No evidence links menopause hormone therapy to dementia risk

Researchers from University College London (UCL) have found no evidence linking menopause hormone therapy (MHT) to increased or decreased dementia risk among post-menopausal women, publishing their findings in The Lancet Healthy Longevity.¹

The review was the most comprehensive synthesis of evidence about this topic recorded to date, with over 1 million participants providing data. Investigators concluded the results reinforce current guidelines that hormone replacement therapy (HRT) should be guided by perceived risks and benefits, not for dementia prevention.

“Across the globe, dementia disproportionately affects women, even after accounting for women’s longer life spans, 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,” said Melissa Melville, a PhD student at UCL Psychology & Language Sciences.

Cognitive health assessments

The systematic review and meta-analysis were conducted to evaluate the impact of MHT on mild cognitive impairment or dementia in perimenopausal and postmenopausal women.² Articles were obtained through systematic searches of the Embase, MEDLINE, PsycINFO, and Cochrane databases.

Studies published between January 1, 2000, and October 25, 2025, including perimenopausal or postmenopausal women, and reporting a quantitative association between MHT use and incident dementia or mild cognitive impairment were included. Women with premature ovarian insufficiency or early menopause were eligible for inclusion.

Data was extracted by 2 independent reviewers, with a third reviewer completing validation. These reviewers obtained data such as author details, year of publication, country of study, sample size, study design, participant demographics and baseline characteristics, intervention, comparator, outcomes, and measures of association.

Estrogen-only MHT and dementia risk

There were 15 articles included in the final analysis, with assessed outcomes including all-cause dementia, Alzheimer disease, and dementia or mild cognitive impairment. One of these studies found a potential increase in dementia risk from estrogen-only MHT in women aged at least 65 years, but this study had a low certainty of evidence.

When pooling 5 observation studies, the risk ratio (RR) for dementia risk following estrogen-only MHT was 1.10. While this indicated a potential slight increase in risk, the certainty was low because of bias, inconsistency, imprecision, and indirectness.

For Alzheimer disease, the pooled RR was 0.95 across 4 observational studies for estrogen-only MHT vs no MHT, indicating a possible slight decline in risk. Bias, imprecision, and substantial inconsistency caused certainty to be very low.

Combined MHT findings

In one randomized controlled trial, an HR of 1.76 was reported for probable dementia following combined MHT in women aged at least 65 years, with moderate certainty. The modest absolute difference indicated no significant change in dementia risk from combined MHT.

Combined MHT also had a pooled HR of 1.11 for Alzheimer disease across 5 observational studies, alongside an absolute difference of 23.87 additional cases per 1000 individuals. A trivial effect was noted for the confidence interval, and certainty was very low.

A pooled RR of 1.16 was reported for dementia or Alzheimer disease in patients with 5 years or less of estrogen-only MHT, with a trivial effect included in the confidence interval. In those with 5 to 10 years of estrogen-only MHT, the pooled RR was also 1.16.

Evidence gaps and future research needs

Finally, the pooled RR was 0.93 for more than 10 years of estrogen-only MHT. All cases had very low certainty. Additionally, very low certainty was reported for risks identified based on the age when initiating MHT.

These risks included a pooled RR of 1.12 when initiating estrogen-only MHT when aged 45 to 55 years, vs 1.08 when aged more than 60 years. Overall, the data highlighted very low certainty of evidence for dementia risks associated with MHT.

“Although our search comprehensively searched for studies including premature ovarian insufficiency, early menopause, mild cognitive impairment, and testosterone, no eligible studies were identified specifically addressing these subgroups or interventions,” wrote investigators. “This highlights important gaps in the current evidence base, which limit evidence-based care for women.”

References

1. Menopause hormone therapy does not appear to impact dementia risk. News release. University College London. December 22, 2025. Accessed January 5, 2025. https://www.eurekalert.org/news-releases/1110717
2. Melville M, He L, Desai R. Menopause hormone therapy and risk of mild cognitive impairment or dementia: a systematic review and meta-analysis. Lancet Healthy Longev. 2025;6(12):100803. doi:10.1016/j.lanhl.2025.100803