Endometrial vessel maturation in women exposed to levonorgestrel-releasing intrauterine system for a short or prolonged period of time.
BACKGROUND
Levonorgestrel-releasing intrauterine system (LNG-IUS), although inserted to reduce heavy menstruation, causes irregular early transient bleeding. The objective of the study was to document quantitative changes in endometrial vessels of short- (< or =3 months) and long-term (> or =12 months) LNG users. The area, density and maturation of endometrial vessels were quantified in 19 endometrial biopsies of women with LNG-IUS and in 10 normally ovulating patients during mid-luteal phase.


METHODS
Vessel maturation was evaluated by double immunostaining using anti-von Willebrand factor (endothelial cell marker) and anti-alpha Smooth Muscle Actin (vascular smooth muscle cells) antibodies. Vessel area, number and density were quantified with a novel computer-assisted image analysis system.


RESULTS
Endometrium exposed to LNG-IUS for 1-3 months displayed a 11.5-fold increase in small naked vessel number. The partially mature vessel (alphaSMA partially positive) number increased six times. After long-term LNG-IUS treatment, the immature and partially mature vessel number remained four times higher than in the control group. Vessel area and density also increased dramatically in a time-dependent pattern with LNG-IUS use.


CONCLUSIONS
Levonorgestrel affects blood vessel number, area, density and maturation in a time-dependent pattern that may explain the early transient increase in breakthrough bleeding with the LNG-IUS.
Stéphanie
Ravet
R
Laboratory of Tumor and Development Biology, Center of Experimental Cancer Research, University de Liège, Tour de Pathologie (B23), Avenue de l'hôpital, GIGA-R, Sart-Tilman, B-4000 Liège, Belgium.
Labied
Soraya
S
Blacher
Silvia
S
Frankenne
Francis
F
Munaut
Carine
C
Fridman
Viviana
V
Beliard
Aude
A
Foidart
Jean-Michel
JM
Nisolle
Michelle
M
D000199:Actins / Q000378:metabolism; D000328:Adult; D001706:Biopsy; D003271:Contraceptive Agents, Female / Q000009:adverse effects*; D004717:Endometrium / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006801:Humans; D016912:Levonorgestrel / Q000009:adverse effects*; D008599:Menstruation Disturbances / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D011446:Prospective Studies; D017154:Stromal Cells / Q000187:drug effects / Q000473:pathology; D013997:Time Factors; D014841:von Willebrand Factor / Q000378:metabolism
D000199:Actins; D003271:Contraceptive Agents, Female; D014841:von Willebrand Factor; D016912:Levonorgestrel