Full length article| Volume 210, P22-28, March 2017

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Evaluation of a new, low-dose levonorgestrel intrauterine contraceptive system over 5 years of use

Published:November 20, 2016DOI:



      To evaluate the efficacy and safety of a new, low-dose levonorgestrel intrauterine contraceptive system (LNG-IUS 12) for up to 5 years of use.

      Study design

      In this Phase III study, 2885 nulliparous and parous women aged 18–35 years were randomized to LNG‐IUS 8 or LNG-IUS 12 for 3 years. After 3 years, women using LNG-IUS 12 could continue for up to 2 additional years (5 years total). The primary outcome was occurrence of pregnancy (Pearl Index). Secondary outcomes included safety, bleeding, dysmenorrhea, discontinuations, and user satisfaction.


      From August 2007 through May 2008, out of 2885 women who were enrolled, 1453 were randomized to LNG-IUS 12. Placement was attempted in 1452/1453 (full analysis set). Mean age at baseline was 27.1 years; 39.5% were nulliparous. The cumulative 5-year Pearl Index (PI) was 0.29; the 5-year cumulative failure rate was 1.4%. The 5-year PI for ectopic pregnancy was 0.18. Over 5 years, 55.3% of women reported study drug-related treatment-emergent adverse events (TEAEs). Crude incidences of pelvic inflammatory disease, uterine perforation, and complete/partial LNG-IUS 12 expulsion were 0.6%, 0.2%, and 3.7%, respectively. Women using LNG-IUS 12 generally experienced less frequent bleeding over time. The incidence of amenorrhea during the last 90-day reference interval (end of Year 5) was 22.6%. Overall, 870 (59.9%) and 550 (37.9%) women completed 3 and 5 years of treatment, respectively; 77.8% of women who entered the extension phase completed 5 years of use. Over 5 years, 22.6% discontinued due to TEAEs, including 13 women who discontinued due to pregnancy; 76 discontinued due to bleeding problems including amenorrhea; and 163 discontinued due to desire for pregnancy, 71.2% of whom conceived within 12 months.


      In this study including parous and nulliparous women, LNG-IUS 12 was highly effective over 5 years of use and associated with a favorable safety profile. LNG‐IUS 12 offers women a low-dose contraceptive option for up to 5 years.


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      1. American College of Obstetricians and Gynecologists ACOG Practice Bulletin No. 121: Long-acting reversible contraception: implants and intrauterine devices.
        Obstet Gynecol. 2011; 118: 184-196
      2. National Institute for Health and Clinical Excellence Long-acting reversible contraception: the effective and appropriate use of long-acting reversible contraception. 2013. Available from: [Last accessed 26 January 2016].

      3. World Health Organization Medical eligibility criteria for contraceptive use: fifth edition. 2015. Available from: [Last accessed 4 February 2016].

      4. Committee on Adolescence Contraception for adolescents.
        Pediatrics. 2014; 134: e1244-e1256
      5. Bayer HealthCare Pharmaceuticals Inc Jaydess® Summary of Product Characteristics. 2015. Available from: [Last accessed 4 February 2016].

      6. Actavis Liletta® Prescribing Information. 2015. Available from: [Last accessed 19 November 2015].

      7. Bayer HealthCare Pharmaceuticals Inc. Mirena® (levonorgestrel-releasing intrauterine system) Prescribing Information. 2015. Available from: [Last accessed 16 February 2016].

        • Nelson A.L.
        • Apter D.
        • Hauck B.
        • et al.
        Two low-dose levonorgestrel intrauterine contraceptive systems: a randomized controlled trial.
        Obstet Gynecol. 2013; 122: 1205-1213
      8. Faculty of Sexual & Reproductive Healthcare New Product Review from the Clinical Effectiveness Unit Jaydess® Levonorgestrel Intrauterine System (LNG-IUS). 2014. Available from: [Last accessed 1 December 2016].

      9. Faculty of Sexual & Reproductive Healthcare New Product Review from the Clinical Effectiveness Unit: Levosert. 2015. Available from: [Last accessed 1 December 2016].

      10. European Medicines Agency, Guideline on Clinical Investigation of Steroid Contraceptives in Women. 2005. Available from: [Last accessed 12 February 2016].

        • Benda N.
        • Gerlinger C.
        • van der Meulen E.A.
        • Endrikat J.
        Sample size calculation for clinical studies on the efficacy of a new contraceptive method.
        Biom J. 2004; 46: 141-150
        • Gerlinger C.
        • Endrikat J.
        • van der Meulen E.A.
        • Dieben T.O.
        • Düsterberg B.
        Recommendation for confidence interval and sample size calculation for the Pearl Index.
        Eur J Contracept Reprod Health Care. 2003; 8: 87-92
        • Eisenberg D.
        • Schreiber C.
        • Turok D.K.
        • et al.
        Three-year efficacy and safety of a new 52-mg levonorgestrel-releasing intrauterine system.
        Contraception. 2015; 92: 10-16
      11. Bayer HealthCare. Data on File. 2015.

        • Gemzell-Danielsson K.
        • Schellschmidt I.
        • Apter D.
        A randomized, phase II study describing the efficacy, bleeding profile, and safety of two low-dose levonorgestrel-releasing intrauterine contraceptive systems and Mirena.
        Fertil Steril. 2012; 97: 616-622
        • Andersson K.
        • Odlind V.
        • Rybo G.
        Levonorgestrel-releasing and copper-releasing (Nova T) IUDs during five years of use: a randomized comparative trial.
        Contraception. 1994; 49: 56-72
        • Malhotra R.
        • Ostbye T.
        • Riley C.M.
        • Finkelstein E.A.
        Young adult weight trajectories through midlife by body mass category.
        Obesity (Silver Spring). 2013; 21: 1923-1934
        • Andersson K.
        • Batar I.
        • Rybo G.
        Return to fertility after removal of a levonorgestrel-releasing intrauterine device and Nova-T.
        Contraception. 1992; 46: 575-584
        • Sivin I.
        • Stern J.
        • Diaz S.
        • et al.
        Rates and outcomes of planned pregnancy after use of Norplant capsules, Norplant II rods, or levonorgestrel-releasing or copper TCu 380Ag intrauterine contraceptive devices.
        Am J Obstet Gynecol. 1992; 166: 1208-1213
        • Mansour D.
        • Gemzell-Danielsson K.
        • Inki P.
        • Jensen J.T.
        Fertility after discontinuation of contraception: a comprehensive review of the literature.
        Contraception. 2011; 84: 465-477

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