Contraception
Volume 79, Issue 6 , Pages 469-478, June 2009

Effects of doxycycline on serum and endometrial levels of MMP-2, MMP-9 and TIMP-1 in women using a levonorgestrel-releasing subcutaneous implant☆☆☆

  • Shumei Zhao

      Affiliations

    • Department of Obstetrics and Gynecology, CONRAD Clinical Research Center, Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, VA 23507, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 757 446 7056; fax: +1 757 446 8998.
    • ,
  • Chainarong Choksuchat

      Affiliations

    • Department of Obstetrics and Gynecology, Prince of Songkla University, Songkla, Thailand 90110
    • ,
  • Yueqin Zhao

      Affiliations

    • Epidemiology and Biostatistics Core, Graduate Program of Public Health, Eastern Virginia Medical School, Norfolk, VA 23507, USA
    • ,
  • Susan A. Ballagh

      Affiliations

    • Department of Obstetrics and Gynecology, CONRAD Clinical Research Center, Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, VA 23507, USA
    • ,
  • George A. Kovalevsky

      Affiliations

    • Department of Obstetrics and Gynecology, CONRAD Clinical Research Center, Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, VA 23507, USA
    • ,
  • David F. Archer

      Affiliations

    • Department of Obstetrics and Gynecology, CONRAD Clinical Research Center, Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, VA 23507, USA

Received 5 November 2008; received in revised form 22 December 2008; accepted 23 December 2008. published online 09 February 2009.

Abstract 

Background

Endometrial spotting and/or bleeding (ESB) occurs in levonorgestrel subcutaneous implant (LNG SI) users. Matrix metalloproteinases (MMPs) may play a role in ESB.

Study Design

Women between 18 and 40 years with regular menstrual cycles had a baseline evaluation followed by LNG SI insertion and randomization to doxycycline (DOX; 20 mg) or placebo (PL) twice a day. MMP-2, MMP-9 and tissue inhibitor of MMP-1 (TIMP-1) in serum and the endometrium were estimated at baseline and at 1, 3 and 6 months after insertion.

Results

LNG increased serum MMP-9, while DOX decreased MMP-9 levels compared to PL after 1 month (p<.05). DOX decreased endometrial MMP-9 at 1 and 6 months compared to baseline and PL (p<.05).

DOX increased endometrial TIMP-1 at 6 months compared with baseline and PL (p<.05). MMP-2 levels were unchanged.

Conclusion

LNG SI increased serum MMP-9 and TIMP-1 levels, while DOX decreased both serum and endometrial MMP-9 levels.

Keywords: Doxycycline, Matrix metalloproteinases, Tissue inhibitor of metalloproteinases, Levonorgestrel subcutaneous implant, Endometrium, Bleeding

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☆ The research was supported by NIH Grant R01 HD43175-01.

☆☆ Dr. Shumei Zhao, Dr. Chainarong Choksuchat, Ms. Yueqin Zhao and Dr. George Kovalevsky have no conflicts of interest. Dr. David Archer is a paid consultant for Abbott Laboratories, Agile Therapeutics, Bayer Healthcare, Berlex, ConCert Pharmaceutical, Novo Nordisk, Radius, Schering Plough, Warner Chilcott and Wyeth Laboratories; he has Industry-Supported Research from Bayer Healthcare, Duramed, Organon-Schering Plough, Solvay, Warner Chilcott and Wyeth Laboratories; he receives Direct Industry Lecture Fees from Novo Nordisk, Organon, Schering Plough, Solvay, Upsher-Smith Laboratories and Wyeth Laboratories. Dr. Susan Ballagh is a paid consultant for Contraception Online, Gerson-Lehrman Group, Organon and Wyeth Laboratories; she has Industry-Support Research from Duramed Research, Bayer Healthcare, Conceptus, Pfizer, Organon, Warner-Chilcott and Wyeth Laboratories; she receives Direct Industry Lecture Fees from ARHP, Cardinal Health, Organon and Wyeth Laboratories.

PII: S0010-7824(08)00579-9

doi:10.1016/j.contraception.2008.12.010

Contraception
Volume 79, Issue 6 , Pages 469-478, June 2009

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