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Human Reproduction, Vol. 18, No. 4, 694-699, April 2003
© 2003 European Society of Human Reproduction and Embryology

Effects of levonorgestrel-releasing intra-uterine system on the expression of vascular endothelial growth factor and adrenomedullin in the endometrium in adenomyosis

J.B. Laoag-Fernandez1, T. Maruo1,5, P. Pakarinen2, I.M. Spitz3 and E. Johansson4

1 Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan, 2 Department of Obstetrics and Gynecology, University of Helsinki, Finland, 3 Institute of Hormone Research, Shaare Zedek Medical Center, Jerusalem, Israel and 4 Population Council, New York, USA

5 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. e-mail: maruo{at}kobe-u.ac.jp

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.

Key words: adrenomedullin/endometrium/levonorgestrel-releasing intra-uterine system/vascular endothelial growth factor


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