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Principal Results From the Women's
Health Initiative Randomized Controlled Trial
Writing Group for the Women's Health Initiative Investigators JAMA. 2002;288:321-333.
Context Despite decades of accumulated observational
evidence, the balance of risks and benefits for hormone use
(Hormone Replacement Therapy) in healthy postmenopausal women remains uncertain.
Objective To assess the major health benefits and
risks of the most commonly used
combined hormone preparation (HRT)
in the United States.
Design Estrogen plus progestin component of the Women's
Health Initiative, a randomized controlled primary
prevention trial (planned duration, 8.5 years) in which
16608 postmenopausal women aged 50-79 years with an
intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998.
Interventions Participants received conjugated equine
estrogens, 0.625 mg/d, plus medroxyprogesterone acetate,
2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102).
Main Outcomes Measures The primary outcome was
coronary heart disease (CHD) (nonfatal myocardial infarction
and
CHD death), with invasive
breast cancer as the
primary adverse outcome. A global index summarizing
the balance of risks and benefits included the 2 primary
outcomes plus stroke, pulmonary embolism (PE),
endometrial
cancer,
colorectal cancer, hip fracture, and death
due to other causes.
Results
On May 31, 2002, after a mean of
5.2 years of follow-up,
the
data and safety monitoring board
recommended stopping the trial of estrogen
plus progestin vs placebo because
the test statistic for invasive
breast cancer
exceeded the stopping boundary
for this adverse effect and the global
index statistic supported
HRT risks exceeding HRT benefits.
This
report includes data on the major clinical outcomes
through April 30, 2002.
Estimated hazard ratios (HRs) (nominal
95%
confidence intervals [CIs])
were as follows: CHD (Coronary
Heart Disease), 1.29 (1.02-1.63)
with 286 cases;
breast cancer, 1.26
(1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85)
with 212 cases;
PE, 2.13 (1.39-3.25) with 101 cases;
colorectal
cancer, 0.63 (0.43-0.92)
with 112 cases;
endometrial cancer,
0.83 (0.47-1.47) with 47 cases; hip
fracture, 0.66 (0.45-0.98) with 106 cases;
and death due to other
causes, 0.92 (0.74-1.14) with 331
cases.
Corresponding
HRs (nominal 95% CIs) for
composite outcomes were 1.22
(1.09-1.36) for total
cardiovascular
disease (arterial and venous disease), 1.03
(0.90-1.17) for total
cancer,
0.76 (0.69-0.85) for combined fractures,
0.98 (0.82-1.18) for total
mortality, and 1.15 (1.03-1.28) for the global
index. Absolute excess risks per 10 000 person-years
attributable to estrogen plus progestin were
7 more CHD (Coronary
Heart Disease) events, 8 more strokes,
8 more PEs, and 8 more
invasive
breast cancers, while absolute risk
reductions per 10 000 person-years
were 6 fewer
colorectal cancers
and 5 fewer hip fractures.
The absolute excess
risk of events included in the global
index was 19 per 10
000 person-years.
Conclusions Overall health risks
of Hormone Replacement Thrapy exceeded benefits
from use of combined estrogen plus progestin
(HRT) for an
average 5.2-year follow-up among healthy postmenopausal
US women. All-cause mortality was not affected during
the trial. The HRT risk-benefit profile found in this trial
is not consistent with the requirements for a viable
intervention for primary prevention of chronic diseases,
and the results indicate that this regimen should not
be initiated or continued for primary prevention of CHD
(Coronary Heart
Disease).
Writing Group for the Women's Health Initiative
Investigators: Jacques E. Rossouw, MBChB, MD, National
Heart, Lung, and Blood Institute, Bethesda, Md; Garnet
L. Anderson, PhD, Ross L. Prentice, PhD, Andrea Z.
LaCroix, PhD, and Charles Kooperberg, PhD, Fred Hutchinson
Cancer Research Center, Seattle, Wash; Marcia L.
Stefanick, PhD, Stanford University Clinical Center,
Stanford, Calif; Rebecca D. Jackson, MD, Ohio State
University Clinical Center, Columbus; Shirley A.
A. Beresford, PhD, Fred Hutchinson Cancer Research
Center, Seattle, Wash; Barbara V. Howard, PhD, MedStar
Research Institute, Washington, DC; Karen C. Johnson,
MD, MPH, University of Tennessee, Memphis; Jane Morley
Kotchen, MD, Medical College of Wisconsin, Milwaukee;
Judith Ockene, PhD, University of Massachusetts Medical
School, Worcester.
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