Effects of levonorgestrel-releasing intra-uterine system on the expression of vascular endothelial growth factor and adrenomedullin in the endometrium in adenomyosis
Laoag-Fernandez,Jovelle B.; Maruo,Takeshi; Pakarinen,Paivi; Spitz,Irving M.; Johansson,Elof D.B.
Human Reproduction 18(4): 694-699
Publication date: 2003
The levonorgestrel-releasing intra-uterine system(LNg-IUS) has been used to control menorrhagia, but irregularbleeding during the first 3 months of use was the most notableside effect. Endometrial angiogenesis is believed to be regulatedby angiogenic factors. The study aim was to evaluate the effectsof LNg-IUS on vascular endothelial growth factor (VEGF) andadrenomedullin (AM) expression in the endometrium.
VEGF and AM expression were analysed using the avidin-biotinimmunoperoxidase method on endometrial curettage specimens frommenorrhagic women associated with adenomyosis before and 3 monthsafter LNg-IUS insertion.
VEGF expression was abundantboth in the endometrial glands and stroma before LNg-IUS insertion,but became scanty 3 months after insertion. No immunostainingfor AM was noted in the endometrial glands and stroma beforeLNg-IUS insertion, whereas AM immunostaining became prominentin the endometrial glands and stroma 3 months after LNg-IUSuse.
This is the first study to demonstrate thatLNg-IUS insertion results in decreased expression of VEGF andincreased expression of AM in the endometrial glands and stromaafter 3 months of use. The results obtained suggest that theincrease in AM expression in the endometrium may be responsiblefor the frequent occurrence of irregular bleeding during theinitial 3 months of LNg-IUS use.