Quantitative levonorgestrel plasma level measurements in patients with regular and prolonged use of the levonorgestrel-releasing intrauterine system

Contraception. 2012 Oct;86(4):345-9. doi: 10.1016/j.contraception.2012.01.015. Epub 2012 Mar 6.


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®.

Study design: 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.

Conclusion: 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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Austria
  • Body Mass Index
  • Contraceptive Agents, Female / administration & dosage
  • Contraceptive Agents, Female / adverse effects
  • Contraceptive Agents, Female / blood
  • Contraceptive Agents, Female / pharmacokinetics*
  • Female
  • Humans
  • Intrauterine Devices, Medicated* / adverse effects
  • Levonorgestrel / administration & dosage
  • Levonorgestrel / adverse effects
  • Levonorgestrel / blood
  • Levonorgestrel / pharmacokinetics*
  • Middle Aged
  • Obesity / blood
  • Obesity / metabolism
  • Overweight / blood
  • Overweight / metabolism
  • Practice Guidelines as Topic
  • Retrospective Studies
  • Time Factors
  • Young Adult


  • Contraceptive Agents, Female
  • Levonorgestrel