Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial
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.
Suggested Citation
Garnet L. Anderson, Marian C. Limacher, Annlouise R. Assaf, Tamsen
Bassford, Shirley A. A. Beresford, Henry R. Black, Denise E. Bonds,
Robert L. Brunner, Robert G. Brzyski, Bette Caan, Rowan T. Chlebowski,
David Curb, Margery Gass, Jennifer Hays, Gerardo Heiss, Susan L.
Hendrix, Barbara V. Howard, Judith Hsia, F. Allan Hubbell, Rebecca D.
Jackson, Karen C. Johnson, Howard Judd, Jane Morley Kotchen, Lewis H.
Kuller, Andrea Z. LaCroix, Dorothy S. Lane, Robert D. Langer, Norman L.
Lasser, Cora E. Lewis, JoAnn E. Manson, Karen L. Margolis, Judith K.
Ockene, Mary Jo O'Sullivan, Lawrence Phillips, Ross L. Prentice, Cheryl
Ritenbaugh, John Robbins, Jacques E. Rossouw, Gloria E. Sarto, Marcia L.
Stefanick, Linda Van Horn, Jean Wactawski-Wende, Robert B. Wallace, and
Sylvia Wassertheil-Smoller. "Effects of conjugated equine estrogen in
postmenopausal women with hysterectomy: the Women's Health Initiative
randomized controlled trial" JAMA : the journal of the American Medical Association 291.14 (2004).
Available at: http://works.bepress.com/ockenej/55
Available at: http://works.bepress.com/ockenej/55
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