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This version published online on May 16, 2006
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-2789
A more recent version of this article appeared on August 1, 2006
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Submitted on December 20, 2005
Accepted on May 9, 2006

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

K C Lewandowski, J Komorowski, D P Mikhalidis, M Bienkiewicz, B K Tan, C J O'Callaghan, A Lewinski, G Prelevic, and H S Randeva*

Department of Biological Sciences, University of Warwick, UK; Department of Endocrinology & Metabolic Diseases, The Medical University of Lodz, Poland; Department of Quality Control and Radiation Protection, The Medical University of Lodz, Poland; Department of Community Health and Epidemiology, Queen's University, Kingston, Ontario, Canada; Departments of Endocrinology and Clinical Biochemistry, The Royal Free Hospital School of Medicine, London, UK

* To whom correspondence should be addressed. E-mail: hrandeva{at}bio.warwick.ac.uk.

Background: Matrix metalloproteinases (MMPs) are implicated in numerous disease states including cardiovascular disease and cancer. As recent studies have shown a detrimental effect of HRT 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 & Methods: A total of 195 healthy postmenopausal women were assessed: 46 were taking Tibolone (TIB), 47 were taking transdermal estradiol (TRDE), 46 conjugated equine estrogens (CEE), and 56 were not taking any menopausal therapy (CTR). Plasma levels of MMPs- 2 and 9 (MMP-2, MMP-9) and tissue inhibitors of matrix metalloproteinases 1 and 2 (TIMP-1, TIMP-2) were measured by ELISA methods.

Results: MMP-9 levels were significantly higher in the CEE group in comparison to 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 TRD and CTR, and P < 0.001 compared with CEE). MMP-9/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 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.


Key words: matrix metalloproteinases • tissue inhibitors of matrix metalloproteinases • hormone replacement therapy • menopause • Tibolone







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