The effect of a levonorgestrel-releasing intrauterine system on angiogenic growth factors in the endometrium.

Background: The study aim was to investigate the effects of a levonorgestrel-releasing intrauterine system (LNG-IUS) on the secretion profiles and level of mRNA transcripts for angiogenic growth factors including vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-beta1, basic fibroblast growth factor (bFGF) and endothelial growth factor (EGF) in the endometrium, and their levels in plasma.

Methods: Blood and endometrial samples were collected from 15 women using LNG-IUS at pre-insertion and at 1, 3, 6 and 12 months following the use of contraception. Using enzyme-linked immunosorbent assay (ELISA) and semi-quantitative reverse transcription techniques, angiogenic growth factors were measured in the plasma and endometrial tissue extracts.

Results: A significant increase in endometrial tissue levels of VEGF at 3 and 6 months (P < 0.007, P < 0.01), TGF-beta1 at 6 and 12 months (P < 0.002, P < 0.007) and bFGF at 1 and 6 months (P < 0.004, P < 0.008) respectively were observed following insertion of LNG-IUS. A corresponding increase in mRNA expression of TGF-beta1 and bFGF were also observed. The LNG-IUS had no effect on endometrial EGF levels. No significant differences were noted in plasma levels of bFGF, EGF and TGF-beta1, while VEGF was not detectable in all plasma samples assayed. A positive correlation was observed between endometrial tissue VEGF and bleeding/spotting days in the reference period (r = 0.705, P < 0.015).

Conclusion: These results provide the first evidence that more than one angiogenic factor could be implicated in aberrant endometrial angiogenesis resulting in breakthrough bleeding in LNG-IUS acceptors.