Title

Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial

Authors

Garnet L. Anderson, Fred Hutchinson Cancer Research Center
Marian C. Limacher, University of Florida
Annlouise R. Assaf
Tamsen Bassford, University of Arizona
Shirley A. A. Beresford, University of Washington - Seattle Campus
Henry R. Black
Denise E. Bonds, University of Virginia - Main Campus
Robert L. Brunner, University of Nevada School of Medicine
Robert G. Brzyski, University of Texas at San Antonio
Bette Caan, Kaiser Permanente
Rowan T. Chlebowski, University of California - Davis
J. David Curb, University of Hawaii at Hilo
Margery Gass
Jennifer Hays, Baylor Medical College
Gerardo Heiss, University of North Carolina
Susan L. Hendrix
Barbara V. Howard, Medstar Research Institute
Judith Hsia, George Washington University
F. Allan Hubbell
Rebecca D. Jackson, The Ohio State University
Karen C. Johnson, University of Tennessee - Chattanooga
Howard Judd
Jane Morley Kotchen, Medical College of Wisconsin
Lewis H. Kuller, University of Pittsburgh - Main Campus
Andrea Z. LaCroix, University of Washington - Seattle Campus
Dorothy S. Lane, STATE UNIVERSITY OF NEW YORK S
Robert D. Langer, Geisinger Health System
Norman L. Lasser
Cora E. Lewis, University of Alabama - Birmingham
JoAnn E. Manson, Harvard Medical School
Karen L. Margolis, HealthPartners Research Foundation
Judith K. Ockene, University of Massachusetts Medical SchoolFollow
Mary Jo O'Sullivan
Lawrence Phillips
Ross L. Prentice, Fred Hutchinson Cancer Research Center
Cheryl Ritenbaugh, Kaiser Permanente Center for Health Research
John Robbins, University of California at Davis School of Medicine
Jacques E. Rossouw
Gloria E. Sarto, University of Wisconsin–Madison
Marcia L. Stefanick, Stanford University
Linda Van Horn, Northwestern University
Jean Wactawski-Wende, STATE UNIVERSITY OF NEW YORK S
Robert B. Wallace, University of Iowa
Sylvia Wassertheil-Smoller, Albert Einstein College of Medicine

UMMS Affiliation

Department of Medicine, Division of Preventive and Behavioral Medicine

Date

4-14-2004

Document Type

Article

Subjects

Aged; Breast Neoplasms; Cause of Death; Colorectal Neoplasms; Coronary Disease; Double-Blind Method; *Estrogen Replacement Therapy; Estrogens; Estrogens, Conjugated (USP); Female; Hip Fractures; Humans; *Hysterectomy; Middle Aged; Postmenopause; Proportional Hazards Models; Pulmonary Embolism; Risk Assessment; Stroke

Disciplines

Life Sciences | Medicine and Health Sciences | Women's Studies

Abstract

CONTEXT: Despite decades of use and considerable research, the role of estrogen alone in preventing chronic diseases in postmenopausal women remains uncertain.

OBJECTIVE: To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States.

DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled disease prevention trial (the estrogen-alone component of the Women's Health Initiative [WHI]) conducted in 40 US clinical centers beginning in 1993. Enrolled were 10 739 postmenopausal women, aged 50-79 years, with prior hysterectomy, including 23% of minority race/ethnicity.

INTERVENTION: Women were randomly assigned to receive either 0.625 mg/d of conjugated equine estrogen (CEE) or placebo.

MAIN OUTCOME MEASURES: The primary outcome was coronary heart disease (CHD) incidence (nonfatal myocardial infarction or CHD death). Invasive breast cancer incidence was the primary safety outcome. A global index of risks and benefits, including these primary outcomes plus stroke, pulmonary embolism (PE), colorectal cancer, hip fracture, and deaths from other causes, was used for summarizing overall effects.

RESULTS: In February 2004, after reviewing data through November 30, 2003, the National Institutes of Health (NIH) decided to end the intervention phase of the trial early. Estimated hazard ratios (HRs) (95% confidence intervals [CIs]) for CEE vs placebo for the major clinical outcomes available through February 29, 2004 (average follow-up 6.8 years), were: CHD, 0.91 (0.75-1.12) with 376 cases; breast cancer, 0.77 (0.59-1.01) with 218 cases; stroke, 1.39 (1.10-1.77) with 276 cases; PE, 1.34 (0.87-2.06) with 85 cases; colorectal cancer, 1.08 (0.75-1.55) with 119 cases; and hip fracture, 0.61 (0.41-0.91) with 102 cases. Corresponding results for composite outcomes were: total cardiovascular disease, 1.12 (1.01-1.24); total cancer, 0.93 (0.81-1.07); total fractures, 0.70 (0.63-0.79); total mortality, 1.04 (0.88-1.22), and the global index, 1.01 (0.91-1.12). For the outcomes significantly affected by CEE, there was an absolute excess risk of 12 additional strokes per 10 000 person-years and an absolute risk reduction of 6 fewer hip fractures per 10 000 person-years. The estimated excess risk for all monitored events in the global index was a nonsignificant 2 events per 10 000 person-years.

CONCLUSIONS: The use of CEE increases the risk of stroke, decreases the risk of hip fracture, and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years. A possible reduction in breast cancer risk requires further investigation. The burden of incident disease events was equivalent in the CEE and placebo groups, indicating no overall benefit. Thus, CEE should not be recommended for chronic disease prevention in postmenopausal women.

Rights and Permissions

Citation: JAMA. 2004 Apr 14;291(14):1701-12. Link to article on publisher's site

Related Resources

Link to article in PubMed

PubMed ID

15082697