Kejal Kantarci, Firat Kara, Nirubol Tosakulwong, Angela J. Fought, Christopher G Schwarz, Matthew L. Senjem, June Kendall-Thomas, Paul H. Min, VJ Lowe, Clifford R Jack, Ekta Kapoor, Julie A. Fields, Kent R. Bailey, Taryn T. James, Laura L. Faubion, Lobo Ra, JoAnn E Manson, Lubna Pal, Dustin B Hammers, Eliot A. Brinton, Michael Malek-Ahmadi, Marcelle I. Cedars, Frederick N Naftolin, N. Santoro, V. M. Miller, Sherman Harman, N. Maritza Dowling, Carey E Gleason
INTRODUCTION: Associations of short-term use of menopausal hormone therapy (mHT) with Alzheimer's disease (AD) and structural magnetic resonance imaging (MRI) biomarkers were investigated 10 years after an mHT trial. METHODS: Recently menopausal women with good cardiovascular health were randomized to oral conjugated equine estrogens (oCEE) or transdermal 17β-estradiol (tE2) and micronized progesterone, or placebo for 4 years. Amyloid beta (Aβ) on positron emission tomography, hippocampal atrophy, and dorsolateral prefrontal cortex thickness on MRI were assessed 10 years after completion of the mHT trial (n = 266). RESULTS: Aβ and structural MRI biomarkers were not different in the oCEE and tE2 groups compared to placebo. Apolipoprotein E ε4 status did not modify the findings. DISCUSSION: There was no evidence of adverse effects or benefits associated with 4 years of use of oral or transdermal mHT on Aβ and structural MRI biomarkers in relatively healthy women, 10 years after mHT. Findings support the long-term safety of short-term use of mHT on brain health. CLINICAL TRIALS REGISTRATION: NCT00154180 Kronos Early Estrogen Prevention Study (KEEPS) HIGHLIGHTS: There were no menopausal hormone therapy-related adverse effects or benefits on amyloid beta and magnetic resonance imaging biomarkers in the long term. Apolipoprotein E ε4 carrier status did not modify these findings. Findings align with neutral cognitive and cerebrovascular outcomes in this cohort.