Human Reproduction, Vol. 18, No. 1, 77-84,
January 2003
© 2003 European Society of Human Reproduction and Embryology
Hormonally mediated disturbance of angiogenesis in the human endometrium after exposure to intrauterine levonorgestrel
1 Department of Obstetrics and Gynaecology, University of Glasgow, Glasgow Royal Infirmary, Glasgow, UK, 2 Department of Anatomy, University College, Cork, Ireland, 3 Department of Pathology, Glasgow Royal Infirmary, Castle Street, Glasgow and 4 Maternal, Fetal and Neonatal Physiology Group, Fetal Origins of Adult Disease Division, University of Southampton, Princess Anne Hospital, Coxford Road, Southampton, UK 5 To whom correspondence should be addressed at Department of Obstetrics and Gynaecology, University of Glasgow, Glasgow Royal Infirmary, 10 Alexandra Parade, Glasgow G31 2ER, UK. e-mail: gqta05{at}udcf.gla.ac.uk
BACKGROUND: The levonorgestrel intrauterine system (LNG-IUS) is a contraceptive device that is used for treatment of menorrhagia. The system induces inter-menstrual bleeding within the first few months after insertion. We hypothesized that this bleeding might be associated with a change in vascular development. METHODS: A randomized, controlled study was undertaken on 48 women. RESULTS: Hysterectomy specimens were obtained and immunocytochemistry was carried out with antibodies to CD31, 
-smooth muscle actin and myosin. Stereological measurement of blood vessels was also undertaken. Most vessels appeared normal, including the arterioles. Large thin-walled vessels were present in the superficial endometrium of the treated group but were almost completely absent in the controls. The distribution of cytoskeletal markers revealed well-formed basal arterioles with more widespread expression in the superficial stroma than was found in untreated tissue. The volume fraction of blood vessels (P = 0.0001), the number of vessel cross-sections per unit area (P = 0.0003) and the cross-sectional diameters of the largest vascular lumens (P = 0.0001) were significantly increased following treatment with LNG-IUS. However, there was no difference in the median values of vessel diameter or the vascular surface density. CONCLUSION: These findings suggest that the LNG has a localized effect on some vessels within the superficial endometrium.
Key words: breakthrough bleeding/endometrium/levonorgestrel intrauterine system/progestogen/vasculature
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