Menopause hormone therapy does not appear to impact dementia risk

A major review of prior research has found no evidence that menopause hormone therapy either increases or decreases dementia risk in post-menopausal women, in a new study led by University College London researchers and supported by the University of Exeter.

The findings, commissioned by the World Health Organisation (WHO) and published in The Lancet Healthy Longevity, add much-needed clarity to a hotly debated topic, and reinforce current clinical guidance that menopause hormone therapy, also called hormone replacement therapy or HRT, should be guided by perceived benefits and risks and not for dementia prevention.

Professor Chris Fox from the University of Exeter Medical School said: “The role of menopause hormone treatment and relationship to dementia is a worry for many women. But our state-of-the-art review indicates there is no evidence that menopause hormone treatment reduces or increases the risk of dementia. When deciding whether to take menopause hormone treatment, reducing one’s risk of dementia should not be part of that decision “

The new systematic review and meta-analysis is the most comprehensive and rigorous synthesis of evidence on menopause hormone therapy and dementia risk completed to date, including data from over one million participants.

The study publication follows a November announcement by the U.S. Food and Drug Administration (FDA) that it would remove the ‘black box’ warnings on menopause hormone therapy products. These warnings had previously included disproven claims about potential long-term health risks, including a claim of potential increased dementia risk. The FDA announcement further suggested that menopause hormone therapy might reduce the risk of Alzheimer’s disease, however, the findings of this latest review indicate that this claim is also not supported by the available evidence.

Lead author, PhD student Melissa Melville (UCL Psychology & Language Sciences), said: “Across the globe, dementia disproportionately affects women, even after accounting for women’s longer lifespans, so there’s a pressing need to understand what might be driving that risk, and to identify ways to reduce women’s risk of dementia.

“Menopause hormone therapy is widely used to manage menopausal symptoms, yet its impact on memory, cognition and dementia risk remains one of the most debated issues in women’s health. Conflicting research and concerns about potential harms have fuelled public and clinical debate, leaving women and clinicians unsure whether menopause hormone therapy might raise or reduce their risk of dementia.”

The international research team, based in the UK, Ireland, Switzerland, Australia and China, pulled together the best evidence on any potential links between menopause hormone therapy and dementia risk (including Alzheimer’s disease and other types of dementia), which included one randomised controlled trial and nine observational studies, with a total of 1,016,055 participants.

They found no significant association between menopause hormone therapy and the risk of dementia or mild cognitive impairment. Additional analyses of subgroups within the study participant pools, based on timing, duration and type of menopause hormone therapy, still did not reveal any significant effects. They found no evidence that menopause hormone therapy affected dementia risk after early menopause.

The researchers caution that their findings are limited by the scarcity of relevant randomised controlled trials, and that a lot of the evidence is of relatively low certainty. They say there remains a need for high-quality, long-term research, particularly in women from ethnic minority backgrounds or with early menopause, premature ovarian insufficiency, or mild cognitive impairment.

Senior author Professor Aimee Spector (UCL Psychology & Language Sciences) said: “Currently, the World Health Organisation provides no guidance on menopause hormone therapy and cognitive outcomes, leaving a critical gap for clinicians and policymakers. To cut through the noise, we reviewed the most rigorous research there is on the subject and found that menopause hormone therapy does not appear to impact dementia risk either positively or negatively.”

“This review will help to inform the upcoming WHO guidelines on reducing the risk of cognitive decline and dementia, which are expected to be released in 2026.

“More high-quality, long-term research is still needed to fully understand the long-term impacts of menopausal hormone therapy.”

The paper titled ‘Menopause Hormone Therapy and risk of mild cognitive impairment or dementia: a systematic review and meta-analysis’ is published in The Lancet Healthy Longevity.