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The effect of hormone therapy and raloxifene on serum matrix metalloproteinase-2 and -9 in postmenopausal women

Christodoulakos, George E. MD1; Panoulis, Constantinos P. C. MD1; Lambrinoudaki, Irene V. MD1; Botsis, Dimitrios S. MD1; Dendrinos, Spyros G. MD1; Economou, Emanuel PhD2; Creatsas, George C. MD, FACS1

doi: 10.1097/01.GME.0000097848.95550.07

Objective: The aim of the study was to investigate the effect of continuous-combined hormone therapy and raloxifene on the total and active forms of serum matrix metalloproteinase (MMP) -2 and -9.

Design: The study was double-blinded, with a placebo run-in period of 28 to 50 days. Twenty-eight women received either 17β-estradiol 2 mg + norethisterone acetate 1 mg (E2/NETA) or raloxifene HCL 60 mg for a period of 6 months. Total and active forms of MMP-2 and -9 were estimated at baseline and at month 6.

Results: Total MMP-2 increased significantly in both E2/NETA and raloxifene groups (raloxifene baseline: 278.1 ± 18.1 ng/mL; 6 months: 303.1 ± 29.9 ng/mL, P = 0.008) (E2/NETA baseline: 281.9 ± 27.5 ng/mL; 6 months: 298.8 ± 12.7 ng/mL, P = 0.025). Similarly, both treatments increased the active MMP-2 fraction, although only the raloxifene-associated increase acquired significance (raloxifene baseline: 24.9 ± 8.6 ng/mL; 6 months: 31.6 ± 15.3ng/mL, P = 0.045) (E2/NETA baseline: 21.7 ± 5.7 ng/mL; 6 months: 27.4 ± 5.8 ng/mL, P = 0.128). Total as well as active fractions of MMP-9 were not significantly affected by either treatment.

Conclusions: Both E2/NETA and raloxifene increased the total and active MMP-2 serum levels. MMP-9 was not significantly affected by either regimen. Larger, long-term clinical trials are needed to elucidate the effect of HT and raloxifene on MMPs and the possible clinical implications for cardiovascular health.

Continuous-combined hormone therapy, as well as raloxifene, increased matrix metalloproteinase-2 serum levels after 6 months of therapy, but they had no effect on matrix metalloproteinase-9 serum levels.

From the 12nd Department of Obstetrics and Gynecology, University of Athens, Aretaieion Hospital, Athens, Greece; and the 2Department of Cardiology, University of Athens, Ippokrateion Hospital, Athens, Greece.

Received June 26, 2003; revised and accepted September 4, 2003.

Address correspondence to: As. Prof. G. Christodoulakos, 3, Neofytou Douka Street, Athens, GR-10674, Greece. E-mail:

©2004The North American Menopause Society