title: Quantitative levonorgestrel plasma level measurements in patients with regular and prolonged use of the levonorgestrel-releasing intrauterine system.
abstract: BACKGROUND
  The levonorgestrel-releasing intrauterine system (LNG-IUS) is well accepted as an easy-to-use contraceptive with an excellent side-effect profile. It contains a reservoir of 52 mg of levonorgestrel (LNG) with continuous release of the steroid. Its contraceptive use is approved for 5 years. The aim of this study was to determine the plasma concentration of LNG and its variation with time in patients with in-dwelling LNG-IUS Mirena®.
  
  
  METHODS
  In this study, we determined LNG plasma concentrations in 110 women with LNG-IUS at different time points of use. Time from insertion of the system in the study population ranged from 20 days to 11.1 years. Quantitative LNG levels were determined using a validated liquid chromatography-tandem mass spectrometry assay.
  
  
  RESULTS
  The mean±SD LNG plasma level in all women was 147±59 pg/mL. A highly significant negative correlation between LNG plasma level and LNG-IUS time of use could be demonstrated. In the first year of use, LNG plasma level was as high as 191±71 pg/mL, decreasing to 157±68 pg/mL in the second year and 134±41 pg/mL in the third year. Even after exceeding the recommended period of LNG-IUS use, systemic LNG concentrations were detectable: 133±38 pg/mL in the sixth year, 133±48 pg/mL in the seventh year and 117±45 pg/mL in the eighth year. Furthermore, a significant negative correlation between LNG plasma level and body mass index could be shown.
  
  
  CONCLUSIONS
  Systemic LNG concentrations can be found in all patients with LNG-IUS IUS. However, concentrations are much lower than in other forms of LNG application. Moreover, this study demonstrates that a systemic effect of LNG-IUS can also be found after the recommended contraceptive lifespan of 5 years.
authors.affiliation: Department of Gynecological Endocrinology and Reproductive Medicine, Innsbruck Medical University, A-6020 Innsbruck, Austria.
authors.forename: Beata
authors.initials: B
authors.lastname: Seeber
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Ziehr
authors.forename: Andreas
authors.initials: A
authors.lastname: Gschlieβer
authors.forename: Aandrea
authors.initials: A
authors.lastname: Gschliesser
authors.forename: Christina
authors.initials: C
authors.lastname: Moser
authors.forename: Verena
authors.initials: V
authors.lastname: Mattle
authors.forename: Christoph
authors.initials: C
authors.lastname: Seger
authors.forename: Andrea
authors.initials: A
authors.lastname: Griesmacher
authors.forename: Nicole
authors.initials: N
authors.lastname: Concin
authors.forename: Hans
authors.initials: H
authors.lastname: Concin
authors.forename: Ludwig
authors.initials: L
authors.lastname: Wildt
mesh_terms: D000293:Adolescent; D000328:Adult; D001317:Austria; D015992:Body Mass Index; D003271:Contraceptive Agents, Female / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007436:Intrauterine Devices, Medicated / Q000009:adverse effects; D016912:Levonorgestrel / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000378:metabolism; D050177:Overweight / Q000097:blood / Q000378:metabolism; D017410:Practice Guidelines as Topic; D012189:Retrospective Studies; D013997:Time Factors; D055815:Young Adult
chemical_list: D003271:Contraceptive Agents, Female; D016912:Levonorgestrel