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1.
The effects of selective estrogen receptor modulator treatment following hormone replacement therapy on elderly postmenopausal women with osteoporosis.
Hayashi, T, Ina, K, Maeda, M, Nomura, H
Nitric oxide : biology and chemistry. 2011;(4):199-203
Abstract
OBJECTIVES A comparison between the atheroprotective and osteoprotective effects of the selective estrogen receptor modulator (SERM) raloxifene and those of hormone replacement therapy (HRT) has not been made in elderly women. METHODS A randomized prospective controlled trial was performed in a cohort of 32 elderly Japanese women with osteoporosis receiving HRT (estriol plus medroxyprogesterone) for more than 1 year. In 16 randomly selected subjects, HRT was changed to raloxifene therapy (60mg/day, 71.4±3.4 years, SERM group). The other 16 patients were continued on HRT (71.8±2.9 years, HRT group). As a control group, 14 subjects were enrolled, did not take any medications and were age-matched to experimental patients (72.5±3.3 years, control group). Plasma lipids, TNFα, adiponectin, NO metabolites (NOx:NO2(-) and NO3(-)), cyclicGMP and bone-mineral density (BMD) were evaluated at baseline and at 26 and 52 weeks after enrollment. RESULTS SERM (Raloxifene) increased high-density-lipoprotein cholesterol levels and tended to decrease low-density-lipoprotein cholesterol levels (P=0.058) compared with baseline. Adiponectin, NOx and cGMP levels were significantly increased after 6 months compared with baseline or the HRT group. TNFα was decreased by raloxifene. In control subjects, no significant changes were observed in any of these markers. Bone-mineral density was higher at baseline in the raloxifene and HRT groups than in the control group, and BMD increased 12 months after baseline in the HRT and control group. CONCLUSION SERM improved BMD and endothelial function in elderly postmenopausal women with osteoporosis who had received HRT, and these effects were comparable to or slightly stronger than those of HRT. Changes in adiponectin and TNFα may underlie the improvements in endothelial function, such as NO signaling.
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2.
The effect of alendronate, risedronate, and raloxifene on renal functions, based on the Cockcroft and Gault method, in postmenopausal women.
Yanik, B, Bavbek, N, Yanik, T, Inegöl, I, Kanbay, M, Turgut, FH, Uz, E, Akçay, A
Renal failure. 2007;(4):471-6
Abstract
BACKGROUND Oral alendronate, risedronate, and raloxifene are effective treatment options in the management of postmenopausal osteoporosis. There is little previously reported about the renal safety profiles of these three agents in osteoporosis. We aimed to assess the risk of renal toxicity associated with oral alendronate, risedronate, and raloxifene in the treatment of osteoporosis, prospectively. METHODS One hundred and twenty-seven patients with osteoporosis and osteopenia according to lumbar or femoral-neck bone mineral density t score were enrolled in the study. The patients were randomized to alendronate 70 mg once weekly (n = 47), risedronate 35 mg once weekly (n = 44), or raloxifene 60 mg per day (n = 36) for one year. Preliminary screening included medical history, physical examination, lumbar and femoral bone mineral densitometry measurement, and blood biochemical tests, including renal function tests. The biochemical markers were then assessed at the end of 12 months. RESULTS There was no significant difference between basal and final renal function parameters of each group. Also these parameters did not differ between the three groups after 12 months of treatment period. CONCLUSIONS These results demonstrate that alendronate, risedronate, and raloxifene are all safe drugs for renal functions in the treatment of osteoporosis.
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3.
Comparison of the effects of raloxifene and low-dose hormone replacement therapy on bone mineral density and bone turnover in the treatment of postmenopausal osteoporosis.
