researchers at the Universities of Nottingham, Oxford, and Southampton conducted a study to determine the risk of developing dementia in women who receive any of the menopausal hormone therapy treatments that are commonly prescribed in the UK National Health Service.

They analysed MHT prescriptions for 118,501 women aged 55 and older diagnosed with dementia between 1998 and 2020 (cases) and 497,416 women matched by age and general practise but without dementia records (controls).

All data from MHT prescriptions written more than three years prior to the case diagnosis, including the hormone type, dose, and method of administration, were analysed.

Additional relevant factors were considered in the analysis, including family history, smoking, alcohol consumption, pre-existing conditions (comorbidities), and other prescribed medications.

In total, 16,291 (14%) cases and 68,726 (14%) controls had been exposed to menopausal hormone therapy within the three years preceding diagnosis.

After adjusting for a wide variety of potentially confounding variables, the researchers discovered no overall association between hormone therapy use and dementia risk, regardless of the type of hormone, application, dose, or duration of treatment.

They discovered a slightly decreased risk of dementia in women younger than 80 years who had been on oestrogen-only therapy for ten years or more.

An analysis of cases with a specific diagnosis of Alzheimer's disease, however, revealed a slight increase in risk associated with oestrogen-progestogen therapy. This increased gradually with each year of exposure, reaching an average risk increase of 11% for use between 5 and 9 years and 19% for use of 10 years or more – equivalent to five and seven additional cases per 10,000 woman years, respectively.

As this is an observational study, no causal relationship can be established, and the researchers acknowledge some limitations, including insufficient documentation of menopausal symptoms, particularly in women registered after menopause, which may have influenced their findings.

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

According to the researchers, this study provides the most detailed risk estimates for individual treatments, and their findings corroborate existing guidelines regarding long-term exposure to combined hormone therapy treatments.

“The findings will aid policymakers, physicians, and patients in making informed decisions about hormone therapy,” they conclude.

In general, these findings do not alter the US researchers' recommendation that menopausal hormone therapy should not be used to prevent dementia, according to a linked opinion article. Simultaneously, it is beneficial for providers to contextualise dementia findings for patients, they add.

“The primary indication for hormone therapy remains the treatment of vasomotor symptoms, and this study should reassure women and their providers when treatment is prescribed for that purpose,” they conclude.