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.


METHODS
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 (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 +/- 15.3 ng/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.
Christodoulakos
George E
GE
2nd Department of Obstetrics and Gynecology, University of Athens, Aretaieion Hospital, Athens, Greece. ilambrinoudaki@hotmail.com
Panoulis
Constantinos P C
CP
Lambrinoudaki
Irene V
IV
Botsis
Dimitrios S
DS
Dendrinos
Spyros G
SG
Economou
Emanuel
E
Creatsas
George C
GC
D001161:Arteriosclerosis / Q000097:blood / Q000517:prevention & control*; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage; D005260:Female; D006115:Greece; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000187:drug effects*; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000187:drug effects*; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077563:Norethindrone Acetate; D017698:Postmenopause; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage*; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage*
D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D000077563:Norethindrone Acetate; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D009640:Norethindrone