Effects of doxycycline on serum and endometrial levels of MMP-2, MMP-9 and TIMP-1 in women using a levonorgestrel-releasing subcutaneous implant☆☆☆
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.
aDepartment of Obstetrics and Gynecology, CONRAD Clinical Research Center, Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, VA 23507, USA
bDepartment of Obstetrics and Gynecology, Prince of Songkla University, Songkla, Thailand 90110
cEpidemiology and Biostatistics Core, Graduate Program of Public Health, Eastern Virginia Medical School, Norfolk, VA 23507, USA
☆ 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.
ABSTRACT