What is the best drug treatment for premenopausal women with bleeding irregularities using the levonorgestrel-releasing intrauterine system? A systematic review

P.A.H.H. van der Heijden*, R.M.G. Tibosch, P.M.A.J. Geomini, S. Veersema, L.M. Bullens, E.J.L.G. Delvaux, B.N. Bui, M.Y. Bongers

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review


Objective Up to 60% of women discontinue using the levonorgestrel-releasing intrauterine system (LNG-IUS) within 5 years because of bleeding irregularities, pain and/or systemic progestogenic adverse effects. The aim of the study was to assess treatment options for bleeding irregularities in women using the 52 mg LNG-IUS. Methods Database searches of Medline, Embase/Ovid and the Cochrane Library were carried out, and journals were searched by hand, for relevant studies published from database inception to March 2020. Inclusion criteria were randomised controlled trials (RCTs), prospective cohort studies and case-control studies of premenopausal women using the LNG-IUS and receiving medical treatment for bleeding irregularities. Screening, data extraction and quality assessment of retrieved articles were carried out independently by two pairs of reviewers. The primary outcome was the reduction of bleeding/spotting days. Results Of the 3061 studies identified, eight met our inclusion criteria: six RCTs and two prospective cohort studies. The eight studies enrolled a total of 677 women who were treated with tamoxifen, mifepristone, ulipristal acetate, naproxen, oestradiol, mefenamic acid, tranexamic acid or the progesterone receptor modulator CDB 2914. The results of our analysis indicated that naproxen may be effective for the prophylactic treatment of bleeding immediately (<12 weeks) after LNG-IUS insertion (high level of evidence). Oestradiol may be effective in treating ongoing bleeding irregularities >6 months after insertion (low level of evidence). Conclusion Evidence for the medical treatment of (ongoing) bleeding irregularities during use of the LNG-IUS is lacking and more research is needed on the topic.
Original languageEnglish
Pages (from-to)484-491
Number of pages8
JournalEuropean Journal of Contraception and Reproductive Health Care
Issue number6
Publication statusPublished - 1 Nov 2020


  • bleeding irregularities
  • discontinuation
  • lng-ius
  • mirena
  • treatment
  • Bleeding irregularities
  • Mirena

Cite this