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

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 17beta-estradiol 2 mg + norethisterone acetate 1 mg (E-2/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) (E-2/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+/-15.3 ng/mL, P=0.045) (E-2/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 E-2/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.