Raloxifene Archives - Revista Brasileira de Ginecologia e Obstetrícia
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2008;30(4):177-181
DOI 10.1590/S0100-72032008000400004
PURPOSE: to evaluate the expression of Bax antigen in the normal mammary epithelium of premenopausal women treated with raloxifene. METHODS: a randomized double-blind study was conducted in 33 ovulatory premenopausal women with fibroadenoma. Patients were divided into two groups: Placebo, (n=18) and Raloxifene 60 mg, (n=15). The medication was used for 22 days, beginning on the first day of the menstrual cycle. An excisional biopsy was carried out on the 23rd day of the menstrual cycle and a sample of normal breast tissue adjacent to the fibroadenoma was collected and submitted to immunohistochemical study using anti-Bax polyclonal antibody to evaluate the expression of Bax protein. Immunoreaction for Bax was evaluated taking into consideration intensity and fraction of stained cells, whose combination resulted in a final score ranging from 0 to 6. Cases with a final score >3 were classified as positive for Bax. The c2 test was used for statistical analysis (p<0.05). RESULTS: the percentage of positivity of Bax protein expression was 66.7 and 73.3% in Groups A and B, respectively. There was no significant difference in Bax expression between the two groups (p=0.678). CONCLUSIONS: raloxifene, administered for 22 days in the dose of 60 mg/day, did not alter the expression of Bax protein in the breast normal tissue of premenopausal women.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2008;30(4):177-181
DOI 10.1590/S0100-72032008000400004
PURPOSE: to evaluate the expression of Bax antigen in the normal mammary epithelium of premenopausal women treated with raloxifene. METHODS: a randomized double-blind study was conducted in 33 ovulatory premenopausal women with fibroadenoma. Patients were divided into two groups: Placebo, (n=18) and Raloxifene 60 mg, (n=15). The medication was used for 22 days, beginning on the first day of the menstrual cycle. An excisional biopsy was carried out on the 23rd day of the menstrual cycle and a sample of normal breast tissue adjacent to the fibroadenoma was collected and submitted to immunohistochemical study using anti-Bax polyclonal antibody to evaluate the expression of Bax protein. Immunoreaction for Bax was evaluated taking into consideration intensity and fraction of stained cells, whose combination resulted in a final score ranging from 0 to 6. Cases with a final score >3 were classified as positive for Bax. The c2 test was used for statistical analysis (p<0.05). RESULTS: the percentage of positivity of Bax protein expression was 66.7 and 73.3% in Groups A and B, respectively. There was no significant difference in Bax expression between the two groups (p=0.678). CONCLUSIONS: raloxifene, administered for 22 days in the dose of 60 mg/day, did not alter the expression of Bax protein in the breast normal tissue of premenopausal women.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2007;29(10):525-531
DOI 10.1590/S0100-72032007001000006
PURPOSE: to evaluate changes in mammographic breast density in postmenopausal women using raloxifene. METHODS: in this clinical trial, 80 women (mean age=61.1 years) were studied prospectively. Forty patients received 60 mg/day raloxifene, and 40 women comprised the non-treated group (control), paired by age and time of menopause. The treated group was composed of patients with osteoporosis of the lumbar spine. Those with history of breast surgery and users of hormone therapy up to six months prior to the study were excluded. The breast density was assessed qualitatively (subjective) and quantitatively (objective) in two moments, initial and final, after a 6-month follow-up. The 320 mammograms (craniocaudal and oblique) were interpreted qualitatively by the Breast Imaging Reporting and Data System (BI-RADS) classification and quantitatively by digital scanning and computer-assisted segmentation. For statistical analysis t-test, Wilcoxon Mann-Whitney, Spearman correlation and the kappa index were used. RESULTS: on the initial statistical comparison, the groups were considered homogenous for the variables: analyzed age, time of menopause, parity, breast feeding, previous hormonal therapy and body mass index. Baseline breast density, by qualitative and quantitative methods, correlated negatively