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

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 (pb.05). DOX decreased endometrial MMP-9 at 1 and 6 months compared to baseline and PL (pb.05). DOX increased endometrial TIMP-1 at 6 months compared with baseline and PL (pb.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. © 2009 Published by Elsevier Inc.