Alice W Lee1, Anna H Wu1, Ashley Wiensch2, Bhramar Mukherjee2,3, Kathryn L Terry4,5, Holly R Harris6,7, Michael E Carney8, Allan Jensen9, Daniel W Cramer4,5, Andrew Berchuck10, Jennifer Anne Doherty11, Francesmary Modugno12,13,14, Marc T Goodman15,16, Aliya Alimujiang2, Mary Anne Rossing6,7, Kara L Cushing-Haugen6, Elisa V Bandera17, Pamela J Thompson15, Susanne K Kjaer9,18, Estrid Hogdall9,19, Penelope M Webb20, David G Huntsman21,22,23,24, Kirstin B Moysich25, Galina Lurie26, Roberta B Ness27, Daniel O Stram28, Lynda Roman29, Malcolm C Pike28,30, Celeste Leigh Pearce28,2. 1. From the Department of Public Health, California State University, Fullerton, Fullerton, CA. 2. Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI. 3. Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI. 4. Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, Boston, MA. 5. Harvard T.H. Chan School of Public Health, Boston, MA. 6. Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA. 7. Department of Epidemiology, University of Washington, Seattle, WA. 8. Department of Obstetrics and Gynecology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI. 9. Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark. 10. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University School of Medicine, Durham, NC. 11. Huntsman Cancer Institute, Department of Population Health Sciences, University of Utah, Salt Lake City, UT. 12. Ovarian Cancer Center of Excellence, Womens Cancer Research Program, Magee-Womens Research Institute and Hillman Cancer Center, Pittsburgh, PA. 13. Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA. 14. Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA. 15. Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA. 16. Community and Population Health Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA. 17. Cancer Prevention and Control Program, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ. 18. Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 19. Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark. 20. Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. 21. Department of Molecular Oncology, BC Cancer Research Centre, Vancouver, BC, Canada. 22. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada. 23. OVCARE, Vancouver Coastal Health Research Centre, Vancouver General Hospital and University of British Columbia, Vancouver, BC, Canada. 24. Department of Obstetrics and Gyencology, University of British Columbia, Vancouver, BC, Canada. 25. Division of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY. 26. Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI. 27. University of Texas School of Public Health, Houston, TX. 28. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA. 29. Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Keck School of Medicine, University of Southern California, Los Angeles, CA. 30. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.
Abstract
BACKGROUND: Menopausal estrogen-alone therapy is a risk factor for endometrial and ovarian cancers. When a progestin is included with the estrogen daily (continuous estrogen-progestin combined therapy), there is no increased risk of endometrial cancer. However, the effect of continuous estrogen-progestin combined therapy on risk of ovarian cancer is less clear. METHODS: We pooled primary data from five population-based case-control studies in the Ovarian Cancer Association Consortium, including 1509 postmenopausal ovarian cancer cases and 2295 postmenopausal controls. Information on previous menopausal hormonal therapy use, as well as ovarian cancer risk factors, was collected using in-person interviews. Logistic regression was used to assess the association between use of continuous estrogen-progestin combined therapy and risk of ovarian cancer by duration and recency of use and disease histotype. RESULTS: Ever postmenopausal use of continuous estrogen-progestin combined therapy was not associated with increased risk of ovarian cancer overall (OR = 0.85, 95% CI = 0.72, 1.0). A decreased risk was observed for mucinous ovarian cancer (OR = 0.40, 95% CI = 0.18, 0.91). The other main ovarian cancer histotypes did not show an association (endometrioid: OR = 0.86, 95% CI = 0.57, 1.3, clear cell: OR = 0.68, 95% CI = 0.40, 1.2; serous: OR = 0.98, 95% CI = 0.80, 1.2). CONCLUSIONS: Given that estrogen-alone therapy has been shown to be associated with increased risk of ovarian cancer, these findings are consistent with the hypothesis that adding a progestin each day ameliorates the carcinogenic effects of estrogen on the cells of origin for all histotypes of ovarian cancer.
BACKGROUND: Menopausal estrogen-alone therapy is a risk factor for endometrial and ovarian cancers. When a progestin is included with the estrogen daily (continuous estrogen-progestin combined therapy), there is no increased risk of endometrial cancer. However, the effect of continuous estrogen-progestin combined therapy on risk of ovarian cancer is less clear. METHODS: We pooled primary data from five population-based case-control studies in the Ovarian Cancer Association Consortium, including 1509 postmenopausal ovarian cancer cases and 2295 postmenopausal controls. Information on previous menopausal hormonal therapy use, as well as ovarian cancer risk factors, was collected using in-person interviews. Logistic regression was used to assess the association between use of continuous estrogen-progestin combined therapy and risk of ovarian cancer by duration and recency of use and disease histotype. RESULTS: Ever postmenopausal use of continuous estrogen-progestin combined therapy was not associated with increased risk of ovarian cancer overall (OR = 0.85, 95% CI = 0.72, 1.0). A decreased risk was observed for mucinous ovarian cancer (OR = 0.40, 95% CI = 0.18, 0.91). The other main ovarian cancer histotypes did not show an association (endometrioid: OR = 0.86, 95% CI = 0.57, 1.3, clear cell: OR = 0.68, 95% CI = 0.40, 1.2; serous: OR = 0.98, 95% CI = 0.80, 1.2). CONCLUSIONS: Given that estrogen-alone therapy has been shown to be associated with increased risk of ovarian cancer, these findings are consistent with the hypothesis that adding a progestin each day ameliorates the carcinogenic effects of estrogen on the cells of origin for all histotypes of ovarian cancer.
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