title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Women's and Children's Health, Uppsala University, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Möller
authors.forename: Maria
authors.initials: M
authors.lastname: Rönnerdag
authors.forename: Guimin
authors.initials: G
authors.lastname: Wang
authors.forename: Viveca
authors.initials: V
authors.lastname: Odlind
authors.forename: Matts
authors.initials: M
authors.lastname: Olovsson
mesh_terms: D000328:Adult; D001808:Blood Vessels / Q000187:drug effects; D003271:Contraceptive Agents, Female / Q000009:adverse effects*; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D007436:Intrauterine Devices, Medicated / Q000009:adverse effects*; D016912:Levonorgestrel / Q000009:adverse effects*; D008599:Menstruation Disturbances / Q000139:chemically induced* / Q000378:metabolism; D011374:Progesterone / Q000097:blood; D040262:Receptors, Vascular Endothelial Growth Factor / Q000187:drug effects / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors / Q000187:drug effects / Q000378:metabolism*
chemical_list: D003271:Contraceptive Agents, Female; D042442:Vascular Endothelial Growth Factors; D011374:Progesterone; D004958:Estradiol; D016912:Levonorgestrel; D040262:Receptors, Vascular Endothelial Growth Factor