Persistence of an intact endometrial matrix and vessels structure in women exposed to VA-2914, a selective progesterone receptor modulator.
BACKGROUND
VA-2914 is a selective progesterone receptor modulator with potential contraceptive activity that induces amenorrhea, whereas progestins cause endometrial spotting and bleeding. This abnormal bleeding due to progestins is a consequence of focal stromal proteolysis by an increase in naked vessel size and density.


OBJECTIVE
Our objective was to quantify the effects of VA-2914 on endometrial vascularization, fibrillar matrix, and vascular endothelial growth factor (VEGF)-A expression in endometrial biopsies from 41 women before and after 12 wk daily treatment with a placebo, or 2.5, 5, or 10 mg VA-2914.


METHODS
Collagen fibrillar network was stained by silver impregnation. Vessel area, density, and structure were quantified with a computer-assisted image analysis system after double immunostaining using an anti-von Willebrand factor (endothelial cells) and an anti-alpha smooth muscle actin (vascular smooth muscle cells) marker antibody. VEGF-A mRNAs were quantified by RT-PCR and localized by immunohistochemistry.


RESULTS
The endometrial vessels, collagen network, and mRNA levels of VEGF-A were identical during the luteal phase at baseline and in VA-2914 treated women. VEGF-A distribution was unchanged.


CONCLUSIONS
VA-2914 does not alter the endometrial matrix and cells, and does not modify the endometrial vessel morphology as compared with baseline biopsies.
Ravet
S
S
Department of Gynecology, Centre Hospitalier Universitaire, University of Liege, Liege, Belgium.
Munaut
C
C
Blacher
S
S
Brichant
G
G
Labied
S
S
Beliard
A
A
Chabbert-Buffet
N
N
Bouchard
P
P
Foidart
J-M
JM
Pintiaux
A
A
D000199:Actins / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D001706:Biopsy; D004717:Endometrium / Q000098:blood supply* / Q000166:cytology / Q000187:drug effects*; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009649:Norpregnadienes / Q000494:pharmacology*; D010919:Placebos; D011374:Progesterone / Q000378:metabolism; D011980:Receptors, Progesterone / Q000187:drug effects / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D055815:Young Adult; D014841:von Willebrand Factor / Q000378:metabolism
D000199:Actins; D009649:Norpregnadienes; D010919:Placebos; D011980:Receptors, Progesterone; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor; D011374:Progesterone; D004958:Estradiol; C094854:ulipristal