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Effects of Hormone Replacement Therapy Type and Route of Administration on Plasma Matrix Metalloproteinases and Their Tissue Inhibitors in Postmenopausal Women

Department of Biological Sciences (K.C.L., B.K.T., H.S.R.), University of Warwick, Coventry CV4 7AL, United Kingdom; Departments of Endocrinology and Metabolic Diseases (K.C.L., J.K., A.L.) and Quality Control and Radiation Protection (D.P.M., M.B.), The Medical University of Lodz, 90-419 Lodz, Poland; Department of Community Health and Epidemiology (C.J.O.), Queen’s University, Kingston, Ontario, Canada K7L 3N6; and Departments of Endocrinology and Clinical Biochemistry (G.P.), The Royal Free Hospital School of Medicine, London NW3 2PF, United Kingdom

Address all correspondence and requests for reprints to: Dr. Harpal S. Randeva, M.B.C.H.B., F.R.C.P., Ph.D., Molecular Medicine Group, Department of Biological Sciences, The University of Warwick, Coventry CV4 7AL, United Kingdom. E-mail: hrandeva{at}bio.warwick.ac.uk.

Background: Matrix metalloproteinases (MMPs) are implicated in numerous disease states including cardiovascular disease and cancer. Because recent studies have shown a detrimental effect of hormone replacement therapy on cardiovascular disease and breast cancer, we investigated whether there are any differences in the concentrations of MMPs and their tissue inhibitors (TIMPs) in women receiving various forms of postmenopausal therapy.

Material and Methods: A total of 195 healthy postmenopausal women were assessed: 46 were taking tibolone, 47 were taking transdermal estradiol, 46 were taking conjugated equine estrogens (CEE), and 56 were not taking any menopausal therapy (CTR). Plasma levels of MMP-2 and -9 and TIMP-1 and TIMP-2 were measured by ELISA methods.

Results: MMP-9 levels were significantly higher in the CEE group in comparison with healthy women not receiving menopausal therapy (P < 0.05). In contrast, MMP-9 levels in the tibolone group were significantly lower than in any other group (P < 0.01, compared with transdermal estradiol and CTR, and P < 0.001, compared with CEE). MMP-9 to TIMP-1 ratio was also significantly higher in the CEE, compared with CTR (P < 0.05), and lower in the tibolone group (P < 0.01, compared with all groups). MMP-2 levels were higher in the CEE group, compared with healthy women not receiving any menopausal therapy, and women taking tibolone (P < 0.05).

Conclusions: Our study demonstrates differential effects of various forms of postmenopausal therapy on serum levels of MMP-9 and MMP-2. It remains to be established whether these differences might be associated with differences in risks of cardiovascular disease and cancer in these women.