Cognitive Effects of Hormone Therapy Continuation or Discontinuation in a Sample of Women at Risk for Alzheimer Disease

Am J Geriatr Psychiatry. 2015 Nov;23(11):1117-26. doi: 10.1016/j.jagp.2015.05.009. Epub 2015 May 21.


Objective: Use of estrogen-based hormone therapy (HT) as a protection from cognitive decline and Alzheimer disease (AD) is controversial, although cumulative data support HT use when initiated close to menopause onset with estrogen formulations containing 17β-estradiol preferable to conjugated equine estrogen formulations. Little is known regarding specific populations of women who may derive benefit from HT.

Methods: Women with heightened risk for AD (aged 49-69), all of whom were taking HT for at least 1 year and most of whom initiated HT close to menopause onset, underwent cognitive assessment followed by randomization to continue or discontinue HT. Assessments were repeated at 2 years after randomization.

Results: Women who continued HT performed better on cognitive domains composed of measures of verbal memory and combined attention, working memory, and processing speed measures. Women who used 17β-estradiol versus conjugated equine estrogen, whether randomized to continue or discontinue HT, showed better verbal memory performance at the 2-year follow-up assessment. An interaction was also found with HT randomization and family history of AD in a first-degree relative. All female offspring of patients with AD declined in verbal memory; however, women who continued HT declined less than women who discontinued HT. Women without a first-degree relative with AD showed verbal memory improvement (likely because of practice effects) with continuance and declined with discontinuance of HT.

Conclusion: Continuation of HT use appears to protect cognition in women with heightened risk for AD when initiated close to menopause onset.

Keywords: Alzheimer disease; Hormone therapy; cognition; postmenopausal women.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Alzheimer Disease / prevention & control*
  • Cognition / drug effects*
  • Estradiol / therapeutic use*
  • Estrogen Replacement Therapy* / psychology
  • Female
  • Humans
  • Menopause / drug effects
  • Middle Aged
  • Risk Factors


  • Estradiol