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Original research article| Volume 76, ISSUE 1, P57-65, July 2007

Effect of mifepristone on endometrial matrix metalloproteinase expression and leukocyte abundance in new medroxyprogesterone acetate users

  • Aimin Li
    Correspondence
    Corresponding author. Tel.: +1 323 226 3008; fax: +1 323 226 2850.
    Affiliations
    Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
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  • Juan C. Felix
    Affiliations
    Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA

    Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
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  • Wangrong Yang
    Affiliations
    Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
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  • David W. Xiong
    Affiliations
    Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
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  • Parviz Minoo
    Affiliations
    Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
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  • John K. Jain
    Correspondence
    Corresponding author. Tel.: +1 323 226 3008; fax: +1 323 226 2850.
    Affiliations
    Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
    Search for articles by this author

      Abstract

      Purpose

      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.

      Method

      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.

      Conclusion

      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.

      Keywords

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