Use of menopausal hormone therapy and risk of dementia: nested case-control studies using QResearch and CPRD databases

Abstract

Objective To assess the risks of developing dementia associated with different types and durations of menopausal hormone therapy. Design Two nested case-control studies. Setting UK general practices contributing to QResearch or the Clinical Practice Research Datalink (CPRD), using all links to hospital, mortality, and social deprivation data. Participants 118 501 women aged 55 and older with a primary diagnosis of dementia between 1998 and 2020, matched by age, general practice, and index date to 497 416 female controls. Main outcome measures Dementia diagnoses from general practice, mortality, and hospital records; odds ratios for menopausal hormone treatments adjusted for demographics, smoking status, alcohol consumption, comorbidities, family history, and other prescribed drugs. Results Overall, 16 291 (14%) women with a diagnosis of dementia and 68 726 (14%) controls had used menopausal hormone therapy more than three years before the index date. Overall, no increased risks of developing dementia associated with menopausal hormone therapy were observed. A decreased global risk of dementia was found among cases and controls younger than 80 years who had been taking oestrogen-only therapy for 10 years or more (adjusted odds ratio 0.85, 95% confidence interval 0.76 to 0.94). Increased risks of developing specifically Alzheimer’s disease were found among women who had used oestrogen-progestogen therapy for between five and nine years (1.11, 1.04 to 1.20) and for 10 years or more (1.19, 1.06 to 1.33). This was equivalent to, respectively, five and seven extra cases per 10 000 woman years. Detailed risk associations for the specific progestogens studied are also provided. Conclusion This study gives estimates for risks of developing dementia and Alzheimer’s disease in women exposed to different types of menopausal hormone therapy for different durations and has shown no increased risks of developing dementia overall. It has shown a slightly increased risk of developing Alzheimer’s disease among long term users of oestrogen-progestogen therapies.

Reproductive factors and the risk of incident dementia: A cohort study of UK Biobank participants

“…Our study findings on HRT do not support associations between HRT and dementia risk, nor the aforementioned “timing hypothesis” for HRT initiation in relation to menopause for dementia risk. Consistently, a recent nested case–control study using a UK general practice cohort also found no evidence of an increased risk of dementia associated with menopausal hormone therapy; no evidence of different time of hormone therapy initiation may pose different risk of dementia [ 47 ].…”

The essential menopause curriculum for healthcare professionals: A European Menopause and Andropause Society (EMAS) position statement

“…Epidemiological evidence has been inconsistent with regard to risks of developing dementia. A study published in 2021 using a large data sample found that MHT use does not appear to increase the risk of developing dementia overall, but slightly increases the risk of developing Alzheimer's disease among long-term users of estrogenprogestogen therapies [38].…”

Impact of Caffeine on Alzheimer’s Disease Pathogenesis—Protective or Risk Factor?

“…The characterization and suppression of the most relevant risk factors for AD onset and evolution have also been important research directions, simultaneously with the extensive study of potential protective factors. Among the most studied protective factors with strong evidence for reducing the risk of AD we mention cognitive reserves [ 21 ], exercise [ 22 ], and administration of hormone therapy during the peri- and postmenopausal period [ 23 ]. Moreover, also other factors such as Mediterranean diet [ 24 ], coffee intake [ 25 ], and use of non-steroidal anti-inflammatory drugs (NSAID) [ 26 ] showed weak evidence and often contradictory results related to their influence on AD onset and evolution.…”