Hormonally mediated disturbance of angiogenesis in the human endometrium after exposure to intrauterine levonorgestrel.
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, alpha-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.


CONCLUSIONS
These findings suggest that the LNG has a localized effect on some vessels within the superficial endometrium.
McGavigan
C Jay
CJ
Department of Obstetrics and Gynaecology, University of Glasgow, Glasgow Royal Infirmary, Glasgow, UK.
Dockery
Peter
P
Metaxa-Mariatou
Vasiliki
V
Campbell
Dianne
D
Stewart
Colin J R
CJ
Cameron
Iain T
IT
Campbell
Steven
S
D000199:Actins / Q000378:metabolism; D000328:Adult; D001160:Arterioles / Q000473:pathology; D001808:Blood Vessels / Q000473:pathology; D004717:Endometrium / Q000098:blood supply* / Q000378:metabolism; D005260:Female; D006728:Hormones / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007434:Intrauterine Devices; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000009:adverse effects*; D009130:Muscle, Smooth / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism
D000199:Actins; D006728:Hormones; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D016912:Levonorgestrel; D009218:Myosins