A recent meta-analysis commissioned by the World Health Organisation (WHO), which included health data from more than 1m women, found that hormone replacement therapy had no effect on dementia risk: it neither increased nor decreased it, according to the researchers.
The study was published in The Lancet Healthy Longevity.
“The WHO currently provides no guidance on HRT (or menopause hormone therapy – MHT) as it’s now being called) and dementia risk, leaving a critical gap for women, clinicians and policymakers. Our work will help inform upcoming WHO guidelines on reducing the risk of cognitive decline and dementia,” Melissa Melville, a PhD Candidate and Ageing Researcher in the Department of Clinical Health Psychology at University College London and first author of the study, told Healthline.
Melville stressed that the work’s importance is twofold: for clinicians, there is an urgent need for higher-quality research; for patients, decisions about the therapy should be guided by symptoms and well-established benefits and risks.
Complicated history
While MHT began in the 1960s and peaked in the United States in the 1990s, in 2002, results from the Women’s Health Initiative (WHI), the first and only large randomised controlled trial of MHT, suggested that the risks outweighed the benefits.
Participants in the study had an increased risk of breast cancer, stroke, pulmonary embolism and heart attack. After publication of these results, MHT therapy declined by 45%.
A subgroup study – the Women’s Health Initiative Memory Study (WHIMS) – later published findings on dementia and Alzheimer’s disease among women taking MHT. The study reported a substantially increased risk of dementia and overall cognitive decline.
That study alone effectively cemented the perception that MHT increased dementia risk and had a chilling effect on both patient use and subsequent research.
“A lot of other research was halted at that point, which led to only really having this study as our data point for many years. That’s what happens when a landmark paper suggests that we’re doing something potentially unsafe,” said Caroline Just, MD, programme lead for women’s neurology and neuro-obstetrics at the Cleveland Clinic. Just wasn’t involved in the study.
Despite its outsized and decades-long impact on women’s health, experts say the WHI’s methodology, and even the types of hormones used, are a far cry from modern practice.
“(The WHI) is not reflective of our practice patterns now, nor the hormone therapy regimens we’re using now,” said Karen Adams, MD, Farwell Family Director of the Stanford Programme in Menopause & Healthy Ageing at Stanford Medicine, who wasn’t involved in the research.
WHIMS remains the only randomised controlled trial to examine hormone therapy and dementia risk. Most other studies have been observational and therefore more susceptible to bias. Of the 10 studies reviewed in the new meta-analysis, nine were observational.
Over the years since WHIMS was published, evidence of the association between MHT has been conflicting, with some studies also concluding that it increases the risk of dementia, while others suggest that it may be protective against cognitive decline.
The new review suggests that neither is true.
“When you put all the data together, as is common when something shows one way and other studies show the other way, the effects cancel out. So, there was no convincing difference in terms of protection or increased risk from menopause hormone therapy,” Just said.
“The depth of this review is extremely reassuring to people who prescribe menopause hormone therapy,” she added.
Adams emphasised the limitations of current evidence.
“We just don’t have good studies,” she told Healthline. “The best thing we can say right now based on the data we have is that hormone therapy probably does not increase the risk of dementia, but it probably doesn’t prevent it either.”
Women’s dementia risk
Women are disproportionately affected by dementia, even after accounting for their longer life expectancy. Almost two-thirds of Americans with Alzheimer’s disease, the most common cause of dementia, are women.
Given that disparity, it is understandable to be concerned about ways to reduce this risk, but for now, the available evidence suggests MHT is not one of those risk factors.
The apparently neutral effects of MHT on dementia risk suggest one clear takeaway for patients: decisions about using the therapy should be guided by symptom relief and quality-of-life considerations, not fear.
“Dementia should not drive MHT decisions,” Melville said.
And Adams agreed. For women under 60 or within 10 years of their last menstrual period, there is a “window of opportunity” to start MHT, she pointed out.
“To the best of our knowledge, if you start at the right time, you can continue indefinitely without significant risk,” she added.
“Many cases of dementia are likely to be modifiable, meaning there’s something that the patients can do to alter or reduce their risk that is not genetic,” Just said.
Study details
Menopause hormone therapy and risk of mild cognitive impairment or dementia: a systematic review and meta-analysis
Melissa Melville, Lexi He, Roopal Desai, et al.
Published in The Lancet in December 2025
Summary
Background
Globally, dementia disproportionately affects women. Changes in circulating sex steroids over the menopause transition might contribute to this sex difference. Menopause hormone therapy (MHT) is recommended by the UK National Institute for Health and Care Excellence to manage menopausal symptoms, but whether MHT use affects dementia risk and how this association might vary by age at menopause is unclear. We aimed to assess whether MHT (vs no MHT) affects the risk of mild cognitive impairment or dementia in peri-menopausal or post-menopausal women, including those with premature ovarian insufficiency or early menopause (with normal cognition or mild cognitive impairment), and whether MHT type, duration, or age at initiation influence this risk.
Methods
We systematically searched MEDLINE via OVID, Embase via Elsevier, Cochrane via OVID, and PsycINFO via OVID for systematic reviews published between 1 January 2000, and 19 December 2024. As no existing review met our quality or scope criteria, we proceeded to conduct a systematic review and meta-analysis of primary studies published from 1 January 2000 to 20 October 2025. Eligible primary studies included randomised controlled trials (RCTs), non-randomised intervention studies, and prospective observational studies examining the association between MHT—including oestrogen-only MHT, combined MHT, testosterone, and tibolone—and incident mild cognitive impairment or dementia. Two reviewers independently screened studies, extracted data, and assessed risk of bias using RoB 2 and ROBINS-E, with certainty of evidence rated using GRADE. Meta-analyses pooled relative risk estimates in a random-effects model. The protocol was preregistered on PROSPERO (CRD42025639384).
Findings
Of 5 914 records, 10 studies (one RCT and nine observational studies) with a total of 1 016 055 participants were included. Certainty of evidence ranged from moderate to very low. No included studies examined testosterone or use in premature ovarian insufficiency. No significant association was found between MHT use and risk of mild cognitive impairment or dementia. Subgroup analyses by timing, duration, and type of MHT showed no significant effects.
Interpretation
This review found no evidence that MHT use either increases or decreases the risk of dementia in post-menopausal women. This reinforces current clinical guidance, that MHT prescription should be based on other perceived benefits and risks and not for dementia prevention. High-quality, long-term studies are needed to clarify the role of MHT and dementia risk, particularly regarding formulation, dose, route, timing, and duration of treatment, with a focus on women with premature ovarian insufficiency, early menopause, or mild cognitive impairment.
See more from MedicalBrief archives:
Suggested link between HRT and dementia – Danish study
Early menopause may raise dementia risk later – UK study of 150,000 women
Hormone therapy associated with improved cognition
HRT not linked to increased risk of dementia — Largest study yet