with the age in both groups (p<0.05). Concerning the other variables, there was no correlation. After six months, no alteration was observed in the mammographic breast density in 38 women of raloxifene group and 38 of the control group, by qualitative method. However, by quantitative method, no alteration was observed in 30 women of the raloxifene group and 27 controls (p>0.05). It was observed a weak agreement rate (kappa=0.25) between the BI-RADS classification and digital scanning/computer-assisted segmentation. CONCLUSIONS: in post-menopausal women with osteoporosis, submitted to raloxifene treatment for six months, no alterations were observed on the mammographic breast density.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2007;29(10):525-531
DOI 10.1590/S0100-72032007001000006
PURPOSE: to evaluate changes in mammographic breast density in postmenopausal women using raloxifene. METHODS: in this clinical trial, 80 women (mean age=61.1 years) were studied prospectively. Forty patients received 60 mg/day raloxifene, and 40 women comprised the non-treated group (control), paired by age and time of menopause. The treated group was composed of patients with osteoporosis of the lumbar spine. Those with history of breast surgery and users of hormone therapy up to six months prior to the study were excluded. The breast density was assessed qualitatively (subjective) and quantitatively (objective) in two moments, initial and final, after a 6-month follow-up. The 320 mammograms (craniocaudal and oblique) were interpreted qualitatively by the Breast Imaging Reporting and Data System (BI-RADS) classification and quantitatively by digital scanning and computer-assisted segmentation. For statistical analysis t-test, Wilcoxon Mann-Whitney, Spearman correlation and the kappa index were used. RESULTS: on the initial statistical comparison, the groups were considered homogenous for the variables: analyzed age, time of menopause, parity, breast feeding, previous hormonal therapy and body mass index. Baseline breast density, by qualitative and quantitative methods, correlated negatively with the age in both groups (p<0.05). Concerning the other variables, there was no correlation. After six months, no alteration was observed in the mammographic breast density in 38 women of raloxifene group and 38 of the control group, by qualitative method. However, by quantitative method, no alteration was observed in 30 women of the raloxifene group and 27 controls (p>0.05). It was observed a weak agreement rate (kappa=0.25) between the BI-RADS classification and digital scanning/computer-assisted segmentation. CONCLUSIONS: in post-menopausal women with osteoporosis, submitted to raloxifene treatment for six months, no alterations were observed on the mammographic breast density.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2007;29(7):335-339
DOI 10.1590/S0100-72032007000700002
PURPOSE: to evaluate the effect of raloxifene on breast cancer angiogenesis of menopausal women. METHODS: sixteen menopausal women with stage II (>3 cm) estrogen receptor positive operable breast cancer were enrolled in this study. Following confirmation of the diagnosis by incisional biopsy, the patients received 60 mg raloxifene daily for 28 days prior to the definitive surgery. Immunohistochemical study was performed on the sample tumors obtained during the biopsy for the diagnosis and evaluation of the status of estrogen receptor and during the definitive surgery. The anti-CD34 monoclonal antibody was used as a marker for endothelial cells. The vascular unit was considered as any endothelial cell or group of cells of a brownish color, clearly separated from adjacent microvessels, tumor cells or other connective tissue, forming or not lumen. Microvessel count was performed in ten fields of each slide using a 40X objective lens (400X magnification). A microscope coupled to a system of capture and analysis of image was used (Imagelab®). Statistical analysis of data was carried out using the paired Student t-test and significance level was established at p<0.05. RESULTS: mean numbers of anti-CD34 antibody-stained microvessels before and after raloxifene treatment were 44.4±3.5 and 22.6±1.6, respectively. A significant reduction in the number of microvessels following raloxifene therapy was observed (p<0.001). CONCLUSIONS: when administered as primary therapy for menopausal women with breast carcinoma, raloxifene significantly reduced tumoral angiogenesis.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2007;29(7):335-339
