Abstract 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.
Associations of blood pressure with white matter hyperintensities later in life; influence of short-term menopausal hormone therapy
Abstract Objective To assess the association of systolic and diastolic blood pressure (SBP and DBP) in recently menopausal women with white matter hyperintensity (WMH) volume later in life and determine whether short-term menopausal hormone therapy (mHT) modifies these associations. Methods Kronos Early Estrogen Prevention Study (KEEPS) was a multicenter, randomized, double-blinded, placebo-controlled 4-year mHT trial (oral conjugated equine estrogens or transdermal 17β-estradiol). KEEPS continuation was an observational follow-up of the participants 10 years after the end of mHT. The associations between KEEPS baseline blood pressure (BP) with KEEPS continuation WMH volume were examined adjusting for covariates in model 1 (age, total intracranial volume, study site, mHT type) and model 2 (additionally conventional CVD risk factors). Interaction terms (BP × mHT type) were added into the linear regression models. Results The mean ± SD ages of participants were 53 (±2) years at KEEPS baseline and 67 (±2) years at KEEPS continuation. Elevated BP at KEEPS baseline was associated with greater WMH volume measured 14 years later (model 1: SBP: β = 0.01 [95% CI, 0.001‐0.01] and DBP: β = 0.01 [95% CI, 0.003‐0.03]) and after additionally adjusting for CVD risk factors (model 2). We did not find any evidence that mHT versus placebo modified these associations. Topographically, higher BP was associated with greater periventricular WMH in the frontal and parietal lobes. Conclusion Our findings suggest the importance of maintaining normal BP in recently postmenopausal women with low CVD risk, irrespective of short-term mHT usage, to potentially reduce the risk of WMH later in life.