Postmenopausal hormone therapy and regional brain volumes: The WHIMS-MRI Study

S. M. Resnick, M. A. Espeland, S. A. Jaramillo, Calvin H Hirsch, M. L. Stefanick, A. M. Murray, J. Ockene, C. Davatzikos

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Abstract

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 lower among women assigned to HT (p = 0.004), mean hippocampal volume was slightly (0.10 cm) 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 (scores <90). CONCLUSIONS:: 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.

Original languageEnglish (US)
Pages (from-to)135-142
Number of pages8
JournalNeurology
Volume72
Issue number2
DOIs
StatePublished - Jan 13 2009

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ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Resnick, S. M., Espeland, M. A., Jaramillo, S. A., Hirsch, C. H., Stefanick, M. L., Murray, A. M., Ockene, J., & Davatzikos, C. (2009). Postmenopausal hormone therapy and regional brain volumes: The WHIMS-MRI Study. Neurology, 72(2), 135-142. https://doi.org/10.1212/01.wnl.0000339037.76336.cf