Long-Term Effects of Conjugated Equine Estrogen Therapies on Domain-Specific Cognitive Function: Results from the Women's Health Initiative Study of Cognitive Aging Extension

Authors

  • Mark A. Espeland PhD,

    1. From the *Division of Public Health Sciences and Department of Psychiatry, Wake Forest University Health Sciences, Winston-Salem, North Carolina; Department of Family and Community Medicine, School of Medicine, University of Nevada, Reno, Nevada; §Department of Preventive Medicine, State University of New York, Stony Brook, New York; and Laboratory of Personality and Cognition/03, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
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  • Robert L. Brunner PhD,

    1. From the *Division of Public Health Sciences and Department of Psychiatry, Wake Forest University Health Sciences, Winston-Salem, North Carolina; Department of Family and Community Medicine, School of Medicine, University of Nevada, Reno, Nevada; §Department of Preventive Medicine, State University of New York, Stony Brook, New York; and Laboratory of Personality and Cognition/03, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
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  • Patricia E. Hogan MS,

    1. From the *Division of Public Health Sciences and Department of Psychiatry, Wake Forest University Health Sciences, Winston-Salem, North Carolina; Department of Family and Community Medicine, School of Medicine, University of Nevada, Reno, Nevada; §Department of Preventive Medicine, State University of New York, Stony Brook, New York; and Laboratory of Personality and Cognition/03, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
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  • Stephen R. Rapp PhD,

    1. From the *Division of Public Health Sciences and Department of Psychiatry, Wake Forest University Health Sciences, Winston-Salem, North Carolina; Department of Family and Community Medicine, School of Medicine, University of Nevada, Reno, Nevada; §Department of Preventive Medicine, State University of New York, Stony Brook, New York; and Laboratory of Personality and Cognition/03, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
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  • Laura H. Coker PhD,

    1. From the *Division of Public Health Sciences and Department of Psychiatry, Wake Forest University Health Sciences, Winston-Salem, North Carolina; Department of Family and Community Medicine, School of Medicine, University of Nevada, Reno, Nevada; §Department of Preventive Medicine, State University of New York, Stony Brook, New York; and Laboratory of Personality and Cognition/03, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
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  • Claudine Legault PhD,

    1. From the *Division of Public Health Sciences and Department of Psychiatry, Wake Forest University Health Sciences, Winston-Salem, North Carolina; Department of Family and Community Medicine, School of Medicine, University of Nevada, Reno, Nevada; §Department of Preventive Medicine, State University of New York, Stony Brook, New York; and Laboratory of Personality and Cognition/03, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
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  • Iris Granek PhD,

    1. From the *Division of Public Health Sciences and Department of Psychiatry, Wake Forest University Health Sciences, Winston-Salem, North Carolina; Department of Family and Community Medicine, School of Medicine, University of Nevada, Reno, Nevada; §Department of Preventive Medicine, State University of New York, Stony Brook, New York; and Laboratory of Personality and Cognition/03, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
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  • Susan M. Resnick PhD,

    1. From the *Division of Public Health Sciences and Department of Psychiatry, Wake Forest University Health Sciences, Winston-Salem, North Carolina; Department of Family and Community Medicine, School of Medicine, University of Nevada, Reno, Nevada; §Department of Preventive Medicine, State University of New York, Stony Brook, New York; and Laboratory of Personality and Cognition/03, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
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  • for the Women's Health Initiative Study of Cognitive Aging Study Group

    1. From the *Division of Public Health Sciences and Department of Psychiatry, Wake Forest University Health Sciences, Winston-Salem, North Carolina; Department of Family and Community Medicine, School of Medicine, University of Nevada, Reno, Nevada; §Department of Preventive Medicine, State University of New York, Stony Brook, New York; and Laboratory of Personality and Cognition/03, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
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Address correspondence to Mark A. Espeland, Department of Biostatistical Sciences, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157. E-mail: mespelan@wfubmc.edu

Abstract

OBJECTIVES: To determine whether small decrements in global cognitive function that conjugated equine estrogen (CEE) therapies have been shown to produce in older women persist after cessation and extend to specific cognitive domains.

DESIGN: Randomized controlled clinical trial.

SETTING: Fourteen clinical centers of the Women's Health Initiative.

PARTICIPANTS: Two thousand three hundred four women aged 65 to 80 free of probable dementia at enrollment.

INTERVENTION: CEE 0.625 mg/d with or without medroxyprogesterone acetate (MPA, 10 mg/d) and matching placebos.

MEASUREMENTS: Annual administrations of a battery of cognitive tests during and after the trial.

RESULTS: Assignment to CEE-based therapies was associated with small mean relative decrements in global cognitive function and several domain-specific cognitive functions during the trial, which largely persisted through up to 4 years after the trial. The strongest statistical evidence was for global cognitive function (0.07–standard deviation decrements during (P=.007) and after (P=.01) the trial. For domain-specific scores, the mean decrements were slightly smaller, were less significant, and tended to be larger for CEE-alone therapy.

CONCLUSION: CEE-based therapies, when initiated after the age of 65, produce a small broad-based decrement in cognitive function that persists after their use is stopped, but the differences in cognitive function are small and would not be detectable or have clinical significance for an individual woman. Differences in effects between cognitive domains suggest that more than one mechanism may be involved.

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