Credit: LightField Studios on Shutterstock
A tenuous connection between hormone therapy and increased dementia risk was noted, but more research is warranted.
In A Nutshell
- A review of 10 studies including over 1 million women found no consistent link between menopause hormone therapy and dementia risk, but most evidence was rated as very low certainty.
- The only randomized trial found increased dementia risk when women started combined hormone therapy at age 65 or older, but this doesn’t reflect typical use, which begins during menopause in the late 40s or early 50s.
- Timing and duration of hormone therapy didn’t appear to change dementia risk, though wide confidence intervals mean smaller effects can’t be ruled out.
- No studies examined women with premature menopause (before age 40) or testosterone therapy, leaving major gaps in understanding hormone therapy’s effects on brain health.
For decades, women facing menopause have received conflicting advice about hormone therapy and brain health. Some studies suggested it could ward off dementia. Others warned it might increase the risk. Now, a review analyzing data from more than one million women offers the clearest big-picture look so far, and it doesn’t show a consistent link either way.
The systematic review and meta-analysis, published in The Lancet Healthy Longevity, examined ten studies involving 1,016,055 participants to determine whether menopause hormone therapy affects the risk of developing mild cognitive impairment or dementia. Researchers found no significant association between hormone therapy use and dementia risk. Still, many results were low-certainty and wide-ranging, so smaller effects (good or bad) can’t be fully ruled out. The research challenges both the hope that hormone therapy might protect aging brains and the fear that it might harm them.
Dementia disproportionately affects women worldwide, even when accounting for longer life expectancy. Changes in sex hormone levels during menopause have long been suspected as a potential contributor to this gender gap, leading researchers to investigate whether replacing those hormones might reduce dementia risk. The new analysis shows that women and their doctors should base hormone therapy decisions on other factors, not brain health.
How Researchers Studied Menopause Hormone Therapy and Dementia
Researchers from University College London, the University of Melbourne, and other institutions searched medical databases for studies published between 2000 and 2025. They initially looked for existing systematic reviews but found none meeting their quality standards, so they analyzed primary studies directly. The team included one randomized controlled trial and nine observational studies that tracked women over time to see who developed dementia.
The single randomized trial was the Women’s Health Initiative Memory Study, which enrolled women aged 65 and older. This study found that combined hormone therapy (estrogen plus progestin) increased dementia risk in women who started at age 65 or older, and the absolute difference was about 7 additional cases per 1,000. Estrogen-only therapy increased the risk of mild cognitive impairment. However, participants in this trial started hormone therapy at age 65 or older, which doesn’t reflect typical clinical practice where women usually begin treatment around menopause in their late 40s or early 50s.
The nine observational studies followed much larger groups of women for longer periods, ranging from about 3 to 19 years. These studies examined both estrogen-only therapy (for women who had their uterus removed) and combined therapy (for women who still had their uterus). Researchers assessed each study for potential biases and rated the certainty of evidence using a standardized grading system.
What the Evidence Shows About Hormone Therapy and Dementia Risk
When researchers pooled data from five observational studies including 672,195 women, they found a pooled risk ratio of 1.10 for estrogen-only therapy and dementia. This translates to a possible slight increase of about 9 additional dementia cases per 1,000 women, but the confidence interval was wide enough to include both potential benefit and harm. For combined hormone therapy, four observational studies with 693,412 women showed a pooled risk ratio of 1.12, or about 10 additional cases per 1,000 women, again with confidence intervals spanning both directions.
Researchers examined whether timing mattered by analyzing women who started hormone therapy at different ages. Some theories proposed a “critical window” where starting hormones close to menopause might be protective, while starting later could be harmful. The data didn’t support this idea. Women who started therapy between ages 45 and 55 showed no clear difference in dementia risk compared to those who started at age 60 or older.
Duration of use also appeared to make little difference. Researchers looked at women who used hormone therapy for less than 5 years, 5 to 10 years, and more than 10 years. While one analysis of long-term estrogen-only use (more than 10 years) showed a pooled risk ratio of 0.93, hinting at a possible small reduction in risk, the evidence certainty was rated as very low due to potential biases and statistical uncertainty.
Why Certainty Remains Low Despite Large Numbers
Despite analyzing data from more than 1 million women, researchers rated the certainty of most results as “very low,” with only one analysis rated as “moderate certainty.” Several factors contributed to this uncertainty. Observational studies, which made up most of the evidence, are vulnerable to confounding factors (women who choose to take hormone therapy may differ from those who don’t in ways that affect dementia risk independently of the hormones themselves).
