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Hum. Reprod. Advance Access originally published online on March 10, 2005
Human Reproduction 2005 20(5):1410-1417; doi:10.1093/humrep/deh810
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions{at}oupjournals.org

Expression of vascular endothelial growth factors and their receptors in human endometrium from women experiencing abnormal bleeding patterns after prolonged use of a levonorgestrel-releasing intrauterine system

Björn Möller, Maria Rönnerdag, Guimin Wang, Viveca Odlind and Matts Olovsson1

Department of Women's and Children's Health, Uppsala University, SE-751 85 Uppsala, Sweden

1 To whom correspondence should be addressed. Email: matts.olovsson{at}kbh.uu.se

BACKGROUND: Menstrual bleeding disturbances are a common initial complaint among users of the levonorgestrel-releasing intrauterine system (LNG-IUS). In this study, women who experienced bleeding disturbances recurring after a previous period of problem-free use and who therefore wanted removal of their LNG-IUD were investigated. Vascular endothelial growth factors (VEGFs) and their receptors are thought to be involved in normal endometrial angiogenesis. The aim of the study was to elucidate the possible association of these VEGF and receptors with bleeding disturbances among users of LNG-IUS. METHODS: Endometrial biopsies were obtained from users of the LNG-IUS who complained of bleeding disturbances (n=17) and from women without such problems (n=14). The endometrial expression of these VEGFs and their receptors was analysed using immunohistochemistry. RESULTS: Endometrial endothelial cells from LNG-IUS users with menstrual bleeding disturbances exhibited significantly higher immunoreactivity for VEGFR-1 and VEGFR-3 than those from women without bleeding disturbances. Stromal cells showed significantly lower immunoreactivity for VEGF-A in samples from LNG-IUS users with bleeding disturbances than in those without. CONCLUSION: Changes in the expression of these angiogenic growth factors and their receptors in LNG-IUS-exposed endometrium might be involved in the formation of fragile and dysfunctional blood vessels that subsequently give rise to bleeding disturbances.

Key words: angiogenesis/endometrium/levonorgestrel-releasing intrauterine system/menstrual bleeding disturbances/vascular endothelial growth factors


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