Melville, Melissa;
He, Lexi;
Desai, Roopal;
Nyamayaro, Primrose;
Fox, Chris;
Kothari, Kavita U;
Condron, Patrick;
... Spector, Aimee; + view all
(2025)
Menopause hormone therapy and risk of mild cognitive
impairment or dementia: a systematic review and
meta-analysis.
The Lancet Healthy Longevity
, 6
(12)
, Article 100803. 10.1016/j.lanhl.2025.100803.
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Abstract
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 Jan 1, 2000, and Dec 19, 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 Jan 1, 2000, to Oct 20, 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 5914 records, ten 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. / / Funding: The Public Health Agency of Canada.
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