Early Postmenopausal Transdermal 17β-Estradiol Therapy and Amyloid-β Deposition

J Alzheimers Dis. 2016 May 7;53(2):547-56. doi: 10.3233/JAD-160258.


Background: It remains controversial whether hormone therapy in recently postmenopausal women modifies the risk of Alzheimer's disease (AD).

Objective: To investigate the effects of hormone therapy on amyloid-β deposition in recently postmenopausal women.

Methods: Participants within 5-36 months past menopause in the Kronos Early Estrogen Prevention Study, a randomized, double blinded placebo-controlled clinical trial, were randomized to: 1) 0.45 mg/day oral conjugated equine estrogens (CEE); 2) 50μg/day transdermal 17β-estradiol; or 3) placebo pills and patch for four years. Oral progesterone (200 mg/day) was given to active treatment groups for 12 days each month. 11C Pittsburgh compound B (PiB) PET imaging was performed in 68 of the 118 participants at Mayo Clinic approximately seven years post randomization and three years after stopping randomized treatment. PiB Standard unit value ratio (SUVR) was calculated.

Results: Women (age = 52-65) randomized to transdermal 17β-estradiol (n = 21) had lower PiB SUVR compared to placebo (n = 30) after adjusting for age [odds ratio (95% CI) = 0.31(0.11-0.83)]. In the APOEɛ4 carriers, transdermal 17β-estradiol treated women (n = 10) had lower PiB SUVR compared to either placebo (n = 5) [odds ratio (95% CI) = 0.04(0.004-0.44)], or the oral CEE treated group (n = 3) [odds ratio (95% CI) = 0.01(0.0006-0.23)] after adjusting for age. Hormone therapy was not associated with PiB SUVR in the APOEɛ4 non-carriers.

Conclusion: In this pilot study, transdermal 17β-estradiol therapy in recently postmenopausal women was associated with a reduced amyloid-β deposition, particularly in APOEɛ4 carriers. This finding may have important implications for the prevention of AD in postmenopausal women, and needs to be confirmed in a larger sample.

Keywords: Alzheimer’s disease; PET; amyloid-β; cognitive function; estrogen; hormone therapy; menopause; prevention.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Cutaneous
  • Administration, Oral
  • Adult
  • Aged
  • Alzheimer Disease / drug therapy*
  • Aniline Compounds / pharmacokinetics
  • Apolipoproteins E / genetics
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Cognition / drug effects*
  • Double-Blind Method
  • Estradiol / administration & dosage*
  • Estradiol / pharmacology*
  • Estrogens / administration & dosage
  • Estrogens / pharmacology
  • Estrogens, Conjugated (USP) / administration & dosage
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Neuropsychological Tests
  • Postmenopause / drug effects*
  • Postmenopause / metabolism*
  • Retrospective Studies
  • Thiazoles / pharmacokinetics


  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Aniline Compounds
  • Apolipoproteins E
  • Estrogens
  • Estrogens, Conjugated (USP)
  • Thiazoles
  • Estradiol