BACKGROUND AND PURPOSE:

• Pourhadi et al. (BMJ, 2023) assessed the association between use of menopausal hormone therapy and dementia

METHODS:

• Nationwide, nested case-control study
  • Danish national registries
• Participants
  • Danish women | 50 to 60 years on January 1, 2000
  • No history of dementia or contraindications for hormone therapy
  • Exclusion: Prior hysterectomy and bilateral oophorectomy
• Exposures
  • Menopausal hormone therapy
• Study design
  • Cases: Patients with dementia
  • Controls: Age-matched patients
• Primary outcome
  • All-cause dementia defined as
    • First-time diagnosis or
    • First-time use of dementia specific medication

RESULTS:

• Cases: 5589 | Controls: 55,890
• Estrogen-progestogen therapy was associated with increased rate for all-cause dementia
  • Hazard ratio (HR) 1.24 (95% CI, 1.17 to 1.33)
• Increasing durations of use yielded higher hazard ratios
  • ≤1 year of use: HR 1.21 (95% CI, 1.09 to 1.35)
  • >12 years of use: HR 1.74 (95% CI, 1.45 to 2.10)
• Estrogen-progestogen therapy was positively associated with development of dementia for both
  • Continuous regimens: HR 1.31 (95% CI, 1.18 to 1.46)
  • Cyclic regimens: HR 1.24 (95% CI, 1.13 to 1.35)
• Associations persisted in women who received treatment at ≤55 years
  • HR 1.24 (95% CI, 1.11 to 1.40)
• Findings persisted when restricted to
  • Late onset dementia (≥65 years): HR 1.21 (95% CI, 1.12 to 1.30)
  • Alzheimer’s disease: HR 1.22 (95% CI, 1.07 to 1.39)

CONCLUSION:

• Menopausal hormone therapy was associated with an increased risk of all-cause dementia, late onset dementia and Alzheimer’s disease
  • Risk persisted even in women who received hormone therapy at 55 years of age or younger
• Authors acknowledge that study is associative and not causative
  • Can not determine if actual effect of hormone therapy on dementia risk or underlying predisposition among women who need hormone therapy

Accompanying Editorial

• An accompanying editorial recognizes study strengths, including use of the entire population of Denmark
• The editorial provides multiple examples of confounding, including the possibility that women who have subjective cognitive changes and sleep disturbance during transition may be more likely to seek out hormone therapy
• RCTs that focused on younger women (50 to 55 years) did not show a negative impact
• The authors of the editorial conclude that

… the observed associations could be artefactual and should not be used to infer a causal relationship between hormone therapy and dementia risk

These findings cannot inform shared decision making about use of hormone therapy for menopausal symptoms 

Learn More – Primary Sources:

Menopausal hormone therapy and dementia: nationwide, nested case-control study