Safety and Adverse Effects Associated With Raloxifene: Multiple Outcomes of Raloxifene Evaluation

Grady, Deborah; Ettinger, Bruce; Moscarelli, E; Plouffe, Leo; Sarkar, Somnath; Ciaccia, Angelina V.; Cummings, Steven R.

doi:10.1097/01.aog.0000137349.79204.b8

Cited by 141 publications

(91 citation statements)

References 31 publications

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“…Overall, the incidences of AEs, serious AEs, and discontinuations due to AEs with bazedoxifene were not different from those (14)(15)(16)(17) ; however, this study found no significant differences in the incidence of hot flushes between the bazedoxifene and placebo treatment groups. This finding is consistent with the low incidence of hot flushes seen with raloxifene in postmenopausal Japanese women (11) and reports that Asian women are generally less likely to report hot flushes and other menopausal symptoms than white women.…”

Section: Discussioncontrasting

confidence: 68%

Effects of bazedoxifene on bone mineral density, bone turnover, and safety in postmenopausal japanese women with osteoporosis

Itabashi¹,

Chines

Miki

et al. 2010

Journal of Bone and Mineral Research

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This randomized, double-blind, placebo-controlled, dose-response late phase 2 study evaluated the efficacy and safety of bazedoxifene in postmenopausal Japanese women 85 years of age or younger with osteoporosis. Eligible subjects received daily treatment with oral doses of bazedoxifene 20 or 40 mg or placebo for 2 years. Efficacy assessments included bone mineral density (BMD) at the lumbar spine and other skeletal sites, bone turnover marker levels, lipid parameters, and incidence of new fractures. Of 429 randomized subjects, 387 were evaluable for efficacy, and 423 were included in the safety analyses (mean age, 64 years). At 2 years, the mean percent changes from baseline in lumbar spine BMD were significantly greater with bazedoxifene 20 and 40 mg (2.43% and 2.74%, respectively) than with placebo (À0.65%, p < .001 for both). Both bazedoxifene doses significantly improved BMD at the total hip, femoral neck, and greater trochanter compared with placebo ( p < .001 for all). Decreases in bone turnover markers were observed with bazedoxifene 20 and 40 mg as early as 12 weeks ( p < .05 for all) and were sustained throughout the study. Total and low-density lipoprotein cholesterol levels were significantly decreased from baseline with both bazedoxifene doses compared with placebo ( p < .05 for all). Incidences of new vertebral and nonvertebral fractures were similar among the bazedoxifene and placebo groups. Overall, the incidence of adverse events with bazedoxifene 20 and 40 mg was similar to that with placebo. Bazedoxifene significantly improved BMD, reduced bone turnover, and was well tolerated in postmenopausal Japanese women with osteoporosis. ß

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Section: Discussioncontrasting

confidence: 68%

Effects of bazedoxifene on bone mineral density, bone turnover, and safety in postmenopausal japanese women with osteoporosis

Itabashi¹,

Chines

Miki

et al. 2010

Journal of Bone and Mineral Research

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“…15 R has not been linked to cataract formation. 12,14,16 Results from the present study using RhREC show that E2 induced a reduction of the level of VEGF and PEDF. Suzuma and colleagues 25 reported an increase of VEGF in response to E2 treatment of bovine retinal endothelial cells, and Mueller and colleagues 28 reported an increase in VEGF in human endometrial cells in response to E2.…”

Section: Discussionmentioning

confidence: 54%

“…15 Investigation of R at 60 or 120 mg/day compared to placebo in a study of 7,705 women for a mean of 3.3 years has demonstrated no increased risk of cataract. 16 The updated STAR report demonstrated a slightly higher risk of invasive breast cancer with R when compared to T, but once again revealed an enhanced safety profile with R as was demonstrated in the first study. R was reported to maintain 76% of the effectiveness of T, which correlates to a 38% reduction in invasive breast cancer compared to no treatment.…”

mentioning

confidence: 80%

Effects of Tamoxifen Versus Raloxifene on Retinal Capillary Endothelial Cell Proliferation

