title: Evaluation of a new, low-dose levonorgestrel intrauterine contraceptive system over 5 years of use.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Gemzell-Danielsson
authors.affiliation: VL-Medi Clinical Research Center, Helsinki, Finland.
authors.forename: Dan
authors.initials: D
authors.lastname: Apter
authors.affiliation: Gynaecological Centre Dermout & Albicher, Alkmaar, The Netherlands.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Dermout
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Faustmann
authors.affiliation: Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Rosen
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmelter
authors.affiliation: Bayer Pharma AG, Berlin, Germany. Electronic address: martin.merz@bayer.com.
authors.forename: Martin
authors.initials: M
authors.lastname: Merz
authors.affiliation: Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, CA, USA.
authors.forename: Anita
authors.initials: A
authors.lastname: Nelson
mesh_terms: D000293:Adolescent; D000328:Adult; D003271:Contraceptive Agents, Female / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007436:Intrauterine Devices, Medicated / Q000009:adverse effects* / Q000706:statistics & numerical data; D016912:Levonorgestrel / Q000008:administration & dosage*; D010298:Parity; D055815:Young Adult
chemical_list: D003271:Contraceptive Agents, Female; D016912:Levonorgestrel
keywords: Contraception; Intrauterine system; LARC; LNG-IUS; Levonorgestrel