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Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin
Journal article   Open access   Peer reviewed

Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin

Gerardo Heiss, Robert Wallace, Garnet L. Anderson, Aaron Aragaki, Shirley A. A. Beresford, Robert Brzyski, Rowan T. Chlebowski, Margery Gass, Andrea LaCroix, Joann E. Manson, …
JAMA : the journal of the American Medical Association, Vol.299(9), pp.1036-1045
03/05/2008
DOI: 10.1001/jama.299.9.1036
PMID: 18319414
url
https://doi.org/10.1001/jama.299.9.1036View
Published (Version of record) Open Access

Abstract

Context The Women's Health Initiative ( WHI) trial of estrogen plus progestin vs placebo was stopped early, after a mean 5.6 years of follow- up, because the overall health risks of hormone therapy exceeded its benefits. Objective To report health outcomes at 3 years ( mean 2.4 years of follow- up) after the intervention was stopped. Design, Setting, and Participants The intervention phase was a double- blind, placebo- controlled, randomized trial of conjugated equine estrogens ( CEE) 0.625 mg daily plus medroxyprogesterone acetate ( MPA) 2.5 mg daily, in 16 608 women aged 50 through 79 years, recruited by 40 centers from 1993 to 1998. The postintervention phase commenced July 8, 2002, and included 15 730 women. Main Outcome Measures Semi- annual monitoring and outcomes ascertainment continued per trial protocol. The primary end points were coronary heart disease and invasive breast cancer. A global index summarizing the balance of risks and benefits included the 2 primary end points plus stroke, pulmonary embolism, endometrial cancer, colorectal cancer, hip fracture, and death due to other causes. Results The risk of cardiovascular events after the intervention was comparable by initial randomized assignments, 1.97% ( annualized rate) in the CEE plus MPA ( 343 events) and 1.91% in the placebo group ( 323 events). A greater risk of malignancies occurred in the CEE plus MPA than in the placebo group ( 1.56% [ n= 281] vs 1.26% [ n= 218]; hazard ratio [ HR], 1.24; 95% confidence interval [ CI], 1.04- 1.48). More breast cancers were diagnosed in women who had been randomly assigned to receive CEE plus MPA vs placebo ( 0.42% [ n= 79] vs 0.33% [ n= 60]; HR, 1.27; 95% CI, 0.91- 1.78) with a modest trend toward a lower HR during the follow- up after the intervention. All- cause mortality was somewhat higher in the CEE plus MPA than in the placebo group ( 1.20% [ n= 233] vs 1.06% [ n= 196]; HR, 1.15; 95% CI, 0.95- 1.39). The global index of risks and benefits was unchanged from randomization through March 31, 2005 ( HR, 1.12; 95% CI, 1.03- 1.21), indicating that the risks of CEE plus MPA exceed the benefits for chronic disease prevention. Conclusions The increased cardiovascular risks in the women assigned to CEE plus MPA during the intervention period were not observed after the intervention. A greater risk of fatal and nonfatal malignancies occurred after the intervention in the CEE plus MPA group and the global risk index was 12% higher in women randomly assigned to receive CEE plus MPA compared with placebo. Trial Registration clinicaltrials. gov Identifier: NCT00000611.
 General & Internal Medicine Life Sciences & Biomedicine Medicine, General & Internal Science & Technology

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