Study Finds No Evidence That Hormone Therapy Use Affects Dementia Risk in Postmenopausal Women

There is no evidence that menopause hormone therapy (MHT) use either increases or decreases the risk of dementia in postmenopausal women, wrote authors of research published in The Lancet Healthy Longevity. Despite the findings, the authors recommend that further research be conducted to better clarify the role of MHT and dementia risk, particularly with dose, administration route, timing, and other characteristics.¹

Prior to this study, the use of MHT to treat menopausal symptoms in women and its associated effect on cognition and dementia were an area of public and clinical debate, primarily because of potential adverse effects (AEs) and conflicting evidence. In December 2024, investigators conducted an umbrella review to identify recent, high-quality systematic reviews on the association between MHT and risk of mild cognitive impairment or dementia in perimenopausal or postmenopausal women, including those with premature ovarian insufficiency or early menopause, with or without mild cognitive impairment.¹

According to the investigators, none of the existing systematic reviews met the “breadth and methodological rigor required for GRADE [Grading of Recommendations Assessment, Development, and Evaluation] methodology,” and evidence regarding MHT use and mild cognitive impairment or dementia following premature ovarian insufficiency or early menopause was particularly scarce. Additionally, there were no existing reviews that evaluated the use of testosterone, and generally, the papers relied heavily on low-quality observational studies.¹

Lead author Melissa Melville, a PhD student at University College London, said, “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. MHT is widely used to manage menopausal symptoms, yet its impact on memory, cognition, and dementia risk remains one of the most debated issues in women's health. Conflicting research and concerns about potential harms have fueled public and clinical debate, leaving women and clinicians unsure whether MHT might raise or reduce their risk of dementia.”²

For this review, the investigators searched MEDLINE via Ovid, Embase via Elsevier, Cochrane via Ovid, and PsycINFO via Ovid for systematic reviews published between January 1, 2000, and Dec 19, 2024. Because no existing review met their quality or scope criteria, they instead conducted a systematic review and meta-analysis of primary studies published from January 1, 2000, to October 20, 2025. Eligible primary studies included randomized controlled trials (RCTs), nonrandomized intervention studies, and prospective observational studies that examined the association between MHT—including estrogen-only MHT, combined MHT, testosterone, and tibolone—and incident mild cognitive impairment or dementia.¹

A total of 5914 records were gathered. Among these papers, 10 studies (1 RCT, 9 observational studies) with a total of 1,016,055 participants were included. In these papers, certainty of evidence ranged from moderate to very low. No included studies examined testosterone or its use in premature ovarian insufficiency.¹

The authors determined that, based on available data, there is no evidence that MHT has a positive, negative, or null effect on the risk of dementia or mild cognitive impairment. They wrote that this finding is consistent with previous studies but extends this uncertainty to MHT and dementia following premature or early menopause. Further, the authors’ systematic review and meta-analysis confirmed there is no current evidence regarding the effect of testosterone on mild cognitive impairment or dementia.¹

The only RCT of MHT and dementia reported an increased risk with both estrogen-only MHT (HR 1.49 [95% CI 0.83–2.66]) and combined MHT (HR 1.76 [95% CI 1.19–2·60]) in women aged 65 years and older initiating MHT. However, the wide confidence intervals for estrogen-only MHT indicate “serious imprecision.” In addition, the observational studies reported inconsistent associations, with very low certainty because of bias, heterogeneity, and imprecision. Timing of initiation and duration of use showed mixed and uncertain results. Overall, available evidence to date does not support MHT solely for risk reduction of dementia, nor does MHT increase dementia risk.¹

“This review is the most comprehensive and methodologically rigorous synthesis to date of RCT and observational evidence on MHT and mild cognitive impairment or dementia risk, stratified by formulation, age at initiation, and duration of use. By focusing on higher-quality studies, we provide more precise pooled estimates and a transparent assessment of certainty using GRADE. We found that MHT neither increases nor decreases [the] risk of mild cognitive impairment or dementia in postmenopausal women.”

Senior author Aimee Spector, PhD, said, “Currently, the World Health Organization (WHO) provides no guidance on menopause hormone therapy and cognitive outcomes, leaving a critical gap for clinicians and policymakers. To cut through the noise, we reviewed the most rigorous research there is on the subject and found that MHT does not appear to impact dementia risk either positively or negatively. This review will help to inform the upcoming WHO guidelines on reducing the risk of cognitive decline and dementia, which are expected to be released in 2026. More high-quality, long-term research is still needed to fully understand the long-term impacts of menopausal hormone therapy.”²

REFERENCES

1. Melville M, He L, Desai R, et al. Menopause hormone therapy and risk of mild cognitive impairment or dementia: a systematic review and meta-analysis. The Lancet Healthy Longevity. 2025;6(12):100803. doi:10.1016/j.lanhl.2025.100803

2. University College London. Menopause hormone therapy does not appear to impact dementia risk. News release. December 22, 2025. Accessed January 21, 2026. https://www.eurekalert.org/news-releases/1110717