Association of hormonal and reproductive factors with differentiated thyroid cancer risk in women: a pooled prospective cohort analysis

Thomas J. O'Grady, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Sabina Rinaldi, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
Kara A. Michels, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Hans-Olov Adami, Clinical Effectiveness Group, Institute of Health and Society, University of Oslo, Oslo, Norway.
Julie E. Buring, Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Yu Chen, Division of Epidemiology, Department of Population Health and NYU Cancer Institute, NYU School of Medicine, New York, NY, USA.
Tess V. Clendenen, Division of Epidemiology, Department of Population Health and NYU Cancer Institute, NYU School of Medicine, New York, NY, USA.
Aimee D'Aloisio, Social & Scientific Systems, DLH Holdings Corporation, Durham, NC, USA.
Jessica Clague DeHart, School of Community and Global Health, Claremont Graduate University, Claremont, CA, USA.
Silvia Franceschi, Aviano Cancer Institute, IRCCS, Aviano, Italy.
Neal D. Freedman, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Gretchen L. Gierach, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Graham G. Giles, Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia.
James V. Lacey, Division of Health Analytics Department of Computational and Quantitative Medicine, Beckman Research Institute, City of Hope, Atlanta, GA, USA.
I-Min Lee, Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Linda M. Liao, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Martha S. Linet, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Marjorie L. McCullough, Department of Population Science, American Cancer Society, Atlanta, GA, USA.
Alpa V. Patel, Department of Population Science, American Cancer Society, Atlanta, GA, USA.
Anna Prizment, Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Kim Robien, Exercise and Nutrition Sciences, Milken Institute School of Public Health, George Washington University, Washington, DC, USA.
Dale P. Sandler, Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
Rachael Stolzenberg-Solomon, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Elisabete Weiderpass, International Agency for Research on Cancer (IARC/WHO), Lyon, France.
Emily White, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Alicja Wolk, Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Wei Zheng, Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
Amy Berrington de Gonzalez, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Cari M. Kitahara, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.

Document Type

Journal Article

Publication Date

12-18-2023

Journal

International journal of epidemiology

DOI

10.1093/ije/dyad172

Keywords

Thyroid cancer; hormone replacement therapy; hysterectomy; menarche; menopause; oophorectomy; oral contraceptives; parity

Abstract

BACKGROUND: The incidence of differentiated thyroid cancer (DTC) is higher in women than in men but whether sex steroid hormones contribute to this difference remains unclear. Studies of reproductive and hormonal factors and thyroid cancer risk have provided inconsistent results. METHODS: Original data from 1 252 907 women in 16 cohorts in North America, Europe, Australia and Asia were combined to evaluate associations of DTC risk with reproductive and hormonal factors. Multivariable-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: During follow-up, 2142 women were diagnosed with DTC. Factors associated with higher risk of DTC included younger age at menarche (<10 vs 10-11 years; HR, 1.28; 95% CI, 1.00-1.64), younger (<40; HR, 1.31; 95% CI, 1.05-1.62) and older (≥55; HR, 1.33; 95% CI, 1.05-1.68) ages at menopause (vs 40-44 years), ever use of menopausal hormone therapy (HR, 1.16; 95% CI, 1.02-1.33) and previous hysterectomy (HR, 1.25; 95% CI, 1.13-1.39) or bilateral oophorectomy (HR, 1.14; 95% CI, 1.00-1.29). Factors associated with lower risk included longer-term use (≥5 vs <5 years) of oral contraceptives (HR, 0.86; 95% CI, 0.76-0.96) among those who ever used oral contraception and baseline post-menopausal status (HR, 0.82; 95% CI, 0.70-0.96). No associations were observed for parity, duration of menopausal hormone therapy use or lifetime number of reproductive years or ovulatory cycles. CONCLUSIONS: Our study provides some evidence linking reproductive and hormonal factors with risk of DTC. Results should be interpreted cautiously considering the modest strength of the associations and potential for exposure misclassification and detection bias. Prospective studies of pre-diagnostic circulating sex steroid hormone measurements and DTC risk may provide additional insight.

Department

Exercise and Nutrition Sciences

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