Clinical Question: Does postmenopausal estrogen therapy improve global cognitive function?

Setting: Outpatient (any)

Study Design: Randomized controlled trial (double-blinded)

Allocation to Groups: Concealed

Synopsis: The Women’s Health Initiative Memory Study previously reported that combined hormone therapy with estrogen and progesterone does not improve global cognitive function in postmenopausal women. To determine the effect of hormone therapy with estrogen alone, 2,947 women 65 to 79 years of age with previous hysterectomy were randomized in double-blind fashion to receive 0.625 mg per day of conjugated equine estrogen or matching placebo. Persons assessing outcomes were blinded to treatment group assignment. Follow-up was complete for more than 95 percent of the study participants for a mean of 5.4 years. Using intention-to-treat analysis, mean Mini-Mental State Examination scores were 0.26 units lower in the estrogen-treated group than in the placebo group (P = .04). The adverse effects of estrogen were more pronounced in women with a lower score on cognitive function at baseline.

Bottom Line: Postmenopausal estrogen therapy does not improve—and may worsen—global cognitive function. Adverse effects may be more pronounced in women with preexisting reduced cognitive function. (Level of Evidence: 1b)