Hormone Therapy is not linked to an Increased Risk of Dementia

There is some evidence that HRT may even increase the risk of dementia. Clinical trials examining the use of HRT to treat rather than prevent Alzheimer’s disease in women found no benefit in cognition. Hormone therapy is not associated with an increased risk of developing dementia, according to a study.

Menopausal hormone therapy (MHT, also known as hormone replacement therapy, HRT) is not associated with an increased risk of dementia, according to new research led by experts at the University of Nottingham.

The study, led by Dr. Yana Vinogradova from the University’s School of Medicine and published today in the BMJ, provides the most comprehensive and reliable risk estimates to date, and the findings should reassure women who require MHT. This is true regardless of hormone type, dose, or duration of use, according to a large UK study based on clinical records of women representative of the general population over many years.

New research shows that the use of menopausal hormone therapy (MHT – also known as hormone replacement therapy, HRT) is not linked to an increased risk of developing dementia.

Only in the subgroup of women with a specific Alzheimer’s disease diagnosis was a small increased risk association found for use of oestrogen-progestogen treatments, but this was only measurable after five years or more of use.

MHT alleviates symptoms such as hot flushes, sleep disturbance, mood swings, memory loss, and depression that many women experience during menopause. Some symptoms are similar to the early stages of dementia, and findings from laboratory studies and small trials suggest a possible beneficial link between oestrogen and age-related brain decline.

The Women’s Health Initiative Memory Study, on the other hand, found an increased risk of dementia in users of combined oestrogen-progestogen treatments, and a recent large Finnish study in Finland found a higher risk of developing Alzheimer’s disease in users of oestrogen-only therapy as well as users of combined treatments. Existing studies all had a number of flaws, including small sample sizes, a short time span for which data was available, limitations in the range of treatments covered, and methodological issues.

Hormone therapy not associated with an increased risk of developing dementia

Researchers from the Universities of Nottingham, Oxford, and Southampton devised a study that made use of two of the UK’s largest primary care databases (QResearch and CPRD). These keep track of diagnoses and prescriptions, and they have links to hospital records and other data collections. This enabled the researchers to investigate in depth the dementia outcomes for women who received any of the MHT treatments commonly prescribed by the UK National Health Service over a long period of time.

The study included 118,501 women aged 55 and older who were diagnosed with dementia between 1998 and 2020 (cases) and 497,416 women who were matched by age and general practice but did not have dementia records (controls). Details of hormone type, dose, and method of administration were extracted from MHT prescriptions written more than three years before the case diagnosis. Other relevant factors considered in the analysis included family history, smoking, alcohol consumption, pre-existing conditions (comorbidities), and other prescribed drugs. During the study period, 16,291 (14%) cases and 68,726 (14%) controls were exposed to MHT.

After controlling for all possible confounding factors, the study found no overall associations between MHT use and the risk of developing dementia. These findings were consistent across all treatments and application methods (pills, patches, creams, or devices), and were unaffected by dose or treatment duration. In line with biological studies, the researchers found a slightly lower risk of dementia in the subgroup of cases diagnosed younger than 80 years who had been on oestrogen-only therapy for 10 years or more.

The researchers acknowledge that some limitations in their data, such as incomplete recording of menopausal symptoms, particularly for women registered after menopause, may have influenced their findings. They do say, however, that this study, which is based on ‘real world’ data from the general population, “brings clarity to previously inconsistent findings and should reassure women in need of menopausal hormonal therapy.”

According to the researchers, “this study provides the most detailed estimates of risk for individual treatments, and results are consistent with existing guidelines about long-term exposures to combined hormone therapy treatments.”

Dr. Vinogradova stated: “We are pleased to be able to share findings that will reassure women in need of menopausal hormone therapy and facilitate discussions between doctors and patients about the safest treatments. We hope that they will be useful to other health professionals and policymakers as well.” The NIHR SPCR funded the research.