Dane, C, Dane, B, Cetin, A, Erginbas, M
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2007;(7):398-403
Abstract
OBJECTIVE The aim of the present study was to compare the effects of raloxifene and low-dose hormone replacement therapy (HRT) on bone mineral density (BMD) and bone turnover markers in the treatment of postmenopausal osteoporosis. METHODS Forty-two postmenopausal osteoporotic women, who were randomized to receive raloxifene 60 mg or estradiol 1 mg/norethisterone acetate 0.5 mg daily for 1 year, were studied. All women received calcium 600 mg/day and vitamin D 400 IU/day. BMD and markers of bone turnover were measured at baseline and at 12 months. RESULTS After 12 months of treatment, there were statistically significant increases in BMD in both groups at all sites (all p < 0.05). For the lumbar spine, the increase in BMD was 2.3% for raloxifene compared with 5.8% for low-dose HRT and corresponding values for total body BMD were 2.9% for raloxifene and 4.6% for low-dose HRT; the increases being significantly greater in the low-dose HRT group (p < 0.001 and p = 0.02, respectively). Although the increase in BMD at the hip was significant for both raloxifene (2.1%) and low-dose HRT (3.2%) compared with baseline, the difference between the two regimens did not reach statistical significance. The decrease in serum C-terminal telopeptide fragment of type I collagen and serum osteocalcin levels for the low-dose HRT group (-53% and -47%, respectively) was significantly greater than for the raloxifene group (-23% and -27%, respectively; both p < 0.01). CONCLUSIONS In postmenopausal women with osteoporosis, low-dose HRT produced significantly greater increases in BMD of the lumbar spine and total body and greater decreases in bone turnover than raloxifene at 12 months.
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4.
A comparison of the effects of raloxifene and conjugated equine estrogen on bone and lipids in healthy postmenopausal women.
Reid, IR, Eastell, R, Fogelman, I, Adachi, JD, Rosen, A, Netelenbos, C, Watts, NB, Seeman, E, Ciaccia, AV, Draper, MW
Archives of internal medicine. 2004;(8):871-9
Abstract
BACKGROUND Although many studies have assessed the effects of estrogen and raloxifene hydrochloride on bone mineral density and serum lipid concentrations, there are few direct comparative data. METHODS Randomized placebo-controlled trial for 3 years, intention-to-treat analysis. Six hundred nineteen postmenopausal women with prior hysterectomy (mean age, 53.0 years) were studied in 38 centers in Europe, North America, Australasia, and South Africa. They were randomized to 60 mg/d or 150 mg/d of raloxifene, 0.625 mg/d of conjugated equine estrogen (CEE), or placebo. Bone density of the lumbar spine and proximal femur, biochemical markers of bone turnover, and fasting serum lipid concentrations were assessed for 3 years. RESULTS Compared with baseline, bone density in the lumbar spine progressively declined by 2.0% in the placebo group (P <.05), was stable in the 2 raloxifene groups, and increased 4.6% in the subjects receiving CEE (P <.001). Effects in both raloxifene groups were different from those observed in the CEE and placebo groups (P <.001). Bone density in the total hip showed similar results. Conjugated equine estrogen produced significantly greater depression of serum osteocalcin, bone-specific alkaline phosphatase, and urine C-telopeptide, compared with raloxifene. Each of the active treatments caused comparable depression of low-density lipoprotein cholesterol below placebo levels (P <.001 at most time points). Raloxifene did not affect high-density lipoprotein cholesterol, whereas CEE increased it by 13.4% compared with placebo at 3 years (P <.001). Triglyceride concentrations increased 24.6% in the CEE group at 3 years (P <.003), a significantly greater change than in the raloxifene groups, which were 4.9% and 8.0% above baseline (P < or =.002) but not different from placebo. Urinary incontinence was reported in 11 women receiving CEE, but in only 1 or 2 in each of the other groups (P < or =.01 compared with the other groups). Hernias occurred less frequently in those receiving 150 mg/d of raloxifene or CEE (P =.03 vs placebo). CONCLUSIONS Raloxifene and CEE have beneficial effects on bone density and bone turnover, although effects of CEE are more marked. Raloxifene and CEE produce different patterns of lipid responses and have distinct adverse effect profiles.
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5.
Comparative vascular effects of hormone replacement therapy and raloxifene in women at increased cardiovascular risk.
Cerquetani, E, Vitale, C, Mercuro, G, Fini, M, Zoncu, S, Rosano, GM
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2004;(6):291-8
Abstract
Hormone replacement therapy (HRT) improves endothelial function in postmenopausal women while the effects of raloxifene, a selective estrogen receptor modulator, are still under debate. The aim of this study was to evaluate endothelium-dependent flow-mediated vasodilatation in the brachial artery and plasma levels of nitrite, nitrate and endothelin-1 in 20 postmenopausal women with increased cardiovascular risk treated with either HRT or raloxifene for 4 weeks in a randomized double-blind single cross-over study. Patients had an endothelium-dependent flow-mediated dilatation of 4% prior to initiation of the study. Treatment with HRT resulted in a 67% increase in dilatation compared with baseline (from a 7.4% increase to a 12.4% increase, p < 0.01). Raloxifene treatment resulted in no change in vasodilatation from baseline. Endothelium-dependent dilatation was significantly improved by HRT compared with raloxifene treatment (12.4+/-0.6% vs. 6.1+/-2.0%; p < 0.01). Compared with baseline values, nitrate plus nitrite levels increased significantly (p < 0.05) with HRT but not with raloxifene. Similarly, endothelin-1 decreased from baseline with both treatments, but only the HRT-induced decrease was statistically significant (p < 0.05). In conclusion, HRT improved endothelial function and reduced plasma levels of endothelin-1 in postmenopausal women at risk of coronary artery disease. These beneficial effects were not shared by raloxifene.
