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
Mark A Espeland, Robert L Brunner, Patricia E Hogan, Stephen R Rapp, Laura H Coker, Claudine Legault, Iris Granek, Susan M Resnick, Women's Health Initiative Study of Cognitive Aging Study Group, Sally Shumaker, Stephen Rapp, Mark Espeland, Laura Coker, Deborah Farmer, Anita Hege, Patricia Hogan, Darrin Harris, Cynthia McQuellon, Anne Safrit, Lee Ann Andrews, Candace Warren, Carolyn Bell, Linda Allred, Carol Murphy, Linda Powell, Rebecca Jackson, John Robbins, Robert Wallace, Marian Limacher, Howard Judd, Jane Kotchen, Karen Margolis, Robert Brunner, Sylvia Smoller, Marcia Stefanick, Dorothy Lane, Judith Ockene, Mary Haan, Richard Grimm, Sandra Daugherty, Barbara Alving, Jacques Rossouw, Linda Pottern, Deborah Bowen, Gretchen Van Lom, Carolyn Burns, Mark A Espeland, Robert L Brunner, Patricia E Hogan, Stephen R Rapp, Laura H Coker, Claudine Legault, Iris Granek, Susan M Resnick, Women's Health Initiative Study of Cognitive Aging Study Group, Sally Shumaker, Stephen Rapp, Mark Espeland, Laura Coker, Deborah Farmer, Anita Hege, Patricia Hogan, Darrin Harris, Cynthia McQuellon, Anne Safrit, Lee Ann Andrews, Candace Warren, Carolyn Bell, Linda Allred, Carol Murphy, Linda Powell, Rebecca Jackson, John Robbins, Robert Wallace, Marian Limacher, Howard Judd, Jane Kotchen, Karen Margolis, Robert Brunner, Sylvia Smoller, Marcia Stefanick, Dorothy Lane, Judith Ockene, Mary Haan, Richard Grimm, Sandra Daugherty, Barbara Alving, Jacques Rossouw, Linda Pottern, Deborah Bowen, Gretchen Van Lom, Carolyn Burns
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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Source: PubMed