Effect of oral contraceptives and doxycycline on endometrial MMP-2 and MMP-9 activity

Objectives To describe the effect of combined oral contraceptives (COCs) on matrix metalloproteinases MMP-2 and MMP-9 activity and compare MMP activity in women taking a COC with or without doxycycline. Study design Subjects (n= 20) underwent endometrial biopsies (1) in the late luteal phase of a baseline cycle prior to initiating COCs, (2) on days 19-21 while taking COCs in a standard 28-day cycle (7-day hormone-free interval) and (3) on days 26-28 while taking active COCs continuously for a 28-day cycle. During the continuous COC cycle, they were randomized to receive daily subantimicrobial dose doxycycline 40 mg or placebo. Results Compared to baseline, COC treatment increased MMP-2 (p<.001) and MMP-9 (p<.001). MMP activity was lower in subjects taking a COC with doxycycline compared to those receiving placebo although only significantly lower for MMP-2 latent form (p=.002). Conclusions Unscheduled bleeding with COCs may be the result of increased endometrial MMPs. Sample size limitations prevent us from determining how doxycycline affects MMP activity in COC users.