Endometrial bleeding in hormone replacement therapy users: preliminary findings regarding the role of matrix metalloproteinase 9 (MMP-9) and tissue inhibitors of MMPs

Objective: To establish the effect of hormone replacement therapy (HRT) on the expression of matrix metalloproteinase 9 (MMP-9) and the tissue inhibitor of MMPs, TIMP-1, in the endometrium of postmenopausal and perimenopausal women. Design: Prospective observational study. Setting: United Kingdom teaching hospital. Patient(s): Thirty-one perimenopausal and postmenopausal HRT recipients, with a control group of eight postmenopausal women not undergoing HRT. Intervention(s): Prospective record of bleeding patterns and endometrial biopsy. Main Outcome Measure(s): Endometrial histology, bleeding patterns, MMP-9, and TIMP-1 expression. Result(s): MMP-9 and TIMP-1 are expressed in benign postmenopausal endometrium. Expression of both molecules is reduced in HRT recipients compared with non-HRT recipients. Conclusion(s): Exposure to HRT appears to alter endometrial expression of MMP-9 and TIMP-1 and also the local balance between these molecules. This alteration may promote breakdown of the endometrial extracellular matrix and blood vessels and hence bleeding. (C) 2001 by American Society for Reproductive Medicine.