Postmenopausal hormone therapy and regional brain volumes: the WHIMS-MRI Study
Department of Medicine, Division of Preventive and Behavioral Medicine
Age Factors; Aged; Atrophy; Brain; Causality; Cognition Disorders; Dementia; Estrogen Replacement Therapy; Estrogens; Estrogens, Conjugated (USP); Female; Hippocampus; Humans; Magnetic Resonance Imaging; Neuropsychological Tests; Prefrontal Cortex
Life Sciences | Medicine and Health Sciences | Women's Studies
OBJECTIVES: To determine whether menopausal hormone therapy (HT) affects regional brain volumes, including hippocampal and frontal regions.
METHODS: Brain MRI scans were obtained in a subset of 1,403 women aged 71-89 years who participated in the Women's Health Initiative Memory Study (WHIMS). WHIMS was an ancillary study to the Women's Health Initiative, which consisted of two randomized, placebo-controlled trials: 0.625 mg conjugated equine estrogens (CEE) with or without 2.5 mg medroxyprogesterone acetate (MPA) in one daily tablet. Scans were performed, on average, 3.0 years post-trial for the CEE + MPA trial and 1.4 years post-trial for the CEE-Alone trial; average on-trial follow-up intervals were 4.0 years for CEE + MPA and 5.6 years for CEE-Alone. Total brain, ventricular, hippocampal, and frontal lobe volumes, adjusted for age, clinic site, estimated intracranial volume, and dementia risk factors, were the main outcome variables.
RESULTS: Compared with placebo, covariate-adjusted mean frontal lobe volume was 2.37 cm(3) lower among women assigned to HT (p = 0.004), mean hippocampal volume was slightly (0.10 cm(3)) lower (p = 0.05), and differences in total brain volume approached significance (p = 0.07). Results were similar for CEE + MPA and CEE-Alone. HT-associated reductions in hippocampal volumes were greatest in women with the lowest baseline Modified Mini-Mental State Examination scores (scoresCONCLUSIONS: Conjugated equine estrogens with or without MPA are associated with greater brain atrophy among women aged 65 years and older; however, the adverse effects are most evident in women experiencing cognitive deficits before initiating hormone therapy.
DOI of Published Version
Neurology. 2009 Jan 13;72(2):135-42. Link to article on publisher's site
Resnick, Susan M.; Espeland, Mark A.; Jaramillo, Sarah A.; Hirsch, C.; Stefanick, Marcia L.; Murray, A. M.; Ockene, Judith K.; and Davatzikos, C., "Postmenopausal hormone therapy and regional brain volumes: the WHIMS-MRI Study" (2009). Women’s Health Research Faculty Publications. 494.