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

Contraception. 2016 Jan;93(1):65-9. doi: 10.1016/j.contraception.2015.09.006. Epub 2015 Sep 25.

Abstract

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 40mg 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.

Keywords: Combined oral contraceptives; Doxycycline; Endometrial biopsy; Matrix metalloproteinase-2 (MMP-2); Matrix metalloproteinase-9 (MMP-9).

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Anti-Bacterial Agents / pharmacology*
  • Contraceptives, Oral, Combined / adverse effects
  • Contraceptives, Oral, Combined / pharmacology*
  • Doxycycline / pharmacology*
  • Drug Therapy, Combination
  • Endometrium / drug effects
  • Endometrium / enzymology*
  • Female
  • Humans
  • Matrix Metalloproteinase 2 / drug effects*
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / drug effects*
  • Matrix Metalloproteinase 9 / metabolism
  • Metrorrhagia / chemically induced
  • Middle Aged
  • Prospective Studies
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Contraceptives, Oral, Combined
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Doxycycline