Randomization to hormone therapy and changes in plasma biomarkers of Alzheimer's pathology: The women's health initiative memory study

Maturitas. 2026 Apr:207:108873. doi: 10.1016/j.maturitas.2026.108873. Epub 2026 Feb 11.

Abstract

The association of hormone therapy with Alzheimer's pathology among postmenopausal women is not well understood. We examined the association of randomized assignment to hormone therapy with changes in plasma biomarkers of Alzheimer's pathology in the Women's Health Initiative Memory Study. Rates of change in the biomarkers (p-tau217, p-tau181, Aβ42:Aβ40, GFAP, and NfL) over an average 15-year follow-up did not significantly differ for estrogen alone vs placebo or estrogen plus progestin vs placebo. These null associations do not support either a protective or a detrimental association of hormone therapy of the types tested in the Women's Health Initiative with long-term changes in plasma Alzheimer's biomarkers. CLINICALTRIALS.GOV: NCT00685009.

Keywords: Alzheimer's disease; Dementia; GFAP; Hormone therapy; Menopause; NfL; P-tau217; Plasma biomarkers; Women's health.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Alzheimer Disease* / blood
  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides / blood
  • Biomarkers / blood
  • Estrogen Replacement Therapy*
  • Estrogens* / therapeutic use
  • Female
  • Glial Fibrillary Acidic Protein / blood
  • Humans
  • Middle Aged
  • Neurofilament Proteins / blood
  • Peptide Fragments / blood
  • Postmenopause*
  • Progestins* / therapeutic use
  • Women's Health
  • tau Proteins / blood

Substances

  • Biomarkers
  • tau Proteins
  • Amyloid beta-Peptides
  • Glial Fibrillary Acidic Protein
  • Neurofilament Proteins
  • Estrogens
  • Progestins
  • neurofilament protein L
  • Peptide Fragments
  • GFAP protein, human
  • amyloid beta-protein (1-42)

Associated data

  • ClinicalTrials.gov/NCT00685009