Grigsby

Parvathaneni

Almanza

et al. 2011

Journal of Ocular Pharmacology and Therapeutics

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Purpose: Endothelial cell proliferation in angiogenesis is active in conditions such as cancers and diabetic retinopathy. Tamoxifen (T) and raloxifene (R) have been compared in numerous studies as a prophylaxis for breast cancer, and T is used to treat breast cancer. T, unlike R, has been linked to an increase in uterine cancers, thrombo-embolic events, and cataract. The purpose of our study was to evaluate the efficacies of T and R in reducing estrogen-induced retinal capillary endothelial cell proliferation. Methods: Rhesus monkey retinal capillary endothelial cells (ATCC RF/6A) were used to assay cell proliferation when treated with 0.0, 0.1, 1.0, and 10.0 nM 17 b estradiol (E2) for 24 and 48 h. Viable cells were counted using a Neubauer hemocytometer with a trypan blue exclusion method to determine the number of viable cells. Cell counts were also performed using 1.0 nM E2 with 0.01, 0.1, 1.0, and 10.0 nM concentrations of either T or R. Cell medium, collected at 24 h, was evaluated for vascular endothelial growth factor and pigment epithelium-derived factor. Results: Viable cells were significantly greater in cultures treated with 1.0 or 10.0 nM E2, compared to cells treated with 0.0 or 0.1 nM E2 both at 24 and 48 h. Viable cell counts were reduced significantly in cultures treated with 0.1, 1.0, or 10.0 nM T or R in addition to the 1.0 nM E2. Cell counts were not significantly different when comparing equal concentrations of T and R, that is, 1.0 nM E2 + 1 nM T or R. Vascular endothelial growth factor and pigment epithelium-derived factor protein/10,000 cells was reduced by 1.0 nM E2, but returned to higher levels with the introduction of T and R to growth media. Conclusions: T and R showed similar potency in inhibiting estrogen-induced retinal capillary endothelial cell proliferation. Considering drug safety profiles, our results, when extended to animals and humans, suggest that R is preferable to T in treating angiogenic retinal diseases. Further studies on the signaling mechanism of estrogen-induced endothelial cell proliferation may lead to new treatment strategies in the treatment of ocular angiogenic diseases.

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“…Raloxifene increases the risk of VTE similarly to what has been observed with tamoxifen and E use in postmenopausal women (4,(12)(13)(14). In the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, the risk of venous thromboembolic disease (deep venous thrombosis or pulmonary embolism) was found to be 3.1 times higher (95% confidence interval, 1.5 to 6.2) in women assigned to the raloxifene group than to the placebo group.…”

Section: Discussionmentioning

confidence: 74%

Procoagulant state after raloxifene therapy in postmenopausal women

Azevedo

Franco

Baggio

et al. 2005

Fertility and Sterility

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Objective: To investigate the effects of raloxifene on the hemostatic system in postmenopausal women. Design: A prospective longitudinal study. Setting: Outpatient clinic of the Faculty of Medicine of Ribeirão Preto, Brazil. Patient(s): Sixteen postmenopausal women aged 56.8 Ϯ 5.9 years (mean Ϯ SD). Intervention(s): Raloxifene hydrochloride (60 mg once daily) was administered orally for a period of 6 months. Main Outcome Measure(s): Plasma activities of coagulation factors (II, V, VII, VIII, IX, X, XI, XII, and fibrinogen), prothrombin-derived fragment 1ϩ2, and activated protein C (APC) sensitivity ratio were measured at baseline and after 1, 3, and 6 months of treatment. Result(s): Factor VIII activity increased by 17.1% and 26.9% at 3 and 6 months of treatment, respectively, compared with baseline. Factor XI and FXII activities significantly increased by 10.9% and 43.1%, respectively, after 6 months compared with baseline. A significant reduction of APC sensitivity ratio also was observed after 6 months of treatment. Conclusion(s):A procoagulant state characterized by increased factor VIII, XI, and XII plasma levels and by reduced APC sensitivity was observed after raloxifene therapy in post-menopausal women. (Fertil Steril 2005; 84:1680 -4. ©2005 by American Society for Reproductive Medicine.)Key Words: Climacteric, hemostatic system, raloxifene, SERMs Raloxifene is a selective estrogen receptor modulator and exerts tissue-selective effects similar to those of estrogen (E) on bone and serum lipids, without any apparent stimulatory effect on mammary and uterine tissues (1-5). The effect of raloxifene on the cardiovascular system in postmenopausal women has been studied, and the favorable results have been explained mainly by its effects on metabolic changes in lipoproteins, homocysteine, and improved endothelium-dependent vasomotricity, preventing arteriosclerosis and acting as a vasodilating agent (6 -9).Despite these benefits, raloxifene therapy increases the risk of venous thromboembolism (VTE) by approximately threefold, a similar effect to that observed with hormone therapy (HT) (4). Although a large body of data supports a procoagulant state related to E administration, there are few published data on the effect of raloxifene on hemostatic parameters in postmenopausal women. In an article published elsewhere (10), we reported that raloxifene therapy is associated with a significant reduction in plasma antithrombin activity, suggesting that this effect may contribute to a procoagulant state and partly explain the increased risk of VTE in raloxifene users. Here, we report the results of a longitudinal study assessing the effects of raloxifene on other hemostatic parameters in healthy postmenopausal women. MATERIALS AND METHODS Study SubjectsSixteen postmenopausal women were enrolled in a prospective longitudinal study. General characteristics of the subjects were as follows (values given as mean Ϯ SD): age, 56.8 Ϯ 5.9 years; duration of menopause, 9.3 Ϯ 5.5 years; and body mass index, 25.8 Ϯ 3.7 kg/m 2 . ...

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Safety and Adverse Effects Associated With Raloxifene: Multiple Outcomes of Raloxifene Evaluation

Abstract: I

Cited by 141 publications

References 31 publications

Effects of bazedoxifene on bone mineral density, bone turnover, and safety in postmenopausal japanese women with osteoporosis

Effects of bazedoxifene on bone mineral density, bone turnover, and safety in postmenopausal japanese women with osteoporosis

Effects of Tamoxifen Versus Raloxifene on Retinal Capillary Endothelial Cell Proliferation

Procoagulant state after raloxifene therapy in postmenopausal women

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