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

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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.




Kaneshiro, B., Edelman, A., Dash, C., Pandhare, J., Soli, F. M., & Jensen, J. T. (2016). Effect of oral contraceptives and doxycycline on endometrial MMP-2 and MMP-9 activity. Contraception, 93(1), 65–69. https://doi.org/10.1016/j.contraception.2015.09.006

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