Endothelial function in women using levonorgestrel-releasing intrauterine system (LNG-IUS)

Contraception. 2013 Apr;87(4):396-403. doi: 10.1016/j.contraception.2012.12.008. Epub 2012 Dec 20.


Background: Oral levonorgestrel has been linked to increased cardiovascular risk, but currently, no information is available on the effect of the levonorgestrel-releasing intrauterine system (LNG-IUS) on endothelial dysfunction. The objective of this study was to assess endothelial function in LNG-IUS users.

Study design: Sixty women underwent insertion of either an LNG-IUS (n=30) as study group or Copper-T intrauterine contraceptive device (TCu 380A intrauterine device) as control group (n=30). In the midluteal phase of menstrual cycle, endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent dilatation of brachial artery were studied before and after 3, 6 and 12 months of device insertion. We also assessed the correlation of FMD and serum concentrations of estradiol (E2), progesterone (P) and LNG.

Results: With LNG-IUS, there was a nonsignificant decrease in mean FMD of brachial artery (p>.05) compared with the control group at different time points of the study. Before LNG-IUS, reactive hyperemia caused an 8.3%±1.3% increase in brachial artery diameter compared with 7.1%±1.1%, 7.4%±0.9% and 7.5%±0.9% after 3, 6 and 12 months of LNG-IUS (p>.05). The mean±SD LNG plasma levels at 3, 6 and 12 months of LNG-IUS application were 228±87, 204±94 and 191±79 pg/mL, respectively. E2 levels were comparable in women of both studied groups. Mean P levels were significantly lower after LNG-IUS insertion compared with before device insertion and with the control group (p<.05) at all study visits. No correlation was found between LNG levels and FMD.

Conclusions: A nonsignificant change detected in endothelial function in LNG-IUS indicates that it has no increased cardiovascular risk.

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Contraceptive Agents, Female / administration & dosage
  • Contraceptive Agents, Female / adverse effects*
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiology*
  • Female
  • Humans
  • Intrauterine Devices, Medicated / adverse effects*
  • Levonorgestrel / administration & dosage
  • Levonorgestrel / adverse effects*
  • Pregnancy
  • Prospective Studies
  • Young Adult


  • Contraceptive Agents, Female
  • Levonorgestrel