Hormonally mediated disturbance of angiogenesis in the human endometrium after exposure to intrauterine levonorgestrel

Abstract

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, α-smooth muscle actin and myosin. Stereological measurement of blood vessel 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.