Expression of matrix metalloproteinase-26 and tissue inhibitor of matrix metalloproteinase-3 and-4 in endometrium throughout the normal menstrual cycle and alteration in users of levonorgestrel implants who experience irregular uterine bleeding

Objective: To determine the expression of matrix metalloproteinase (MMP-26) and tissue inhibitor of MMP (TIMP) in the endometrium of women with normal menstrual cycles compared with users of levonorgestrel implants. Design: Prospective observational study. Setting: Academic research center. Patient(s): Fifty patients with normal menstrual cycles who requested permanent surgical sterilization (tubal ligation) and 35 users of levonorgestrel implants. Intervention(s): Endometrial biopsy. Main Outcome Measure(s): Expression of MMP-26, TIMP-3, and TIMP-4 by immunohistochemistry and semiquantitative analysis of staining intensity by using the H score. Result(s): Endometrium from women with a normal menstrual cycle and users of levonorgestrel implants expresses MMP-26, TIMP-3, and TIMP-4. These substances are present in various types of endometrial cells; expression is strongest in surface and glandular epithelial cells, followed by vascular endothelial and endometrial stromal cells. Inflammatory and immune-related cells also stained strongly for MMP-26 and TIMPs. Semiquantitative analysis of the staining intensity of endometrial epithelial and stromal cells indicated that expression of MMP-26, TIMP-3, and TIMP-4 peaks during the early to mid-luteal phase. Expression of MMP-26 is elevated in users of levonorgestrel implants who experienced irregular uterine bleeding. Conclusion: Endometrial expression of MMP-26 and TIMP-4 is present throughout the menstrual cycle and is elevated during the early to mid-luteal phase in normally cycling women. Further elevations in MMP-26 are seen in users of levonorgestrel implants who experience irregular uterine bleeding. These substances thus seem to play a role in hormonal regulation and endometrial tissue remodeling. (C) 2003 by American Society for Reproductive Medicine.