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6.
The effects of raloxifene and simvastatin on plasma lipids and endothelium.
Sbarouni, E, Flevari, P, Kroupis, C, Kyriakides, ZS, Koniavitou, K, Kremastinos, DT
Cardiovascular drugs and therapy. 2003;(4):319-23
Abstract
PURPOSE Raloxifene is a selective estrogen receptor modulator and an attractive alternative to estrogen replacement as it obviates the need for a progestin and does not increase C-reactive protein levels. We compared the effects of simvastatin and raloxifene treatments on the lipid profile, the levels of adhesion molecules and the endothelium dependent and independent vasoreactivity. SUBJECTS & METHODS We treated 12 postmenopausal women with hypercholesterolemia and coronary artery disease with raloxifene 60 mg/day and simvastatin 20 mg/day in a randomized, double-blind, crossover study. Each treatment period was 8 weeks long with a 4-week washout interval. Plasma lipids and cellular adhesion molecules were evaluated and peripheral blood flow studies with venous occlusion plethysmography were performed. RESULTS Both simvastatin and raloxifene significantly reduced total [33% (27-40), 12% (0-24)] and LDL [44% (36-52), 16% (0-33)] cholesterol compared to baseline values (p < 0.05) but simvastatin was more effective than raloxifene (p < 0.005). None of the treatments had any significant effect on HDL cholesterol and triglyceride levels. Only raloxifene significantly reduced Lp(a) [18% (1-36)] and ICAM-1 [17% (8-25)] and VCAM-1 [24% (15-33)] plasma levels compared to baseline (p = 0.019, p < 0.0001 and p = 0.003, respectively). Hyperemic blood flow response on raloxifene was significantly higher compared to baseline [52% (0-105)], (p < 0.05), whereas no significant change was noted on simvastatin. Endothelium independent blood flow induced by nitroglycerine was not influenced by either active treatment. CONCLUSIONS Raloxifene administration is associated with lower ICAM-1, VCAM-1 and Lp(a) plasma levels and enhanced endothelium dependent dilation compared to simvastatin although simvastatin is more powerful in total and LDL cholesterol reduction.
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7.
[A randomised clinical trial to study the effects of raloxifene hydrochloride on bone mineral density, biochemical markers of bone metabolism and serum lipids in postmenopausal women].
Zheng, SR, Wu, YY, Zhang, ZL, Yang, X, Hui, Y, Zhang, Y, Chen, SL, Den, WH, Liu, H, Ekangaki, A, et al
Zhonghua fu chan ke za zhi. 2003;(4):226-9
Abstract
OBJECTIVE To determine the effect of raloxifene hydrochloride (RLX) on bone mineral density (BMD), biochemical markers of bone metabolism and lipid metabolism in Chinese postmenopausal women. METHODS This was a multicenter, randomized, double blind placebo controlled study in China with a total of 204 postmenopausal women [mean age (60 +/- 5) years (x +/- s) and weight (63 +/- 9) kg (x +/- s)] treated with either RLX 60 mg (n = 102) or placebo (n = 102) daily for 12 months. BMD, serum lipid and bone markers were determined before and after drug administration. RESULTS Compared to placebo, RLX produced a significant increase in both total lumbar spine and total hip BMD. For the lumbar spine, percentage increase in total BMD was 2.30% with RLX compared to a decrease of 0.08% with placebo (P < 0.001). Corresponding values for total hip BMD were 2.46% increase for RLX and 1.07% for placebo (P < 0.05). For biochemical markers of bone metabolism, serum osteocalcin and C-telopeptide, percentage decrease were 27.6% and 24.0% in raloxifene-treated subjects. Corresponding values in placebo were 10.6% decrease and 15.8% increase (RLX compared to placebo, both P < 0.001). For total cholesterol and low-density lipoprotein cholesterol, percentage decrease were 6.4% and 34.6% in the raloxifene-treated group. Corresponding values in placebo were 1.4% increase and 19.1% decrease (RLX compared to placebo, both P < 0.001). No differences were found for high-density lipoprotein cholesterol or triglyceride levels between the two groups. Only 5 subjects discontinued early due to an adverse event (3 in the RLX group and 2 in the placebo group). CONCLUSIONS This study confirms that RLX exerts positive effects on the skeleton, increasing BMD and decreasing biochemical markers of bone metabolism, and decreased total cholesterol and low-density lipoprotein cholesterol in postmenopausal women in China.