Most studies relied on prescription records or self-reported hormone use without confirming whether women actually took their medications as prescribed. Dementia diagnoses often came from administrative health records rather than specialist evaluations, potentially missing or misclassifying cases. Studies also varied considerably in their designs, the populations they studied, and how they measured outcomes, making it challenging to combine results meaningfully.
Important gaps in the research became apparent. No studies examined testosterone therapy, despite some women using it for menopausal symptoms. The authors also point out that 2024 ESHRE guidance recommends MHT after premature ovarian insufficiency for dementia prevention, but they found no direct studies in that group. The evidence also lacked sufficient data on different delivery methods (pills versus patches, for example), specific types of estrogen or progestin, or dosage effects.
These results support current clinical guidance from organizations like the UK National Institute for Health and Care Excellence, which advises against prescribing hormone therapy specifically for dementia prevention. Women experiencing troublesome menopausal symptoms like hot flashes, night sweats, or vaginal dryness can still consider hormone therapy to address those issues. There’s no strong evidence it raises dementia risk overall, but the data aren’t perfect, so it’s smart to make the decision based on symptom relief and the usual medical tradeoffs.
The research team noted that future studies should focus on long-term, high-quality trials that examine specific formulations, doses, delivery routes, timing of initiation, and duration of treatment. Particular attention needs to go to understudied groups, including women with premature ovarian insufficiency, early menopause, or existing mild cognitive impairment. Until such studies exist, the relationship between hormone therapy and brain health remains uncertain rather than clearly beneficial or harmful.
Disclaimer: This article reports on published scientific research and is intended for informational purposes only. It is not medical advice. Women considering menopause hormone therapy should consult with their healthcare provider about their individual circumstances, symptoms, and the full range of potential benefits and risks. Treatment decisions should be made in partnership with a qualified medical professional who can assess personal health history and needs.
Paper Notes
Limitations
Researchers identified several important limitations. Only one randomized controlled trial was available, and it studied women who started hormone therapy at age 65 or older, which doesn’t reflect typical clinical practice. This trial was terminated early due to increased risks of non-cognitive adverse events, and high dropout rates (38-54%) exceeded projections. Most evidence came from observational studies susceptible to residual confounding, survival bias, and exposure or outcome misclassification. Hormone therapy use was often defined through prescription or self-reported data without confirmation of adherence, and dementia diagnoses were frequently based on administrative coding without specialist verification. Considerable heterogeneity existed in study design, exposure definitions, outcomes, and outcome ascertainment, limiting comparability. No studies examined testosterone or use in premature ovarian insufficiency. Insufficient data prevented evaluation of whether delivery method, type of estrogen, progestogen or progesterone, or dose modifies risk. Evidence gaps remain for women from ethnic minority backgrounds and those with pre-existing mild cognitive impairment. Potential modifying effects of genetic factors such as APOE ε4 status were not examined. Adverse events were not reported in observational studies.
Funding and Disclosures
This work was commissioned as part of the update of the 2019 WHO guidelines on risk reduction of cognitive decline and dementia. The ongoing update of the guidelines is funded by The Public Health Agency of Canada. The updated guidelines are expected to be released in 2026. Martha Hickey reports funding from the National Health and Medical Research Fund of Australia, Medical Research Future Fund of Australia, Wellcome LEAP, The National Institute for Health and Care Research and meeting support from UK NICE, membership of a WHO international advisory board, board membership of BreastScreen Victoria, and an editor role at Cochrane Collaboration. All other authors declared no competing interests.
Publication Details
Authors: Melissa Melville, Lexi He, Roopal Desai, Primrose Nyamayaro, Chris Fox, Kavita U Kothari, Patrick Condron, Miao Miao, Martha Hickey, Aimee Spector
Journal: The Lancet Healthy Longevity | Title: Menopause hormone therapy and risk of mild cognitive impairment or dementia: a systematic review and meta-analysis | DOI: 10.1016/j.lanhl.2025.100803 | Published: December 22, 2025 (published online)
Affiliations: Department of Clinical, Educational and Health Psychology, University College London, London, UK; Research and Development Department, North East London NHS Foundation Trust Goodmayes Hospital, Ilford, UK; Global Brain Health Institute Trinity College Dublin, Dublin, Ireland; Exeter Medical School, University of Exeter, Exeter, UK; Department of Obstetrics, Gynaecology and Newborn Health, University of Melbourne and the Royal Women’s Hospital, Melbourne, VIC, Australia; and other institutions.
