The effect of 3-year treatment with 0.25 mg/day of micronized 17beta-estradiol on cognitive function in older postmenopausal women.

Objectives: To evaluate the effect of ultra-low-dose (0.25 mg/d) micronized 17beta-estradiol on cognitive function in older postmenopausal women.

Design: Randomized, placebo-controlled trial conducted for 3 years.

Setting: Academic health center in greater Hartford, Connecticut.

Participants: Fifty-seven healthy, community-dwelling, older postmenopausal women.

Intervention: Women received 0.25 mg/d of micronized 17beta-estradiol (estrogen therapy (ET), n=32) or placebo (n=25); all women who had not had a hysterectomy received 100 mg/d of oral micronized progesterone for 2-week periods every 6 months.

Measurements: Neuropsychological measures of memory, language, mood, and executive function were collected at baseline, 3 months, and 36 months. Measures of executive function included the Controlled Oral Word Association Test, the Trail Making Test, and the Wisconsin Card Sorting Test. The Boston Naming Test was used to measure language skills. The Symbol Digit Modalities Test was used as a measure of sustained attention. Measures of memory included the Complex Figure Test, Fuld Object Memory Test, and a selected subtest from the Wechsler Memory Scale. Scores from the Geriatric Depression Scale and the Beck Anxiety Inventory were used to assess symptoms of depression.

Results: No differences were found between ET and placebo on any of the neurocognitive measures or depression instruments, nor were there any differences when the groups were stratified according to age.

Conclusion: This small study, which had adequate power to detect change in some but not all domains of cognition tested, revealed that low-dose estrogen neither benefits nor harms cognitive function in older women after 3 years of treatment, but confirmation is needed from larger trials.