Early pregnancy sex steroids and maternal risk of epithelial ovarian cancer

    1. Eva Lundin2,10
    1. 1Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 280, Heidelberg 69120, Germany
      2Department of Medical Biosciences, Umeå University, Umeå, Sweden
      3Unit of Sexual and Reproductive Health, National Institute for Health and Welfare, Oulu, Finland
      4Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, New York, USA
      5New York University Cancer Institute, New York University School of Medicine, New York, New York, USA
      6Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland
      7School of Health Sciences, University of Tampere, Tampere, Finland
      8Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, USA
      9Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
      10Public Health and Clinical Medicine: Nutritional Research, Umeå University, Umeå, Sweden
    1. Correspondence should be addressed to H Schock; Email: h.schock{at}dkfz.de


    Well-established associations between reproductive characteristics and epithelial ovarian cancer (EOC) support an involvement of sex steroid hormones in the etiology of EOC. Limited previous studies have evaluated circulating androgens and the risk of EOC, and estrogens and progesterone have been investigated in only one of the previous studies. Furthermore, there is little data on potential heterogeneity in the association between circulating hormones and EOC by histological subgroup. Therefore, we conducted a nested case–control study within the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort to investigate the associations between circulating pre-diagnostic sex steroid concentrations and the histological subtypes of EOC. We identified 1052 EOC cases among cohort members diagnosed after recruitment (1975–2008) and before March 2011. Up to three controls were individually matched to each case (n=2694). Testosterone, androstenedione, 17-hydroxyprogesterone (17-OHP), progesterone, estradiol (E2), and sex hormone-binding globulin levels were measured in serum samples collected during the last pregnancy before EOC diagnosis. We used conditional logistic regression to estimate odds ratios (ORs) and 95% CIs. Associations between hormones and EOC differed with respect to tumor histology and invasiveness. Sex steroid concentrations were not associated with invasive serous tumors; however, doubling of testosterone and 17-OHP concentration was associated with approximately 40% increased risk of borderline serous tumors. A doubling of androgen concentrations was associated with a 50% increased risk of mucinous tumors. The risk of endometrioid tumors increased with higher E2 concentrations (OR: 1.89 (1.20–2.98)). This large prospective study in pregnant women supports a role of sex steroid hormones in the etiology of EOC arising in the ovaries.

    • Received 25 August 2014
    • Accepted 1 September 2014
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