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Data from the Women’s Health Initiative Memory Study (WHIMS) were analyzed to determine whether conjugated equine estrogen (CEE) influences global cognitive function in women 65 to 79 years of age, and to compare its effects with those of CEE plus medroxyprogesterone acetate (MPA). Using a randomized, double-blind, placebo-controlled design, cognitive function was assessed in community-living women who had undergone hysterectomy. Baseline and follow-up information was available for 2808 women at 39 centers without probable dementia at the outset. They received either 1 daily tablet containing 0.625 mg of CEE or a matching placebo. Global cognitive function was estimated annually using the Modified Mini-Mental State Examination (3MSE). In both CEE and placebo recipients, 3SME scores tended to rise over time during the first 4 years. Placebo recipients had slightly higher mean scores. Subsequently, this increase became less evident. Test scores were lower in women assigned to receive CEE than in placebo patients during a mean follow up of 5.4 years. When the data were combined with those from the combined estrogen–progestin part of the WHIMS, women assigned to hormone therapy had lower mean 3MSE scores. Differences were less marked when women having dementia, mild cognitive impairment, or stroke were excluded from analysis. Adverse effects of hormone therapy were most evident in women having relatively less cognitive function at baseline. Serial 3MSE scores in women aged 65 and over in this trial indicated that those who received CEE had slightly but significantly lower average cognitive function than did placebo recipients. The effects of CEE alone were similar to those of CEE plus MPA in the combined treatment part of the study. The investigators conclude that neither CEE nor combined CEE-MPA should be given to older women with the object of preventing cognitive dysfunction. Women with relatively low cognitive function at baseline were especially vulnerable to the adverse effects of hormone therapy.
Espeland et al. (Wed,) studied this question.