Raloxifene Hydrochloride

About: Raloxifene Hydrochloride is a research topic. Over the lifetime, 332 publications have been published within this topic receiving 20486 citations.

Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial

Abstract: ContextRaloxifene hydrochloride, a selective estrogen receptor modulator, prevents bone loss in postmenopausal women, but whether it reduces fracture risk in these women is not known.ObjectiveTo determine the effect of raloxifene therapy on risk of vertebral and nonvertebral fractures.DesignThe Multiple Outcomes of Raloxifene Evaluation (MORE) study, a multicenter, randomized, blinded, placebo-controlled trial.Setting and ParticipantsA total of 7705 women aged 31 to 80 years in 25 countries who had been postmenopausal for at least 2 years and who met World Health Organization criteria for having osteoporosis. The study began in 1994 and had up to 36 months of follow-up for primary efficacy measurements and nonserious adverse events and up to 40 months of follow-up for serious adverse events.InterventionsParticipants were randomized to 60 mg/d or 120 mg/d of raloxifene or to identically appearing placebo pills; in addition, all women received supplemental calcium and cholecalciferol.Main Outcome MeasuresIncident vertebral fracture was determined radiographically at baseline and at scheduled 24- and 36-month visits. Nonvertebral fracture was ascertained by interview at 6-month-interim visits. Bone mineral density was determined annually by dual-energy x-ray absorptiometry.ResultsAt 36 months of the evaluable radiographs in 6828 women, 503 (7.4%) had at least 1 new vertebral fracture, including 10.1% of women receiving placebo, 6.6% of those receiving 60 mg/d of raloxifene, and 5.4% of those receiving 120 mg/d of raloxifene. Risk of vertebral fracture was reduced in both study groups receiving raloxifene (for 60-mg/d group: relative risk [RR], 0.7; 95% confidence interval [CI], 0.5-0.8; for 120-mg/d group: RR, 0.5; 95% CI, 0.4-0.7). Frequency of vertebral fracture was reduced both in women who did and did not have prevalent fracture. Risk of nonvertebral fracture for raloxifene vs placebo did not differ significantly (RR, 0.9; 95% CI, 0.8-1.1 for both raloxifene groups combined). Compared with placebo, raloxifene increased bone mineral density in the femoral neck by 2.1% (60 mg) and 2.4% (120 mg) and in the spine by 2.6% (60 mg) and 2.7% (120 mg) P<0.001 for all comparisons). Women receiving raloxifene had increased risk of venous thromboembolus vs placebo (RR, 3.1; 95% CI, 1.5-6.2). Raloxifene did not cause vaginal bleeding or breast pain and was associated with a lower incidence of breast cancer.ConclusionsIn postmenopausal women with osteoporosis, raloxifene increases bone mineral density in the spine and femoral neck and reduces risk of vertebral fracture.

The Effect of Raloxifene on Risk of Breast Cancer in Postmenopausal Women: Results From the MORE Randomized Trial

Abstract: ContextRaloxifene hydrochloride is a selective estrogen receptor modulator that has antiestrogenic effects on breast and endometrial tissue and estrogenic effects on bone, lipid metabolism, and blood clotting.ObjectiveTo determine whether women taking raloxifene have a lower risk of invasive breast cancer.Design and SettingThe Multiple Outcomes of Raloxifene Evaluation (MORE), a multicenter, randomized, double-blind trial, in which women taking raloxifene or placebo were followed up for a median of 40 months (SD, 3 years), from 1994 through 1998, at 180 clinical centers composed of community settings and medical practices in 25 countries, mainly in the United States and Europe.ParticipantsA total of 7705 postmenopausal women, younger than 81 (mean age, 66.5) years, with osteoporosis, defined by the presence of vertebral fractures or a femoral neck or spine T-score of at least 2.5 SDs below the mean for young healthy women. Almost all participants (96%) were white. Women who had a history of breast cancer or who were taking estrogen were excluded.InterventionRaloxifene, 60 mg, 2 tablets daily; or raloxifene, 60 mg, 1 tablet daily and 1 placebo tablet; or 2 placebo tablets.Main Outcome MeasuresNew cases of breast cancer, confirmed by histopathology. Transvaginal ultrasonography was used to assess the endometrial effects of raloxifene in 1781 women. Deep vein thrombosis or pulmonary embolism were determined by chart review.ResultsThirteen cases of breast cancer were confirmed among the 5129 women assigned to raloxifene vs 27 among the 2576 women assigned to placebo (relative risk [RR], 0.24; 95% confidence interval [CI], 0.13-0.44; P<.001). To prevent 1 case of breast cancer, 126 women would need to be treated. Raloxifene decreased the risk of estrogen receptor–positive breast cancer by 90% (RR, 0.10; 95% CI, 0.04-0.24), but not estrogen receptor–negative invasive breast cancer (RR, 0.88; 95% CI, 0.26-3.0). Raloxifene increased the risk of venous thromboembolic disease (RR, 3.1; 95% CI, 1.5-6.2), but did not increase the risk of endometrial cancer (RR, 0.8; 95% CI, 0.2-2.7).ConclusionAmong postmenopausal women with osteoporosis, the risk of invasive breast cancer was decreased by 76% during 3 years of treatment with raloxifene.

