Effect of mifepristone on endometrial matrix metalloproteinase expression and leukocyte abundance in new medroxyprogesterone acetate users.
OBJECTIVE
This double-blind, placebo-controlled study was conducted to evaluate the molecular mechanism of mifepristone controlling breakthrough bleeding (BTB) in new depot-medroxyprogesterone acetate (DMPA) users.


METHODS
A total of 50 regularly cycling women who were new starters of DMPA were randomized to receive 50 mg of mifepristone or placebo once every 14 days for six cycles. Endometrial biopsies were obtained on each patient before, during and after treatment. Endometrial matrix metalloproteinase 1 (MMP-1) and MMP-9 protein and mRNA were determined by immunohistochemistry and real-time PCR, respectively. The number of T lymphocytes (CD3-positive) and mast cells (mast tryptase-positive) was evaluated by immunohistochemistry.


RESULTS
MMP-1, MMP-9, CD3-positive and mast tryptase-positive cells increased following the DMPA treatment. Addition of mifepristone to DMPA-exposed endometrium for 1 week significantly decreased stromal MMP-9 expression and numbers of CD3-positive and mast tryptase-positive cells.


CONCLUSIONS
The decreased rates of BTB in new users of DMPA by mifepristone are associated with decreased MMP-1 and MMP-9 expression and fewer mast and T cells.
Li
Aimin
A
Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. aiminli@usc.edu
Felix
Juan C
JC
Yang
Wangrong
W
Xiong
David W
DW
Minoo
Parviz
P
Jain
John K
JK
D000293:Adolescent; D000328:Adult; D003271:Contraceptive Agents, Female; D003280:Contraceptives, Oral, Synthetic / Q000008:administration & dosage / Q000627:therapeutic use*; D017931:DNA Primers; D004311:Double-Blind Method; D004717:Endometrium / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007962:Leukocytes / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D017258:Medroxyprogesterone Acetate; D008875:Middle Aged; D015735:Mifepristone / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome; D014592:Uterine Hemorrhage / Q000378:metabolism / Q000517:prevention & control*
D003271:Contraceptive Agents, Female; D003280:Contraceptives, Oral, Synthetic; D017931:DNA Primers; D012333:RNA, Messenger; D015735:Mifepristone; D017258:Medroxyprogesterone Acetate; D020782:Matrix Metalloproteinases