title: Effects of levonorgestrel-releasing intra-uterine system on the expression of vascular endothelial growth factor and adrenomedullin in the endometrium in adenomyosis.
abstract: BACKGROUND
  The levonorgestrel-releasing intra-uterine system (LNg-IUS) has been used to control menorrhagia, but irregular bleeding during the first 3 months of use was the most notable side effect. Endometrial angiogenesis is believed to be regulated by angiogenic factors. The study aim was to evaluate the effects of LNg-IUS on vascular endothelial growth factor (VEGF) and adrenomedullin (AM) expression in the endometrium.
  
  
  METHODS
  VEGF and AM expression were analysed using the avidin-biotin immunoperoxidase method on endometrial curettage specimens from menorrhagic women associated with adenomyosis before and 3 months after LNg-IUS insertion.
  
  
  RESULTS
  VEGF expression was abundant both in the endometrial glands and stroma before LNg-IUS insertion, but became scanty 3 months after insertion. No immunostaining for AM was noted in the endometrial glands and stroma before LNg-IUS insertion, whereas AM immunostaining became prominent in the endometrial glands and stroma 3 months after LNg-IUS use.
  
  
  CONCLUSIONS
  This is the first study to demonstrate that LNg-IUS insertion results in decreased expression of VEGF and increased expression of AM in the endometrial glands and stroma after 3 months of use. The results obtained suggest that the increase in AM expression in the endometrium may be responsible for the frequent occurrence of irregular bleeding during the initial 3 months of LNg-IUS use.
authors.affiliation: Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: J B
authors.initials: JB
authors.lastname: Laoag-Fernandez
authors.forename: T
authors.initials: T
authors.lastname: Maruo
authors.forename: P
authors.initials: P
authors.lastname: Pakarinen
authors.forename: I M
authors.initials: IM
authors.lastname: Spitz
authors.forename: E
authors.initials: E
authors.lastname: Johansson
mesh_terms: D053607:Adrenomedullin; D000328:Adult; D003271:Contraceptive Agents, Female / Q000008:administration & dosage*; D004715:Endometriosis / Q000150:complications / Q000378:metabolism*; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D007436:Intrauterine Devices, Medicated; D016912:Levonorgestrel / Q000008:administration & dosage*; D008595:Menorrhagia / Q000188:drug therapy / Q000209:etiology; D010455:Peptides / Q000378:metabolism*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D003271:Contraceptive Agents, Female; D010455:Peptides; D042461:Vascular Endothelial Growth Factor A; D053607:Adrenomedullin; D016912:Levonorgestrel