title: Levonorgestrel-releasing intrauterine system and the risk of breast cancer: A nationwide cohort study.
abstract: BACKGROUND
  Prolonged steroid hormone therapy increases the risk of breast cancer, especially the risk of lobular cancer, but the effect of the levonorgestrel-releasing intrauterine system (LNG-IUS) use is controversial. In this study we aimed to test the hypothesis that risk for lobular breast cancer is elevated among LNG-IUS users.
  
  
  METHODS
  We identified from the national Medical Reimbursement Registry of Finland the women aged 30-49 who had used LNG-IUS for the treatment or prevention of menorrhagia in 1994-2007, and from the Finnish Cancer Registry breast cancers diagnosed before the age of 55 and by the end of 2012.
  
  
  RESULTS
  A total of 2015 women had breast cancer diagnosed in a cohort of 93 843 LNG-IUS users during follow-up consisting of 1 032 767 women-years. The LNG-IUS users had an increased risk for both ductal breast cancer [standardized incidence ratio (SIR) 1.20, 95% confidence interval (CI) 1.14-1.25] and for lobular breast cancer (SIR 1.33, 95% CI 1.20-1.46), as compared with the general female population. The highest risk was found in LNG-IUS users who purchased the device at least twice, whose SIR for lobular cancer was 1.73 (95% CI 1.37-2.15).
  
  
  CONCLUSIONS
  The results imply that intrauterine administration of levonorgestrel is not only related to an excess risk of lobular breast cancer but also, in contrary to previous assumptions, to an excess risk of ductal breast cancer.
authors.affiliation: a Department of Obstetrics and Gynecology , Hyvinkää Hospital , Hyvinkää , Finland.
authors.forename: Tuuli
authors.initials: T
authors.lastname: Soini
authors.affiliation: b Department of Obstetrics and Gynecology , Hyvinkää Hospital , Hyvinkää , Finland.
authors.forename: Ritva
authors.initials: R
authors.lastname: Hurskainen
authors.affiliation: c Department of Obstetrics and Gynecology , Turku University Hospital , Turku , Finland.|d University of Turku , Turku , Finland.
authors.forename: Seija
authors.initials: S
authors.lastname: Grénman
authors.affiliation: e School of Medicine, University of Tampere, University of Tampere , Finland.|f Department of Obstetrics and Gynecology , Tampere University Hospital , Tampere , Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Mäenpää
authors.affiliation: g Department of Obstetrics and Gynecology , Helsinki University Hospital , Helsinki , Finland.|h University of Helsinki , Helsinki , Finland.
authors.forename: Jorma
authors.initials: J
authors.lastname: Paavonen
authors.affiliation: i Department of Oncology , Comprehensive Cancer Center, Helsinki University Hospital , Helsinki , Finland.|j Department of Oncology , University of Helsinki , Helsinki , Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Joensuu
authors.affiliation: k School of Health Sciences, University of Tampere, University of Tampere , Finland.|l Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research , Helsinki , Finland.
authors.forename: Eero
authors.initials: E
authors.lastname: Pukkala
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D018270:Carcinoma, Ductal, Breast / Q000139:chemically induced / Q000453:epidemiology; D018275:Carcinoma, Lobular / Q000139:chemically induced / Q000453:epidemiology; D015331:Cohort Studies; D003271:Contraceptive Agents, Female / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D006801:Humans; D007436:Intrauterine Devices, Medicated / Q000009:adverse effects; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000009:adverse effects*; D008875:Middle Aged
chemical_list: D003271:Contraceptive Agents, Female; D016912:Levonorgestrel