Menopausal hormone therapy not associated with increased dementia risk

The findings of this retrospective study in the United Kingdom should reassure women taking menopausal hormonal therapy but do not support its use to prevent dementia, a linked opinion piece said.

Menopausal hormone therapy (MHT), also known as hormone replacement therapy, was not associated with an increased risk for dementia, a large British study concluded.

Researchers used two British primary care databases to analyze prescriptions for 118,501 women ages 55 years and older who were diagnosed with dementia between 1998 and 2020 and 497,416 women matched by age and general practice but with no history of dementia. Information from prescriptions issued more than three years before the case diagnosis included hormone type, dose, and method of administration. Other relevant factors, such as family history, smoking, alcohol consumption, pre-existing conditions, and other prescribed drugs, were also analyzed. Results were published by The BMJ on Sept. 30.

Overall, 16,291 (14%) dementia patients and 68,726 (14%) controls had used MHT up to three years previously. 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. Cases and controls younger than age 80 years who had been taking estrogen-only therapy for 10 years or more had a decreased global risk for dementia (adjusted odds ratio [aOR], 0.85; 95% CI, 0.76 to 0.94). Increased risk for Alzheimer's disease was seen among women who had used estrogen-progestogen therapy for between five and nine years (aOR, 1.11; 95% CI, 1.04 to 1.20) and for 10 years or more (aOR, 1.19; 95% CI, 1.06 to 1.33). This was equivalent to, respectively, five and seven extra cases per 10,000 woman-years, the authors calculated.

The study was observational and recording of menopausal symptoms was incomplete, particularly for women who registered after menopause, the authors noted. However, the study used a large data sample from primary care records and was designed to not only 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, they said.

The study's results should not change the recommendation against using MHT to prevent future dementia, a linked opinion piece stated. “At the same time, it is helpful for providers to put dementia findings in context for patients. No increase in risk of dementia was observed with oestrogen alone in this case-control study, and, for oestrogen plus progestogen, the increased risk was five to seven extra cases per 10 000 woman years,” the opinion authors wrote. “The primary indication for hormone therapy continues to be the treatment of vasomotor symptoms, and the current study should provide reassurance for women and their providers when treatment is prescribed for that reason.”