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 Mar;97(3):616-22.e1-3. doi: 10.1016/j.fertnstert.2011.12.003. Epub 2012 Jan 4.


Objective: To identify an appropriate dose for a new contraceptive levonorgestrel intrauterine system (LNG-IUS).

Design: Randomized, open-label, three-arm, phase II study.

Setting: Thirty-seven centers in five European countries.

Patient(s): Parous or nulliparous women aged 21-40 years.

Intervention(s): Treatment with LNG-IUSs with initial in vitro release rates of 12 or 16 μg/d (LNG-IUS12/16) or 20 μg/d (Mirena).

Main outcome measure(s): Pearl index, bleeding profile, ease/pain of placement/removal, adverse events.

Result(s): A total of 738 subjects had an LNG-IUS placed (LNG-IUS12, n = 239; LNG-IUS16, n = 245; Mirena, n = 254). One, 5, and 0 pregnancies occurred in the LNG-IUS12, LNG-IUS16, and Mirena groups, respectively (3-year unadjusted Pearl indices: 0.17, 0.82, and 0). The bleeding profiles were similar in all groups, although total bleeding and spotting days decreased with increasing LNG dose. During 3 years, 10 subjects in the LNG-IUS12 (2 women), LNG-IUS16 (3 women), and Mirena (5 women) groups reported serious adverse events, possibly related to study treatment. Placement of LNG-IUS12 and LNG-IUS16 was considered easy in 94% versus 86.2% in the Mirena group and 72.3% in the LNG-IUS12/LNG-IUS16 group reported either "no pain" or only "mild pain" during placement versus 57.9% in the Mirena group.

Conclusion(s): LNG-IUS12 and LNG-IUS16 provided effective contraception, acceptable bleeding patterns, and were well tolerated compared with Mirena.

Trial registration: ClinicalTrials.gov NCT00185380.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Contraceptives, Oral, Synthetic / administration & dosage*
  • Contraceptives, Oral, Synthetic / adverse effects
  • Dose-Response Relationship, Drug
  • Europe
  • Female
  • Humans
  • Intrauterine Devices, Medicated* / adverse effects
  • Levonorgestrel / administration & dosage*
  • Levonorgestrel / adverse effects
  • Menstruation / drug effects*
  • Pregnancy
  • Pregnancy, Unplanned
  • Time Factors
  • Treatment Outcome
  • Young Adult


  • Contraceptives, Oral, Synthetic
  • Levonorgestrel

Associated data

  • ClinicalTrials.gov/NCT00185380