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8.
Raloxifene does not modify insulin sensitivity and glucose metabolism in postmenopausal women.
Cagnacci, A, Paoletti, AM, Zanni, A, Arangino, S, Ibba, G, Orrù, M, Melis, GB, Volpe, A
The Journal of clinical endocrinology and metabolism. 2002;(9):4117-21
Abstract
Insulin sensitivity (Si), glucose tolerance, and lipid metabolism were investigated in osteopenic postmenopausal women before and after 6 months of treatment with raloxifene (60 mg/d) or placebo. In a group of women (n = 34), glucose metabolism was evaluated by means of an oral glucose tolerance test (75 g). In another group of women (n = 24), Si and peripheral glucose utilization not dependent on insulin were evaluated by means of a frequently sampled iv glucose tolerance test associated with the minimal model method. No metabolic modification was observed in women receiving placebo. Raloxifene did not significantly modify high density lipoprotein-cholesterol and triglycerides, whereas it significantly decreased low density lipoprotein (LDL) cholesterol (4.84 +/- 0.34 mmol/liter vs. 3.83 +/- 0.49 mmol/liter; P = 0.014) and LDL/high density lipoprotein cholesterol ratio (3.21 +/- 0.31 mmol/liter vs. 2.46 +/- 0.44 mmol/liter; P = 0.012). Fasting levels and responses to the oral glucose tolerance test of glucose, insulin, C-peptide, and C-peptide/insulin were not modified by raloxifene. Similarly, raloxifene did not modify Si (4.22 +/- 4.1 vs. 5.13 +/- 1.75), or insulin (0.025 +/- 0.003 vs. 0.019 +/- 0.002). The present data show that in osteopenic postmenopausal women raloxifene reduces LDL levels but does not modify insulin sensitivity and glucose metabolism.
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9.
Raloxifene versus continuous combined estrogen/progestin therapy: densitometric and biochemical effects in healthy postmenopausal Taiwanese women.
Tsai, KS, Yen, ML, Pan, HA, Wu, MH, Cheng, WC, Hsu, SH, Yen, BL, Huang, KE
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2001;(12):1020-5
Abstract
We treated 116 healthy postmenopausal women (age 47-66 years, mean 57 years) in Taiwan with either raloxifene (RLX) 60 mg (n = 92) or 0.625 mg conjugated equine estrogen plus 5 mg medroxyprogesterone acetate (CCEP, n = 24) daily for 12 months in a randomized, double-masked, active-controlled fashion. The results showed that both regimens increased bone mineral density (BMD) at hip sites (means: RLX 2.5-4.9%, CCEP 4.6-7.9%, all p<0.005 compared with baseline), and the difference between the two regimens was not significant. The spinal BMD increased significantly in both groups (1.4% with RLX and 6.0% with CCEP, both p<0.01), and more with CCEP (p<0.003). Osteocalcin levels and urinary type I collagen C-telopeptide/creatinine ratios decreased significantly in both regimens, but the decreases were significantly larger with CCEP. Compared with baseline, both RLX and CCEP decreased the total cholesterol (median 4.9% and 8.6% respectively, p<0.001) and LDL-cholesterol (median 11% and 19% respectively, p<0.001), and increased HDL-cholesterol (median 8.6% and 10.7% respectively, p<0.01). Both regimens increased triglyceride levels (median 3.2% and 18.9% respectively, both p<0.05), although to a lesser extent with RLX than with CCEP (p<0.05). Only 3 subjects (3.3%) reported vaginal bleeding in the RLX group, as compared with 31% (7/22) with CCEP (p<0.05). We conclude that in healthy, postmenopausal Taiwanese women, RLX 60 mg given daily has favorable results in BMD, bone turnover and serum lipids, although the dosage we used showed a potency less than that of conventional CCEP.
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10.
Effects of estrogen and the selective estrogen receptor modulator raloxifene on markers of inflammation in postmenopausal women.
Blum, A, Schenke, WH, Hathaway, L, Mincemoyer, R, Csako, G, Waclawiw, MA, Cannon, RO
The American journal of cardiology. 2000;(8):892-5