Postmenopausal hormone therapy and regional brain volumes

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 amongwomen aged 65 years and older; however, the adverse effects are most evident in women experiencing cognitive deficits before initiating hormone therapy. Neurology 2009;72: 135–142