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.

Concentrations of soluble Fas in maternal serum and amniotic fluid during uncomplicated pregnancies.

OBJECTIVE: To determine, during normal pregnancy, maternal serum (MS) and amniotic fluid (AF) concentrations of soluble Fas (sFas), an apoptosis-suppressing molecule that might play a role in the apoptotic process. Soluble Fas levels might explain existing immunotolerance, fetal well being, and rupture of membranes at term. METHODS: Sixty-six healthy, nonsmoking, pregnant women (mean age 32.6 +/- 4.8 years) with uncomplicated singleton pregnancies (15 in the first trimester, 30 in the second trimester, and 21 at term vaginal delivery) and 20 healthy nonpregnant women (mean age 32.5 +/- 3.8 years) were included in the study. RESULTS: MS and AF sFas concentrations were measured by a sandwich enzyme-linked immunosorbent assay, and parametric tests were used in the statistical analysis.MS and AF sFas concentrations significantly depended on gestational age (P < .0008 and P < .0002, respectively). MS concentrations were significantly lower in the first trimester than those in the second trimester (P <.003), those at term (P < .03), and those in nonpregnant controls (P < .005). AF concentrations decreased significantly at term compared with those in the second trimester (P < .0003). AF sFas concentrations in the second trimester and at term were significantly lower than respective MS concentrations (P < .00001). CONCLUSION: MS sFas concentrations decreased significantly in the first trimester of pregnancy, possibly affecting semiallograft tolerance. In the second trimester, concentrations return to control levels and remain unchanged until delivery. AF sFas concentrations decrease at term compared with the second trimester, possibly indicating increased apoptosis in preparation for rupture of membranes.