Cancer Risk in Women Using the Levonorgestrel-Releasing Intrauterine System in Finland

Soini, Tuuli MD; Hurskainen, Ritva MD; Grénman, Seija MD; Mäenpää, Johanna MD; Paavonen, Jorma MD; Pukkala, Eero PhD

doi: 10.1097/AOG.0000000000000356
Contents: Original Research

OBJECTIVE: To examine the association between premenopausal use of the levonorgestrel-releasing intrauterine system and cancer incidence in Finland with a special focus on endometrial adenocarcinoma.

METHODS: All Finnish women aged 30–49 years using a levonorgestrel-releasing intrauterine system for treatment of menorrhagia in 1994–2007 (n=93,843) were identified from the National Reimbursement Registry and linked to the Finnish Cancer Registry data. The incidence of cancers in levonorgestrel-releasing intrauterine system users was compared with that in the general population.

RESULTS: A total of 2,781 cancer cases were detected in levonorgestrel-releasing intrauterine system users during the follow-up of 855,324 women-years. The standardized incidence ratio (observed-to-expected ratio) for endometrial adenocarcinoma was 0.50 (95% confidence interval [CI] 0.35–0.70; 34 observed compared with 68 expected cases) after the first levonorgestrel-releasing intrauterine system purchase and 0.25 (95% CI 0.05–0.73; three observed compared with 12 expected cases) after two purchases. The standardized incidence ratio for ovarian cancer was 0.60 (95% CI 0.45–0.76; 59 observed compared with 99 expected cases), for pancreatic cancer 0.50 (95% CI 0.28–0.81; 15 observed compared with 30 expected cases), and for lung cancer 0.68 (95% CI 0.49–0.91; 43 observed compared with 63 expected cases). The standardized incidence ratio for breast cancer among all levonorgestrel-releasing intrauterine system users was 1.19 (95% CI 1.13–1.25; 1,542 observed compared with 1,292 expected cases).

CONCLUSION: The levonorgestrel-releasing intrauterine system may have a protective effect against endometrial malignant transformation. Using the levonorgestrel-releasing intrauterine system for treatment of menorrhagia during reproductive years was associated with a lower incidence of endometrial, ovarian, pancreatic, and lung cancers than expected. Levonorgestrel-releasing intrauterine system use was associated with a higher than expected incidence of breast cancer.

LEVEL OF EVIDENCE: II

Using a levonorgestrel-releasing intrauterine system for treatment of menorrhagia is associated with reduced risk for endometrial cancer but is also associated with an elevated risk for breast cancer.

Department of Obstetrics and Gynecology, Hyvinkää Hospital, Hyvinkää, the Department of Obstetrics and Gynecology, Turku University Hospital, and the University of Turku, Turku, the Schools of Medicine and Health Sciences, University of Tampere, and the Department of Obstetrics and Gynecology, Tampere University Hospital, Tampere, and the Department of Obstetrics and Gynecology, Helsinki University Hospital, the University of Helsinki, and the Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland.

Corresponding author: Tuuli Soini, MD, Department of Obstetrics and Gynecology, Hyvinkää Hospital, Sairaalankatu 1, FI-05850 Hyvinkää, Finland; e-mail: tuuli.soini@hus.fi.

Supported by research grants from Helsinki University Hospital and Hyvinkää Hospital.

The authors thank Docent Ritva Prättälä, National Institute for Health and Welfare, for her help in identifying the levonorgestrel-releasing intrauterine system users in the national health survey data and Miia Artama, PhD, from the University of Helsinki for her assistance with statistical analyses.

Financial Disclosure The authors did not report any potential conflicts of interest.

© 2014 by The American College of Obstetricians and Gynecologists.