Reproductive factors and postmenopausal hormone use in relation to endometrial cancer risk in the Nurses' Health Study cohort 1976–2004

Authors

  • Stalo Karageorgi,

    Corresponding author
    1. Department of Environmental Health, Harvard School of Public Health, Boston, MA
    2. Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, MA
    • Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA
    Search for more papers by this author
    • Fax: +617-432-1722

  • Susan E. Hankinson,

    1. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
    2. Department of Epidemiology, Harvard School of Public Health, Boston, MA
    Search for more papers by this author
  • Peter Kraft,

    1. Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, MA
    2. Department of Epidemiology, Harvard School of Public Health, Boston, MA
    Search for more papers by this author
  • Immaculata De Vivo

    1. Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, MA
    2. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
    3. Department of Epidemiology, Harvard School of Public Health, Boston, MA
    Search for more papers by this author

Abstract

Endometrial cancer is a disease primarily driven by cumulative exposure to estrogen unopposed by progesterone. Reproductive factors associated with changes in endogenous hormone levels and use of exogenous hormones such as postmenopausal hormones influence the risk of disease. The authors used the Nurses' Health Study, comprised of 121,700 nurses, to assess the above associations. Over 28 years of follow-up, 778 adenocarcinoma cases were diagnosed and 1,850,078 person-years were accumulated. Cox proportional hazards models were used to estimate relative risks (RR) and 95% confidence intervals (CI). A late age at menarche decreased the risk independent of body mass index (BMI) (P-trend = 0.02). A late age at menopause increased cancer risk (P-trend = 0.0003). An advanced age at last birth reduced the risk (P-trend < 0.0001), however, an inverse association with age at first birth and parity diminished after adjustment for age at last birth. Compared with never users, an increased risk was observed among long-term (≥5 years) users of both estrogen (E) (RR = 7.67, 95% CI: 5.57, 10.57) and combined estrogen plus progesterone (E+P) (RR = 1.52, 95% CI: 1.03, 2.23). Normal-weight (BMI < 25) women had the highest risk following E or E+P use (P-interaction-E = 0.0008, P-interaction-E+P = 0.02). The findings from this study underscore the importance of hormonal mechanisms in endometrial carcinogenesis.

Ancillary