Clinical Question: Does estrogen therapy alone reduce the risk of dementia and cognitive impairment in postmenopausal women?

Setting: Outpatient (specialty)

Study Design: Randomized controlled trial (double-blinded)

Allocation to Groups: Concealed

Synopsis: The Women’s Health Initiative Memory Study previously reported an increased risk of dementia, but no effect on mild cognitive impairment, in women treated with both estrogen and progesterone. In this estrogen-alone trial arm of the same study, 2,947 postmenopausal women 65 to 79 years of age were randomized in a double-blind fashion to receive 0.625 mg per day of conjugated equine estrogen or matching placebo. Outcomes were assessed by persons blinded to treatment group assignment. Follow-up was complete for more than 95 percent of the study participants for an average of 5.4 years. Using intention-to-treat analysis, women receiving estrogen-alone therapy were at a nonsignificantly increased risk of being diagnosed with dementia and mild cognitive impairment.

Bottom Line: Estrogen therapy alone does not reduce—and may actually increase—the risk of dementia and mild cognitive impairment in postmenopausal women 65 years or older. (Level of Evidence: 1b)