Stroke Findings in the Women's Health Initiative

Abstract

The Women's Health Initiative (WHI) clinical trials of estrogen with or without progestin versus placebo in 27,341 postmenopausal women are the largest randomized, placebo-controlled, double-blind clinical trials to look at the effect of hormone therapy on the outcomes of stroke, dementia, and cognition. Data from a parallel prospective observational study of 93,676 women examine biomarkers and risk factors associated with stroke. We summarize the results of 29 published articles in the WHI with stroke or cognition as outcomes of interest. Estrogen alone or in combination with progestin resulted in approximately 50% excess risk of ischemic stroke and in a 76% excess risk of dementia in women 65 years or older. Other risk factors for stroke identified in the WHI were panic attacks, depression, use of antidepressants (particularly selective serotonin reuptake inhibitors for hemorrhagic but not ischemic stroke), high triglycerides, low walking speed, long sleep duration, certain inflammatory factors, and systolic blood pressure variability. Hormone therapy has adverse effects on the brain as manifested by higher risks of stroke and dementia. Additional risk factors for stroke identified in WHI should be followed up to determine if reversing them would result in lower stroke rates.

Keywords

stroke - hormone therapy - Women's Health Initiative - WHI - dementia - postmenopausal women

WHI Investigators

Program Office: Jacques Rossouw, Shari Ludlam, Dale Burwen, Joan McGowan, Leslie Ford, and Nancy Geller (National Heart, Lung, and Blood Institute, Bethesda, MD).

Clinical Coordinating Center: Garnet Anderson, Ross Prentice, Andrea LaCroix, Charles Kooperberg, Barbara Cochrane, Julie Hunt, Marian Neuhouser, Lesley Tinker, Susan Heckbert, and Alex Reiner (Fred Hutchinson Cancer Research Center, Seattle, WA).

Regional Centers: JoAnn E. Manson, Kathryn M. Rexrode, Brian Walsh, J. Michael Gaziano, and Maria Bueche (Brigham and Women's Hospital, Harvard Medical School, Boston, MA); Barbara V. Howard, Lucile Adams-Campbell, Lawrence Lessin, Cheryl Iglesia, Brian Walitt, and Amy Park (MedStar Health Research Institute/Howard University, Washington, DC); Rebecca Jackson, Randall Harris, Electra Paskett, W. Jerry Mysiw, and Michael Blumenfeld (The Ohio State University, Columbus, OH); Marcia L. Stefanick, Mark A. Hlatky, Manisha Desai, Jean Tang, and Stacy T. Sims (Stanford Prevention Research Center, Stanford, CA); Cynthia A. Thomson, Tamsen Bassford, Cheryl Ritenbaugh, Zhao Chen, and Marcia Ko (University of Arizona, Tucson/Phoenix, AZ); Jean Wactawski-Wende, Maurizio Trevisan, Ellen Smit, Amy Millen, Michael LaMonte (University at Buffalo, Buffalo, NY); Marian Limacher, Michael Perri, Andrew Kaunitz, R. Stan Williams, and Yvonne Brinson(University of Florida, Gainesville/Jacksonville, FL); Robert Wallace, James Torner, Susan Johnson, Linda Snetselaar, and Jennifer Robinson (University of Iowa, Iowa City/Davenport, IA); Lewis Kuller, Jane Cauley, and N. Carole Milas (University of Pittsburgh, Pittsburgh, PA); Karen C. Johnson, Suzanne Satterfield, Rongling Li, Stephanie Connelly, Fran Tylavsky (University of Tennessee Health Science Center, Memphis, TN); Sally Shumaker, Stephen Rapp, Claudine Legault, Mark Espeland, Laura Coker, and Michelle Naughton (Wake Forest University School of Medicine, Winston-Salem, NC).

Women's Health Initiative Memory Study: Sally Shumaker, Stephen Rapp, Claudine Legault, Mark Espeland, Laura Coker, and Michelle Naughton (Wake Forest University School of Medicine, Winston-Salem, NC).

Former Principal Investigators and Project Officers: Sylvia Wassertheil-Smoller (Albert Einstein College of Medicine, Bronx, NY); Haleh Sangi-Haghpeykar, Aleksandar Rajkovic, Jennifer Hays, and John Foreyt (Baylor College of Medicine, Houston, TX); Charles B. Eaton, Annlouise R. Assaf (Brown University, Providence, RI); Lawrence S. Phillips, Nelson Watts, Sally McNagny, and Dallas Hall (Emory University, Atlanta, GA); Shirley A.A. Beresford and Maureen Henderson (Fred Hutchinson Cancer Research Center, Seattle, WA); Lisa Martin, Judith Hsia, Valery Miller (George Washington University, Washington, DC); Rowan Chlebowski (Harbor-UCLA Research and Education Institute, Torrance, CA); Erin LeBlanc, Yvonne Michael, Evelyn Whitlock, Cheryl Ritenbaugh, and Barbara Valanis (Kaiser Permanente Center for Health Research, Portland, OR); Bette Caan and Robert Hiatt (Kaiser Permanente Division of Research, Oakland, CA); Carolyn Clifford (deceased) (National Cancer Institute, Bethesda, MD); Jane Morley Kotchen (Medical College of Wisconsin, Milwaukee, WI); Linda Pottern (National Heart, Lung, and Blood Institute, Bethesda, Maryland); Linda Van Horn and Philip Greenland (Northwestern University, Chicago/Evanston, IL); Lynda Powell, William Elliott, and Henry Black (Rush University Medical Center, Chicago, IL); Dorothy Lane and Iris Granek (State University of New York at Stony Brook, Stony Brook, NY); Maurizio Trevisan (University at Buffalo, Buffalo, NY); Cora E. Lewis and Albert Oberman (University of Alabama at Birmingham, Birmingham, AL).

Tamsen Bassford, Cheryl Ritenbaugh, and Tom Moon (University of Arizona, Tucson/Phoenix, AZ); John Robbins (University of California at Davis, Sacramento, CA); F. Allan Hubbell and Frank Meyskens, Jr. (University of California at Irvine, CA); Lauren Nathan and Howard Judd (deceased) (University of California at Los Angeles, CA); Robert D. Langer (University of California at San Diego, LaJolla/Chula Vista, CA); Michael Thomas, Margery Gass, and James Liu (University of Cincinnati, Cincinnati, OH); J. David Curb (deceased) (University of Hawaii, Honolulu, HI); Judith Ockene (University of Massachusetts/Fallon Clinic, Worcester, MA); Norman Lasser (University of Medicine and Dentistry of New Jersey, Newark, NJ); Mary Jo O'Sullivan and Marianna Baum (University of Miami, Miami, FL); Karen L. Margolis and Richard Grimm (University of Minnesota, Minneapolis, MN); Robert Brunner and Sandra Daugherty (deceased) (University of Nevada, Reno, NV); Gerardo Heiss, Barbara Hulka, and David Sheps (University of North Carolina, Chapel Hill, NC); Karen Johnson and William Applegate (University of Tennessee Health Science Center, Memphis, TN); Robert Brzyski and Robert Schenken (University of Texas Health Science Center, San Antonio, TX); Gloria E. Sarto and Catherine Allen (deceased) (University of Wisconsin, Madison, WI); Mara Vitolins, Denise Bonds, Electra Paskett, and Greg Burke (Wake Forest University School of Medicine, Winston-Salem, NC); Michael S. Simon and Susan Hendrix (Wayne State University School of Medicine/Karmanos Cancer Institute, Detroit, MI).

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