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.


METHODS
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.


CONCLUSIONS
LNG SI increased serum MMP-9 and TIMP-1 levels, while DOX decreased both serum and endometrial MMP-9 levels.
Zhao
Shumei
S
Department of Obstetrics and Gynecology, CONRAD Clinical Research Center, Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, VA 23507, USA. zhaos@evms.edu
Choksuchat
Chainarong
C
Zhao
Yueqin
Y
Ballagh
Susan A
SA
Kovalevsky
George A
GA
Archer
David F
DF
D000328:Adult; D004311:Double-Blind Method; D004318:Doxycycline / Q000008:administration & dosage*; D004717:Endometrium / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D055104:Infusions, Subcutaneous; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000009:adverse effects; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000378:metabolism*; D008796:Metrorrhagia / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D011446:Prospective Studies; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood / Q000378:metabolism*; D055815:Young Adult
D019715:Tissue Inhibitor of Metalloproteinase-1; D016912:Levonorgestrel; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D004318:Doxycycline