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.

Effect of hormone replacement therapy and tibolone on serum leptin levels in postmenopausal women.

OBJECTIVE: To evaluate the effect of estrogen replacement therapy (ERT), continuous combined hormone replacement therapy (HRT) and tibolone on serum leptin levels in healthy postmenopausal women. METHODS: Eighty-four healthy postmenopausal women aged 43-63 years were studied prospectively. Hysterectomized women (n = 16) received conjugated equine estrogens (CEE) 0.625 mg. Women with an intact uterus were randomly allocated either to CEE+medroxyprogesterone acetate (CEE/MPA) 5 mg or tibolone 2.5 mg. Serum leptin levels were assessed at baseline and after 6 months of treatment. RESULTS: The three groups did not differ with respect to age, body mass index (BMI) or baseline serum leptin levels. Overweight women (BMI > 25 kg/m2) had higher baseline leptin levels (27.0 +/- 11.4 ng/ml) compared to their lean counterparts (BMI < or = 25 kg/m2; leptin: 16.5 +/- 8.1 ng/ml, P = 0.0001). Neither CEE nor CEE/MPA had any effect on serum leptin levels at the end of 6 months either in overweight or in lean women (overweight: CEE baseline 34.4 +/- 13.3 ng/ml, 6 months 36.9 +/- 15.8, P = 0.89, CEE/MPA baseline 22.4 +/- 9.8 ng/ml, 6 months 26.8 +/- 8.7 ng/ml, P = 0.1; lean: CEE baseline 12.6 +/- 4.4 ng/ml, 6 months 13.2 +/- 5.8 ng/ml, P = 0.36, CEE/MPA baseline 17.2 +/- 10.6 ng/ml, 6 months 18.8 +/- 8.8 ng/ml, P = 0.31). Similarly serum leptin remained unchanged at the end of the study in both lean and overweight women on tibolone (overweight: baseline 22.9 +/- 8.1 ng/ml, 6 months 18.5 +/- 12 ng/ml, P = 0.37; lean: baseline 13.2 +/- 5.6 ng/ml, 6 months 17.3 +/- 8.4 ng/ml). CONCLUSION: BMI is a strong determinant of serum leptin levels in healthy postmenopausal women. Neither ERT/HRT nor tibolone exert any effect on serum leptin after 6 months in lean or overweight postmenopausal women. Further studies are required to verify the exact role of estrogen and tibolone on leptin production and function in postmenopausal women.