Estrogen plus Progestin and Colorectal Cancer in Postmenopausal Women
Rowan T. Chlebowski, M.D., Ph.D., Jean Wactawski-Wende, Ph.D., Cheryl Ritenbaugh, Ph.D., M.P.H., F. Allan Hubbell, M.D., M.S.P.H., Joao Ascensao, M.D., Ph.D., Rebecca J. Rodabough, M.S., Carol A. Rosenberg, M.D., Victoria M. Taylor, M.D., M.P.H., Randall Harris, M.D., Ph.D., Chu Chen, Ph.D., Lucile L. Adams-Campbell, Ph.D., Emily White, Ph.D., for the Women's Health Initiative Investigators
Background Although the Women's Health Initiative (WHI) trialof estrogen plus progestin in postmenopausal women identifiedmore overall health risks than benefits among women in the hormonegroup, the use of estrogen plus progestin was associated witha significant decrease in the risk of colorectal cancer. Weanalyzed features of the colorectal cancers that developed andtheir relation to the characteristics of the participants.
Methods In the WHI trial, 16,608 postmenopausal women who were50 to 79 years of age and had an intact uterus were randomlyassigned to a combination of conjugated equine estrogens (0.625mg per day) plus medroxyprogesterone acetate (2.5 mg per day)or placebo. The main outcome measures were the incidence, stages,and types of colorectal cancer, as determined by blinded centraladjudication.
Results There were 43 invasive colorectal cancers in the hormonegroup and 72 in the placebo group (hazard ratio, 0.56; 95 percentconfidence interval, 0.38 to 0.81; P=0.003). The invasive colorectalcancers in the hormone group were similar in histologic featuresand grade to those in the placebo group but with a greater numberof positive lymph nodes (mean ±SD, 3.2±4.1 vs.0.8±1.7; P=0.002) and were more advanced (regional ormetastatic disease, 76.2 percent vs. 48.5 percent; P=0.004).In exploratory analyses, women in the hormone group with antecedentvaginal bleeding had colorectal cancers with a greater numberof positive nodes than women in the hormone group who did nothave vaginal bleeding (3.8±4.3 vs. 0.7±1.5 nodes,P=0.006).
Conclusions Relatively short-term use of estrogen plus progestinwas associated with a decreased risk of colorectal cancer. However,colorectal cancers in women who took estrogen plus progestinwere diagnosed at a more advanced stage than those in womenwho took placebo.
Source Information
From the Department of Medicine, Harbor–UCLA Research and Education Institute, Torrance, Calif. (R.T.C.); the Departments of Social and Preventive Medicine and Gynecology and Obstetrics, University of Buffalo, Buffalo, N.Y. (J.W.-W.); Kaiser Permanente Center for Health Research, Portland, Oreg. (C.R.); the Department of Medicine, University of California, Irvine (F.A.H.); the Department of Medicine, Division of Hematology–Oncology, George Washington University, Washington, D.C. (J.A.); the Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle (R.J.R., V.M.T., C.C., E.W.); the Department of Internal Medicine, Evanston Northwestern Healthcare, Evanston, Ill. (C.A.R.); the College of Medicine and Public Health, Ohio State University, Columbus (R.H.); and the Department of Medicine, Howard University Cancer Center, Washington, D.C. (L.L.A.-C.).
Address reprint requests to Dr. Chlebowski at Harbor–UCLA Research and Education Institute, 1124 W. Carson St., Torrance, CA 90502, or at rchlebowski{at}rei.edu.
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