Conjugated Equine Estrogens and Incidence of Probable Dementia and Mild Cognitive Impairment in Postmenopausal Women: Women???s Health Initiative Memory Study

Abstract

Previous findings from the Women’s Health Initiative Memory Study (WHIMS) have suggested an increased risk of dementia, but not mild cognitive impairment (MCI), in women given conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA). The present report presents data from the WHIMS, a randomized, double-blind, placebo-controlled trial, when assessing the effects of CEE alone and CEE plus MPA on the risk of dementia and MIC in community-living women 65 to 79 years of age. The participants, including 4532 women given estrogen plus progestin and 2947 given estrogen only, entered the trial in the years 1995–2002. Women received a daily tablet of 0.625 mg CEE or matching placebo, or else a combination of 0.625 mg CEE and 2.5 mg MPA daily with matching placebos. The women were screened annually using the Modified Mini-Mental State Examination and, if indicated, underwent a battery of neuropsychologic tests and standardized interviews. The risk of probable dementia during follow up was 49% greater in women assigned to CEE compared with placebo recipients (37 vs. 25 per 10,000 person-years). Comparable rates of probable dementia were recorded for women in the CEE alone and CEE plus MPA group, and the hazard ratios (HRs) did not differ significantly. The risk of MCI was 34% higher in women taking CEE alone than in their matched placebo recipients (HR, 1.34). There was no significant increase in risk in the combined medication trial. The hazard ratio for either probable dementia or MCI in women given CEE alone, compared with placebo women, was 1.38. These findings from the WHIMS indicate that older women who take CEE alone or CEE plus MPA are at increased risk of dementia or MCI. The investigators recommend that women aged 65 and older not be given hormone therapy with the goal of preventing dementia or MCI.