Key takeaways
- A UCL-led review of more than 1 million women found no clear evidence that menopause hormone therapy (MHT) alters dementia risk.
- Findings support current guidelines that MHT should not be prescribed for dementia prevention.
- Evidence for both oestrogen-only and combined MHT showed very low certainty across most dementia and Alzheimer’s disease outcomes.
- Small signals of increased or decreased risk were observed in some analyses, but effects were trivial or inconsistent.
- Major evidence gaps remain for key subgroups, including women with early menopause, premature ovarian insufficiency, and non-oestrogen therapies.
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 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,” said Melissa Melville, 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.
Oestrogen-only MHT and dementia risk
There were 15 articles included in the final analysis, with assessed outcomes including all-cause dementia, Alzheimer’s Disease, and dementia or mild cognitive impairment. One of these studies found a potential increase in dementia risk from oestrogen-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 oestrogen-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’s disease, the pooled RR was 0.95 across 4 observational studies for oestrogen-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, a hazard ratio 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’s 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’s disease in patients with 5 years or less of oestrogen-only MHT, with a trivial effect included in the confidence interval. In those with 5 to 10 years of oestrogen-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 oestrogen-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 oestrogen-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
- Menopause hormone therapy does not appear to impact dementia risk. University College London. December 22, 2025. Accessed January 5, 2025. https://www.eurekalert.org/news-releases/1110717
- Melville M, He L, Desai R. Menopause hormone therapy and risk of mild cognitive impairment or dementia: a systematic review and meta-analysis. The Lancet Healthy Longevity. 2025;6(1). doi:10.1016/j.lanhl.2025.100803