Effects of raloxifene on bone mineral density, serum cholesterol concentrations, and uterine endometrium in postmenopausal women.

Abstract: Background Long-term estrogen therapy can reduce the risk of osteoporotic fracture and cardiovascular disease in postmenopausal women. At present, however, these beneficial effects are not separable from undesirable stimulation of breast and endometrial tissues. Methods We studied the effect of raloxifene, a nonsteroidal benzothiophene, on bone mineral density, serum lipid concentrations, and endometrial thickness in 601 postmenopausal women. The women were randomly assigned to receive 30, 60, or 150 mg of raloxifene or placebo daily for 24 months. Results The women receiving each dose of raloxifene had significant increases from base-line values in bone mineral density of the lumbar spine, hip, and total body, whereas those receiving placebo had decreases in bone mineral density. For example, at 24 months, the mean (±SE) difference in the change in bone mineral density between the women receiving 60 mg of raloxifene per day and those receiving placebo was 2.4±0.4 percent for the lumbar spine, 2.4±0.4 per...

Effects of Raloxifene on Serum Lipids and Coagulation Factors in Healthy Postmenopausal Women

Abstract: Context.—Raloxifene is a selective estrogen receptor modulator that has estrogen-agonistic effects on bone and estrogen-antagonistic effects on breast and uterus.Objective.—To identify the effects of raloxifene on markers of cardiovascular risk in postmenopausal women, and to compare them with those induced by hormone replacement therapy (HRT).Design.—Double-blind, randomized, parallel trial.Setting.—Eight sites in the United States.Participants.—390 healthy postmenopausal women recruited by advertisement.Intervention.—Participants were randomized to receive 1 of 4 treatments: raloxifene, 60 mg/d; raloxifene, 120 mg/d; HRT (conjugated equine estrogen, 0.625 mg/d, and medroxyprogesterone acetate, 2.5 mg/d); or placebo.Main Outcome Measures.—Change and percent change from baseline of lipid levels and coagulation parameters after 3 months and 6 months of treatment.Results.—At the last visit completed, compared with placebo, both dosages of raloxifene significantly lowered low-density lipoprotein cholesterol (LDL-C) by 12% (P<.001), similar to the 14% reduction with HRT (P<.001). Both dosages of raloxifene significantly lowered lipoprotein(a) by 7% to 8% (P<.001), less than the 19% decrease with HRT (P<.001). Raloxifene increased high-density lipoprotein-2 cholesterol (HDL2-C) by 15% to 17% (P<.05), less than the 33% increase with HRT (P<.001). Raloxifene did not significantly change high-density lipoprotein cholesterol (HDL-C), triglycerides, or plasminogen activator inhibitor-1 (PAI-1); whereas HRT increased HDL-C by 11% and triglycerides by 20%, and decreased PAI-1 by 29% (for all, P< .001). Raloxifene significantly lowered fibrinogen by 12% to 14% (P<.001), unlike HRT, which had no effect. Neither treatment changed fibrinopeptide A or prothrombin fragment 1 and 2.Conclusions.—Raloxifene favorably alters biochemical markers of cardiovascular risk by decreasing LDL-C, fibrinogen, and lipoprotein(a), and by increasing HDL2-C without raising triglycerides. In contrast to HRT, raloxifene had no effect on HDL-C and PAI-1, and a lesser effect on HDL2-C and lipoprotein(a). Further clinical trials are necessary to determine whether these favorable biochemical effects are associated with protection against cardiovascular disease.

Raloxifene (LY139481 HCI) Prevents Bone Loss and Reduces Serum Cholesterol without Causing Uterine Hypertrophy in Ovariectomized Rats

Abstract: There is a medical need for an agent with the positive effects of estrogen on bone and the cardiovascular system, but without the negative effects on reproductive tissue. Raloxifene (LY139481 HCI) is a benzothiophene derivative that binds to the estrogen receptor and inhibits the effects of estrogen on the uterus. In an ovariectomized (OVX) rat model we investigated the effects of raloxifene on bone loss (induced by estrogen deficiency), serum lipids, and uterine tissue. After oral administration of raloxifene for 5 wk (0.1-10 mg/kg per d) to OVX rats, bone mineral density in the distal femur and proximal tibia was significantly greater than that observed in OVX controls (ED50 of 0.03-0.3 mg/kg). Serum cholesterol was lower in the raloxifene-treated animals, which had a minimal effective dose of 0.1 mg/kg and an approximate oral ED50 of 0.2 mg/kg. The effects of raloxifene on bone and serum cholesterol were comparable to those of a 0.1-mg/kg per d oral dose of ethynyl estradiol. Raloxifene diverged dramatically from estrogen in its lack of significant estrogenic effects on uterine tissue. Ethynyl estradiol produced a marked elevation in a number of uterine histologic parameters (e.g., epithelial cell height, stromal eosinophilia). These data suggest that raloxifene has promise as an agent with beneficial bone and cardiovascular effects in the absence of significant uterine effects.