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"Risks and benefits of estrogen plus
progestin in healthy postmenopausal women. Principal results from
the Women's Health Initiative Randomized Controlled Trial,"
by the Writing Group for the Women's Health
Initiative Investigators (J.E. Rossouw, et al.), JAMA-Journal of the
American Medical Association, 288(3): 321-33,
17 July 2002.
[Authors' affiliations (Writing Group): 9
U.S. institutions]
Abstract: "Context Despite
decades of accumulated observational evidence, the balance of risks and
benefits for
hormone use in healthy postmenopausal women remains uncertain. Objective
To assess the major health benefits and risks of the most commonly used
combined hormone preparation 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 the 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 statistics for invasive
breast cancer exceeded the stopping boundary for this adverse effect and the
global index statistic supported risks exceeding 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, 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, 2.13-3.25) 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 10000 person-years attributable to estrogen plus progestin were 7
more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast
cancers, while absolute risk reductions per 10000 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 10000 person-years. Conclusions
Overall health risks exceeded benefits from use of combined estrogen plus
progestin for an average 5.2-year follow-up among healthy postmenopausal US
women. All-cause mortality was not affected during the trial. The 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."
This 2002 report from the Journal of the
American Medical Association was cited 164 times in current journal
articles indexed by Thomson ISI during January-February 2004. Thanks to its
latest two-month citation total, this
paper once again surpassed all others published in the last two years
(including reviews), topping the list of medicine's most cited for the eighth
bimonthly ranking in a row. Prior to the most recent count, citations to the
paper have accrued as follows:
November-December 2003: 128 citations
September-October 2003: 183
July-August 2003: 142
May-June 2003: 131
March-April 2003: 105
January-February 2003: 87
November-December 2002: 82
September-October 2002: 46
Total citations to date: 1,068
JoAnn Manson of the Women's Health Initiative answers a
few questions about this month's (June
2004) fast breaking paper in field of
Clinical Medicine: "Estrogen plus progestin and the risk of coronary heart disease."
SOURCE: Hot
Papers Database (Included with a subscription to the ISI print newsletter Science
Watch®, available from the ISI
Research Services Group. Packaged on a CD-ROM that is mailed with each Science
Watch issue, the Hot
Papers Database contains data on hundreds of highly cited papers published
during the last two years. User interface permits searching by author,
organization, journal, field, and more. Total citations, as well as citations
accrued during successive bimonthly periods, can be assessed and graphed. An
updated CD containing the most recent bimonthly data is mailed with every new
issue of Science
Watch,
six times a year. The CD also includes an electronic version of the Science
Watch
issue in HTML format, for personal desktop access.)
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