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The Women’s Health Initiative Memory Study (WHIMS) was an ancillary study to the Women’s Health Initiative (WHI) that investigated the impact of hormone therapy on risk for dementia in women 65 years of age and older [1,2]. Among naturally menopausal women (n = 4532), the hazard ratio for probable dementia among women receiving conjugated equine estrogen (CEE) (0.625 mg/day) plus medroxyprogesterone acetate (MPA) (2.5 mg/day) compared with those assigned to placebo was 2.05 (95% confidence interval (CI), 1.21–3.48; p = 0.01). Among surgically menopausal women (n = 2947) randomized to CEE alone versus placebo, the hazard ratio was 1.49 (95% CI, 0.83–2.66, non-significant). Hormone therapy (HT) also increased the risk of decline on the Mini-Mental State Exam in the WHI [3,4]. 


Two new reports from the WHIMS Magnetic Resonance Imaging (MRI) Study shed new light on mechanisms that might contribute to this cognitive decline. Both studies used data from a subset of 1403 women participating in the two arms of WHIMS. Neither study included pretreatment baseline measures. For the CEE/MPA group, MRI outcomes were collected on average 3 years post-trial and after an average of 4 years of on-trial treatment. For the CEE-alone group, outcome variables were collected on average 1.5 years post-trial and after an average of 5.6 years. The mean age of women at the time of the MRI assessments was 78 years. Thus, these results address the impact of long-duration hormone therapy in elderly women.


The first study examined subclinical cerebrovascular disease [5]. Counter to predictions, mean ischemic brain lesion volumes did not differ significantly between women randomized to hormone therapy versus placebo.  


The second study investigated the impact of hormone therapy on regional brain volumes [6]. Total brain volume, ventricle volume, hippocampal volume and frontal lobe volume were measured. In pooled analyses, but not in each arm individually, frontal lobe volume was significantly reduced among women randomized to receive hormone therapy. Subanalyses examined whether the magnitude of decline in brain volume varied with pretreatment cognitive status and with the magnitude of ischemic lesion volume. Hippocampal volume varied with baseline cognitive status, with the greatest volume loss evident in women with the poorest cognitive status. Total brain volume, hippocampal volume and frontal lobe volume were each reduced more among women with relatively high ischemic brain lesion volumes compared with women with relatively low ischemic brain volumes.


  • Pauline Maki
    Associate Professor of Psychiatry and Psychology, Center for Cognitive Medicine, University of Illinois at Chicago, Chicago, USA


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