A 5-year study on the effect of hormone therapy, tibolone and raloxifene on vaginal bleeding and endometrial thickness.

OBJECTIVES: To study the effect of standard and low-dose estrogen-progestin therapy (EPT), tibolone and raloxifene on the incidence of vaginal spotting/bleeding and endometrial thickness over a 5-year period. METHODS: Seven hundred eighty-six postmenopausal women were studied in an open prospective design. Vaginal spotting/bleeding and endometrial thickness as assessed by transvaginal ultrasonography was compared between six categories of women over a 5-year period: three categories in women on continuous combined estrogen-progestin therapy, one category under tibolone, one category under raloxifene and one under no treatment. More specifically, women received tibolone 2.5 mg (N = 204), raloxifene HCl 60 mg (N = 137), conjugated equine estrogens 0.625 mg/medroxyprogesterone acetate 5mg (N = 122), 17beta-estradiol 2mg/norethisterone acetate 1mg (N = 58), 17beta-estradiol 1mg/norethisterone acetate 0.5mg (N = 76) or no therapy (controls, N = 189). Women with suspected endometrial pathology were referred for hysteroscopy. RESULTS: Bleeding/spotting incidence was highest among standard dose EPT users (conjugated equine estrogens 0.625 mg/medroxyprogesterone acetate 5mg: 40.1%, 17beta-estradiol 2mg/norethisterone acetate 1mg: 44.8%, p < 0.001 compared to controls). Low-dose EPT associated with lower incidence of spotting/bleeding (34.1%). The incidence under tibolone and raloxifene was 22.5% and 2.9%, respectively, while 3.2% of women not receiving therapy reported vaginal spotting/bleeding. Mean endometrial thickness was not significantly affected in any of the groups studied. The drop-out rate due to spotting/bleeding was higher in the two higher dose EPT regimens. After logistic regression analysis, age at baseline was the only significant predictor of subsequent spotting/bleeding (b = -0.25, S.E. = 0.09, p = 0.006), while menopausal age and pre-treatment serum FSH had marginal significance. CONCLUSIONS: EPT, tibolone and raloxifene do not appear to associate with significant changes in endometrial thickness in the majority of cases. The low-dose EPT regimen associated with a decreased incidence of unscheduled spotting/bleeding compared to the standard dose regimens. Tibolone expressed a favorable endometrial profile, as seen in its effect on unscheduled spotting/bleeding and mean endometrial thickness. Raloxifene associated with the lowest incidence in S/B and the lowest drop-out rate.s.

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 (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.