Influence of the levonorgestrel-releasing intrauterine system on the risk of breast cancer: a systematic review

Arch Gynecol Obstet. 2023 Jun;307(6):1747-1761. doi: 10.1007/s00404-022-06640-y. Epub 2022 Jun 18.

Abstract

Purpose: The intention of this systematic review was to analyze the literature on breast cancer (BC) and the use of the levonorgestrel-releasing intrauterine system (LNG-IUS).

Methods: The literature was searched in Medline, Embase, Cochrane Library, CINAHL, Web of Science and ClinicalTrials.com and included search terms related to breast cancer and LNG-IUS. After elimination of duplicates, 326 studies could be identified and were assessed according to inclusion and exclusion criteria. In the end, 10 studies met the defined criteria and were included in the systematic review.

Results: 6 out of the 10 selected studies were cohort studies, three were case-control studies and one a systematic review/meta-analysis. 6 found a positive association between BC and the use of LNG-IUS. One study only found an increased risk for invasive BC in the subgroup of women aged 40-45 years. In contrast, three studies showed no indication of a higher BC risk.

Conclusion: The results imply an increased BC risk in LNG-IUS users, especially in postmenopausal women and with longer duration of use. Positive effects of the LNG-IUS such as reduced risks for other hormonal cancers have been observed, were, however, not focus of this systematic review. The heterogeneity of the analyzed studies and vast number of confounding factors call for further investigations in this issue. Patients should be advised according to their individual risk profile and hormone-free alternatives may be considered for women with a history of BC.

Keywords: Breast cancer; Contraception; Hormone replacement therapy; Levonorgestrel; Levonorgestrel-releasing intrauterine system; Postmenopause; Premenopause.

Publication types

  • Systematic Review
  • Meta-Analysis
  • Review

MeSH terms

  • Breast Neoplasms* / chemically induced
  • Breast Neoplasms* / epidemiology
  • Contraceptive Agents, Female* / adverse effects
  • Female
  • Humans
  • Intrauterine Devices, Medicated* / adverse effects
  • Levonorgestrel / adverse effects
  • Time Factors

Substances

  • Levonorgestrel
  • Contraceptive Agents, Female