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

BMJ. 2021 Sep 29:374:n2182. doi: 10.1136/bmj.n2182.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / chemically induced*
  • Alzheimer Disease / epidemiology
  • Case-Control Studies
  • Databases, Factual
  • Dementia / chemically induced*
  • Dementia / epidemiology
  • Estrogen Replacement Therapy / adverse effects*
  • Estrogen Replacement Therapy / methods
  • Estrogens / adverse effects
  • Female
  • Humans
  • Middle Aged
  • Odds Ratio
  • Postmenopause / drug effects*
  • Postmenopause / psychology*
  • Progestins / adverse effects
  • Risk Factors
  • United Kingdom / epidemiology


  • Estrogens
  • Progestins