Source: JAMA, The Journal of the American Medical Association, August 13, 1997 v278 n6 p477(1). Title: Venous thromboembolic events associated with hormone replacement therapy.(Letter to the Editor) Author: Deborah Grady, Stephen B. Hulley and Curt Furberg Subjects: Hormone therapy - Adverse and side effects Thromboembolism - Risk factors Postmenopausal women - Health aspects Magazine Collection: 90C5015 Electronic Collection: A19697500 RN: A19697500
To the Editor. -- the Heart and Estrogen-Progestin Replacement Study (HERS) is a randomized, double-blind, placebo-controlled trial designed to test the effect of hormone replacement therapy on the rate of new coronary heart disease (CHD) events in 2763 postmenopausal women younger than 80 years who had preexisting CHD and an intact uterus at enrollment. Participants were randomly assigned to take 1 tablet daily, either a placebo or the combination of 0.625 mg of conjugated equine estrogens and 2.5 mg of medroxyprogesterone acetate. Recruitment for HERS was completed in September 1994, and the trial is scheduled to continue until mid 1998.
In addition to the primary end point of CHD events, a number of secondary end points were specified in the HERS protocol for evaluation in planned interim monitoring; these include the occurrence of venous thromboembolic events (VTE), ie, deep vein thrombosis, pulmonary embolism, or both.
Recently, 4 observational studies[1-4] and 1 trial were published that provided evidence for an association between postmenopausal hormone therapy and VTE. In those studies, the risk of VTE among current users of hormone replacement therapy was 2 to 3.6 times higher than the risk among non-users. With more than three quarters of follow-up completed, there is an increased relative risk of VTE among HERS participants taking hormone replacement therapy compared with those taking placebo (nominal P=.002, which is outside the Lan and DeMets interim monitoring boundary), and the magnitude of this relative risk is consistent with the findings from the epidemiologic studies. We have followed the HERS Data and Safety Monitoring Board recommendation that these interim findings be reported to both HERS participants and to the medical community. Once the HERS study concludes, it will provide additional information about the overall benefit-to-risk profile of hormone replacement therapy in women with coronary disease.
Deborah Grady, MD, MPH
Stephen B. Hulley, MD
University of California, San Francisco
Curt Furberg, MD
Bowman Gray School of Medicine
[1.] Daly E, Vessey MP, Hawkins MM, Carson JL, Gough P, Marsh S. Risk of venous thromboembolism in users of hormone replacement therapy. Lancet. 1996;348: 977-980.
[2.] Jick H, Derby LE, Myers MW, Vasilakis C, Newton KM. Risk of hospital admission for idiopathic venous thromboembolism among users of postmenopausal oestrogens. Lancet. 1996;348:981-983.
[3.] Grodstein F, Stampfer MJ, Goldhaber SZ, et al. Prospective study of exogenous hormones and risk of pulmonary embolism in women. Lancet. 1996;348:983-987.
[4.] Gutthann S, Rodriguez L, Castellsague J, Ollart A. Hormone replacement therapy and risk of venous thromboembolism: population based case-control study. BMJ. 1997;314:796-800.
[5.] The Writing Group for the PEPI Trial. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women: the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA. 1995;273:199-208.
[6.] Lan KKG, DeMets DL. Discrete sequential boundaries for clinical trials. Biometrika. 1983;70:649-653.
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