DOI 10.1590/S0100-72032007000700002
PURPOSE: to evaluate the effect of raloxifene on breast cancer angiogenesis of menopausal women. METHODS: sixteen menopausal women with stage II (>3 cm) estrogen receptor positive operable breast cancer were enrolled in this study. Following confirmation of the diagnosis by incisional biopsy, the patients received 60 mg raloxifene daily for 28 days prior to the definitive surgery. Immunohistochemical study was performed on the sample tumors obtained during the biopsy for the diagnosis and evaluation of the status of estrogen receptor and during the definitive surgery. The anti-CD34 monoclonal antibody was used as a marker for endothelial cells. The vascular unit was considered as any endothelial cell or group of cells of a brownish color, clearly separated from adjacent microvessels, tumor cells or other connective tissue, forming or not lumen. Microvessel count was performed in ten fields of each slide using a 40X objective lens (400X magnification). A microscope coupled to a system of capture and analysis of image was used (Imagelab®). Statistical analysis of data was carried out using the paired Student t-test and significance level was established at p<0.05. RESULTS: mean numbers of anti-CD34 antibody-stained microvessels before and after raloxifene treatment were 44.4±3.5 and 22.6±1.6, respectively. A significant reduction in the number of microvessels following raloxifene therapy was observed (p<0.001). CONCLUSIONS: when administered as primary therapy for menopausal women with breast carcinoma, raloxifene significantly reduced tumoral angiogenesis.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2006;28(2):101-106
DOI 10.1590/S0100-72032006000200005
PURPOSE: to evaluate the effects of conjugated equine estrogens (CEE) and raloxifene (Ral), alone or combined, on the rat endometrium. METHODS: fifty-six adult rats were ovariectomized and randomly divided into seven groups: GCont (control); GCEE (CEE 50 µg/kg); GCEE/25 (CEE 25 µg/kg); GRal/0.75 (Ral 0.75 mg/kg); GRal/0.4 (Ral 0.4 mg/kg); GCEERal (50/0.75) - (CEE 50 µg/kg + Ral 0.75 mg/kg), and GCEE-Ral (25/0.4) - (CEE 25 µg/kg + Ral 0.4 mg/kg). The drugs were orally administered (gavage) for 21 consecutive days. At the end of the experiment, all animals were anesthetized and sacrificed. Fragments of uterus were removed, fixed in 10% formaldehyde and processed for paraffin inclusion. The histological sections were stained by HE and submitted to histomorphometric evaluation. The following parameters were analyzed: thickness of superficial epithelium and number of endometrial glands/mm² and of blood vessels/mm². The data were evaluated using ANOVA followed by the Turkey-Kramer test. RESULTS: in the GCont and only Ral treatment (GRal/0.75 and GRal/0.4) the endometrium showed signals of atrophy. In the groups treated with only CEE signs of endometrial proliferation were observed, mainly in group GCEE/50. Also, there was endometrial proliferation in the groups that received combined CEE and Ral (Ral GCEE (50/0.75) and GCEE-Ral (25/0.4)), but it was more intensive in the animals treated with isolated estrogen than in those that received combined estrogen and raloxifene. CONCLUSION: raloxifene may partially block the action of estrogen on the castrated adult rat endometrium.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2006;28(2):101-106
DOI 10.1590/S0100-72032006000200005
PURPOSE: to evaluate the effects of conjugated equine estrogens (CEE) and raloxifene (Ral), alone or combined, on the rat endometrium. METHODS: fifty-six adult rats were ovariectomized and randomly divided into seven groups: GCont (control); GCEE (CEE 50 µg/kg); GCEE/25 (CEE 25 µg/kg); GRal/0.75 (Ral 0.75 mg/kg); GRal/0.4 (Ral 0.4 mg/kg); GCEERal (50/0.75) - (CEE 50 µg/kg + Ral 0.75 mg/kg), and GCEE-Ral (25/0.4) - (CEE 25 µg/kg + Ral 0.4 mg/kg). The drugs were orally administered (gavage) for 21 consecutive days. At the end of the experiment, all animals were anesthetized and sacrificed. Fragments of uterus were removed, fixed in 10% formaldehyde and processed for paraffin inclusion. The histological sections were stained by HE and submitted to histomorphometric evaluation. The following parameters were analyzed: thickness of superficial epithelium