Britton Trabert1, Sally B Coburn2, Roni T Falk2, JoAnn E Manson3, Louise A Brinton2, Margery L Gass4, Lewis H Kuller5, Thomas E Rohan5,6, Ruth M Pfeiffer2, Lihong Qi7, Marcia L Stefanick8, Nicolas Wentzensen2, Garnet L Anderson9, Xia Xu10. 1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD, 20892-9768, USA. britton.trabert@nih.gov. 2. Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD, 20892-9768, USA. 3. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 4. Women's Health Institute, Cleveland Clinic, Cleveland, OH, USA. 5. Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA. 6. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA. 7. Public Health Sciences, School of Medicine, UC Davis, Sacramento, CA, USA. 8. Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. 9. Division of Public Health Sciences, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 10. Frederick National Laboratory for Cancer Research, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, MD, USA.
Abstract
PURPOSE: Menopausal hormone therapy (MHT) use induces alterations in circulating estrogens/estrogen metabolites, which may contribute to the altered risk of reproductive tract cancers among current users. Thus, the current study assessed associations between circulating estrogens/estrogen metabolites and ovarian and endometrial cancer risk among MHT users. METHODS: We conducted a nested case-control study among postmenopausal women using MHT at baseline in the Women's Health Initiative Observational Study (179 ovarian cancers, 396 controls; 230 endometrial cancers, 253 controls). Multivariable logistic regression was utilized to estimate odds ratios and 95% confidence intervals overall and by subtype. RESULTS: Estrogen/estrogen metabolite levels were not associated with overall or serous ovarian cancer risk, examined separately. However, unconjugated estradiol was positively associated with non-serous ovarian cancer risk [quintile 5 vs. quintile 1: 3.01 (1.17-7.73); p-trend = 0.03; p-het < 0.01]. Endometrial cancer risk was unrelated to estrogen/estrogen metabolite levels among women who took combined estrogen/progestin therapy (EPT). CONCLUSIONS: These findings provide novel evidence that may support a heterogeneous hormonal etiology across ovarian cancer subtypes. Circulating estrogens did not influence endometrial cancer risk among women with EPT-induced high-estrogen levels. Larger studies are needed to delineate the relationship between ovarian/endometrial cancer subtypes and estrogen levels in the context of MHT use.
PURPOSE: Menopausal hormone therapy (MHT) use induces alterations in circulating estrogens/estrogen metabolites, which may contribute to the altered risk of reproductive tract cancers among current users. Thus, the current study assessed associations between circulating estrogens/estrogen metabolites and ovarian and endometrial cancer risk among MHT users. METHODS: We conducted a nested case-control study among postmenopausal women using MHT at baseline in the Women's Health Initiative Observational Study (179 ovarian cancers, 396 controls; 230 endometrial cancers, 253 controls). Multivariable logistic regression was utilized to estimate odds ratios and 95% confidence intervals overall and by subtype. RESULTS:Estrogen/estrogen metabolite levels were not associated with overall or serous ovarian cancer risk, examined separately. However, unconjugated estradiol was positively associated with non-serous ovarian cancer risk [quintile 5 vs. quintile 1: 3.01 (1.17-7.73); p-trend = 0.03; p-het < 0.01]. Endometrial cancer risk was unrelated to estrogen/estrogen metabolite levels among women who took combined estrogen/progestin therapy (EPT). CONCLUSIONS: These findings provide novel evidence that may support a heterogeneous hormonal etiology across ovarian cancer subtypes. Circulating estrogens did not influence endometrial cancer risk among women with EPT-induced high-estrogen levels. Larger studies are needed to delineate the relationship between ovarian/endometrial cancer subtypes and estrogen levels in the context of MHT use.
Entities:
Keywords:
Current hormone therapy users; Endogenous estrogens; Endometrial cancer; Estrogen metabolites; Nested case–control study; Ovarian cancer
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