BACKGROUND: Female sex hormones are known to have immunomodulatory effects. Therefore, reproductive factors and exogenous hormone use could influence the risk of multiple myeloma in women. However, the role of hormonal factors in multiple myeloma etiology remains unclear because previous investigations were underpowered to detect modest associations. METHODS: We conducted a pooled analysis of seven case-control studies included in the International Multiple Myeloma Consortium, with individual data on reproductive factors and exogenous hormone use from 1,072 female cases and 3,541 female controls. Study-specific odds ratios and corresponding 95% confidence intervals (CI) were estimated using logistic regression and pooled analyses were conducted using random effects meta-analyses. RESULTS: Multiple myeloma was not associated with reproductive factors, including ever parous [OR = 0.92; 95% confidence interval (CI), 0.68-1.25], or with hormonal contraception use (OR = 1.04; 95% CI, 0.80-1.36). Postmenopausal hormone therapy users had nonsignificantly reduced risks of multiple myeloma compared with never users, but this association differed across centers (OR = 0.65; 95% CI, 0.37-1.15, I(2) = 76.0%, Pheterogeneity = 0.01). CONCLUSIONS: These data do not support a role for reproductive factors or exogenous hormones in myelomagenesis. IMPACT: Incidence rates of multiple myeloma are higher in men than in women, and sex hormones could influence this pattern. Associations with reproductive factors and exogenous hormone use were inconclusive despite our large sample size, suggesting that female sex hormones may not play a significant role in multiple myeloma etiology.

Biological Hematology Unit CRB Ferdinand Cabanne Universitary Hospital of Dijon and EA4184 University of Burgundy Dijon France

Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute and MF MU Brno Czech Republic

Center for Chronic Immunodeficiency Molecular Epidemiology University Medical Center Freiburg Freiburg Germany

Channing Division of Network Medicine Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts

Department of Cancer Prevention and Control Roswell Park Cancer Institute Buffalo New York

Department of Environmental and Occupational Health Drexel University School of Public Health Philadelphia Pennsylvania

Department of Epidemiology University of Alabama at Birmingham Birmingham Alabama

Department of Internal Medicine University of Iowa Iowa City Iowa

Department of Pathology University of Alabama at Birmingham University of Alabama at Birmingham Comprehensive Cancer Center Birmingham Alabama

Department of Public Health Clinical and Molecular Medicine Occupational Health Section University of Cagliari Cagliari Italy

Division of Cancer Epidemiology and Genetics NCI NIH DHHS Rockville Maryland

Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany

Division of Cancer Etiology Department of Population Sciences City of Hope and Beckman Research Institute Duarte California

Division of Hematology and Hematologic Malignancies University of Utah School of Medicine and Huntsman Cancer Institute Salt Lake City Utah

IARC International Agency for Research on Cancer Lyon France

Public Health University College Dublin Ireland

Tisch Cancer Institute and Institute for Translational Epidemiology Icahn School of Medicine at Mount Sinai New York New York

Unit of Infections and Cancer Cancer Epidemiology Research Programme IDIBELL Catalan Institute of Oncology Barcelona Spain Department of Medicine University of Barcelona Barcelona Spain CIBER Epidemiologia y Salud Pública Madrid Spain

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