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American Journal of Epidemiology Advance Access originally published online on September 22, 2006
American Journal of Epidemiology 2006 164(8):775-786; doi:10.1093/aje/kwj316
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American Journal of Epidemiology Copyright © 2006 by the Johns Hopkins Bloomberg School of Public Health All rights reserved; printed in U.S.A.

Original Contribution

Case-Control Study of Postmenopausal Hormone Replacement Therapy and Endometrial Cancer

Brian L. Strom1,2,3,4,5, Rita Schinnar3, Anita L. Weber3, Greta Bunin3,5,6, Jesse A. Berlin7, Mona Baumgarten8, Angela DeMichele1,2,3,5, Stephen C. Rubin5,9, Michelle Berlin10, Andrea B. Troxel2,3,5 and Timothy R. Rebbeck2,3,5

1 Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia, PA
2 Department of Biostatistics and Epidemiology, School of Medicine, University of Pennsylvania, Philadelphia, PA
3 Center for Clinical Epidemiology and Biostatistics, School of Medicine, University of Pennsylvania, Philadelphia, PA
4 Center for Education and Research in Therapeutics, School of Medicine, University of Pennsylvania, Philadelphia, PA
5 The Abramson Cancer Center, Children's Hospital of Philadelphia, Philadelphia, PA
6 Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA
7 Pharmaceutical Research and Development, Johnson & Johnson, Titusville, NJ
8 Department of Epidemiology and Preventive Medicine, School of Medicine, University of Maryland, Baltimore, MD
9 Department of Obstetrics and Gynecology, School of Medicine, University of Pennsylvania, Philadelphia, PA
10 Center for Women's Health and Departments of Obstetrics and Gynecology, Public Health, and Preventive Medicine, Oregon Health and Science University, Portland, OR

Correspondence to Dr. Brian L. Strom, Center for Clinical Epidemiology and Biostatistics, School of Medicine, University of Pennsylvania, 824 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021 (e-mail: bstrom{at}cceb.med.upenn.edu).

This study evaluated recent inconsistent findings that adding progestins to postmenopausal estrogen replacement therapy protects against endometrial cancer. Using a population-based case-control study, the authors compared 511 endometrial cancer cases aged 50–79 years in the Philadelphia, Pennsylvania, region during 1999–2002 with 1,412 random-digit-dialing controls regarding postmenopausal hormone replacement therapy (HRT) use. Telephone interviews were performed with memory aids mailed in advance. An increased risk of endometrial cancer was observed among postmenopausal women using only unopposed estrogen for 3 or more years, compared with women who never used HRT (adjusted odds ratio = 3.4, 95% confidence interval (CI): 1.4, 8.3). Using combination HRT (of any duration) was associated with a substantial reduction in risk (odds ratio = 0.8, 95% CI: 0.6, 1.1). Comparing women using only combined estrogen and progestin for 3 or more years with women using only unopposed estrogen for 3 or more years, the authors found that the adjusted odds ratio was 0.2 (95% CI: 0.1, 0.6). Long-term use of unopposed estrogen is associated with increased risk for endometrial cancer, whereas combined estrogen plus progestin hormone therapy is not. Thus, if HRT is to be used in women with an intact uterus, this study confirms the benefit of adding progestins to the regimen.

case-control studies; endometrial neoplasms; estrogens; hormone replacement therapy; progestins

Abbreviations: CHRT, combination estrogen and progestin; CI, confidence interval; ERT, estrogen replacement therapy; HRT, hormone replacement therapy; OR, odds ratio


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