Postmenopausal HT tied to increased risk for Alzheimer’s disease

  • Savolainen-Peltonen H & al.
  • BMJ
  • 6 Mar 2019

  • International Clinical Digest
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  • Postmenopausal women using systemic hormone therapy had a 9%-17% higher risk for Alzheimer’s disease.

Why this matters

  • Data on this association have been mixed.

Key results

  • Risk for Alzheimer’s disease with systemic hormone therapy similarly elevated for:
    • Users of estradiol only (OR, 1.09; 95% CI, 1.05-1.14).
    • Users of estrogen-progestogen (OR, 1.17; 95% CI, 1.13-1.21).
  • Among users of estrogen-progestogen, elevation of risk did not differ significantly according to the progestogen (norethisterone acetate, medroxyprogesterone acetate, other).
  • Women starting hormone therapy before age 60 years had increased risk with long-term exposure (≥10 years; OR, 1.07; 95% CI, 1.00-1.15).
  • Risk was not influenced by age at initiation.
  • Women using only vaginal estradiol did not have elevated risk (OR, 0.99; 95% CI, 0.96-1.01).

Expert comment

  • In an editorial, Pauline M. Maki, MD, and colleagues write, “Considering the totality of the evidence, these findings should not influence clinical decision making about the use of hormone therapy for symptom management. For women in early menopause with bothersome vasomotor symptoms, no compelling evidence exists of cognitive concern from randomized trials and instead there is reassurance about cognitive safety. Concerns about longer term use of estrogen plus progestin on cognitive outcomes remain.”

Study design

  • Finnish nationwide case-control study using population and drug registry data for 1999-2013:
    • 84,739 cases: postmenopausal women receiving a diagnosis of Alzheimer’s disease from neurologist or geriatrician.
    • 84,739 controls: age- and district-matched postmenopausal women not receiving that diagnosis.
  • Main outcome: Alzheimer’s disease.
  • Funding: Helsinki University Hospital; Jane and Aatos Erkko Foundation.


  • Ascertainment bias.
  • Confounding by indication.
  • Significant associations possibly related to large sample size.