and number of endometrial glands/mm² and of blood vessels/mm². The data were evaluated using ANOVA followed by the Turkey-Kramer test. RESULTS: in the GCont and only Ral treatment (GRal/0.75 and GRal/0.4) the endometrium showed signals of atrophy. In the groups treated with only CEE signs of endometrial proliferation were observed, mainly in group GCEE/50. Also, there was endometrial proliferation in the groups that received combined CEE and Ral (Ral GCEE (50/0.75) and GCEE-Ral (25/0.4)), but it was more intensive in the animals treated with isolated estrogen than in those that received combined estrogen and raloxifene. CONCLUSION: raloxifene may partially block the action of estrogen on the castrated adult rat endometrium.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2004;26(7):573-578
DOI 10.1590/S0100-72032004000700010
PURPOSE: to evaluate the effects of raloxifene on plasma homocysteine concentration and lipid profile in postmenopausal women. METHODS: twenty-four healthy postmenopausal women, aged 50 to 70 years, with osteopenia and/or osteoporosis, were submitted to raloxifene therapy, 60 mg/day, for six months. Plasma homocysteine concentration was determined before and after three and six months of therapy, as well as total cholesterol, HDL-cholesterol LDL-cholesterol and triglyceride levels. Plasma homocysteine was measured by a polarized immunofluorescence assay and serum lipids by the enzymatic and colorimetric method. Data were analyzed statistically by ANOVA, Newman-Keuls test and Pearson's correlation test. RESULTS: a significant decrease in total cholesterol of 15.3% (227.6±56.3 vs 200.6±29.8 vs 192.8±32.1 mg/dl; p<0.001) and LDL-cholesterol of 21.4% (151.4±46.3 vs 122.7±29.4 vs 119.0±28.6 mg/dl; p<0.001), and a significant increase in HDL-cholesterol of 9.5% (44.7±10.8 vs 52.2±12.6 vs 49.0±10.8 mg/dl; p<0.05) were observed. There was no reduction in triglyceride levels (134.9±50.3 vs 127.5±50.0 vs 121.0±36.0 mg/dl; p>0.05). Although not significant, a decrease in homocysteine by 4.5% (11.7±3.0 vs 11.0±2.9 vs 11.2±2.1 muM/l; p>0.05) was observed between the pre-and posttreatment periods, with a significant negative correlation between basal levels and posttreatment percentual reduction (r=-0.71; p<0.0001). CONCLUSIONS: raloxifene treatment, 60 mg/day, for six months caused a significant decrease in total and LDL-cholesterol and an increase in HDL-cholesterol in postmenopausal women. Plasma homocysteine concentration tended to decrease, this effect being more favorable in patients with elevated baseline levels.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2004;26(7):573-578
DOI 10.1590/S0100-72032004000700010
PURPOSE: to evaluate the effects of raloxifene on plasma homocysteine concentration and lipid profile in postmenopausal women. METHODS: twenty-four healthy postmenopausal women, aged 50 to 70 years, with osteopenia and/or osteoporosis, were submitted to raloxifene therapy, 60 mg/day, for six months. Plasma homocysteine concentration was determined before and after three and six months of therapy, as well as total cholesterol, HDL-cholesterol LDL-cholesterol and triglyceride levels. Plasma homocysteine was measured by a polarized immunofluorescence assay and serum lipids by the enzymatic and colorimetric method. Data were analyzed statistically by ANOVA, Newman-Keuls test and Pearson's correlation test. RESULTS: a significant decrease in total cholesterol of 15.3% (227.6±56.3 vs 200.6±29.8 vs 192.8±32.1 mg/dl; p<0.001) and LDL-cholesterol of 21.4% (151.4±46.3 vs 122.7±29.4 vs 119.0±28.6 mg/dl; p<0.001), and a significant increase in HDL-cholesterol of 9.5% (44.7±10.8 vs 52.2±12.6 vs 49.0±10.8 mg/dl; p<0.05) were observed. There was no reduction in triglyceride levels (134.9±50.3 vs 127.5±50.0 vs 121.0±36.0 mg/dl; p>0.05). Although not significant, a decrease in homocysteine by 4.5% (11.7±3.0 vs 11.0±2.9 vs 11.2±2.1 muM/l; p>0.05) was observed between the pre-and posttreatment periods, with a significant negative correlation between basal levels and posttreatment percentual reduction (r=-0.71; p<0.0001). CONCLUSIONS: raloxifene treatment, 60 mg/day, for six months caused a significant decrease in total and LDL-cholesterol and an increase in HDL-cholesterol in postmenopausal women. Plasma homocysteine concentration tended to decrease, this effect being more favorable in patients with elevated baseline levels.
