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

Contraception. 2009 Jun;79(6):469-78. doi: 10.1016/j.contraception.2008.12.010. Epub 2009 Feb 7.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Double-Blind Method
  • Doxycycline / administration & dosage*
  • Endometrium / drug effects*
  • Endometrium / enzymology
  • Endometrium / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunohistochemistry
  • Infusions, Subcutaneous
  • Levonorgestrel / administration & dosage*
  • Levonorgestrel / adverse effects
  • Matrix Metalloproteinase 2 / blood
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / blood
  • Matrix Metalloproteinase 9 / metabolism*
  • Metrorrhagia / chemically induced
  • Metrorrhagia / drug therapy
  • Metrorrhagia / enzymology
  • Metrorrhagia / metabolism*
  • Prospective Studies
  • Tissue Inhibitor of Metalloproteinase-1 / blood
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism*
  • Young Adult

Substances

  • Tissue Inhibitor of Metalloproteinase-1
  • Levonorgestrel
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Doxycycline