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Arch Neurol. 2006 Jul;63(7):945-50.

Effects of ultra-low-dose transdermal estradiol on cognition and health-related quality of life.

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  • 1Department of Psychiatry, University of California, San Francisco, CA 94121, USA.



Several small trials and many observational studies suggest that estrogen treatment in postmenopausal women improves cognition, but 2 large randomized trials have shown harm. The effect of an ultra-low- dose of unopposed transdermal estradiol on cognition and health-related quality of life is unknown.


To investigate the effect of unopposed ultra-low-dose transdermal estradiol on cognitive function and quality of life in postmenopausal women.


Randomized, placebo-controlled, double-blind trial with 2-year follow-up. The main outcome of the trial was change in bone density. Changes in cognitive function and quality of life were preplanned secondary outcomes of the trial.


Nine clinical centers in the United States.


Postmenopausal women (N = 417), aged 60 to 80 years, with a normal bone density for age and an intact uterus.


A weekly transdermal patch that delivers estradiol, 0.014 mg/d (n = 208), or placebo (n = 209).


Seven standardized cognitive tests (a total of 10 scores) administered at baseline and years 1 and 2 to test global cognitive function, verbal and visuospatial memory, language, executive function, and semantic memory. The 36-Item Short-Form General Health Survey was administered to assess health-related quality of life in physical and mental domains. The sample size provided 80% power to detect a standardized effect of 0.29 SD, a small-to-moderate difference.


Baseline characteristics were similar in the 2 treatment groups. At 2 years of follow-up, we found no statistically significant differences between treatment groups in change on any of the cognitive test scores or on the 36-Item Short-Form General Health Survey (P > .12 for all). There was no consistent evidence that the effect of treatment on change in cognitive or 36-Item Short-Form General Health Survey scores depended on the level of baseline endogenous estradiol.


Postmenopausal treatment with ultra-low-dose unopposed transdermal estradiol for 2 years had no effect on change in cognitive function or in health-related quality of life over 2 years of treatment.

[PubMed - indexed for MEDLINE]
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