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PubMed2001

Lack of substantial effects of raloxifene on thyroxine-binding globulin in postmenopausal women: dependency on thyroid status.

Long-term estrogen therapy can modify thyroid hormone kinetics by increasing serum concentration of thyroxine-binding globulin (TBG). Raloxifene is a recently developed selective estrogen receptor modulator (SERM) for the treatment of osteoporosis, which possesses estrogenic and antiestrogenic properties. In a prospective and randomized study, we investigated the effects of raloxifene on TBG levels and on the serum concentrations of free thyroxine (FT4), thyroxine (T4), triiodothyronine (T3), and thyrotropin (TSH) in controls and in patients receiving TSH-suppressive doses of levothyroxine (LT4). Twenty-nine postmenopausal osteopenic (n = 14) and osteoporotic (n = 15) women were investigated over a period of 6 months. Group 1 (n = 15) included control patients and group 2 (n = 14) patients receiving TSH-suppressive dose of LT4. All patients were treated with raloxifene hydrochloride, 60 mg/d, for a period of 6 months. Serum basal TBG values were found higher in Group 1 compared to Group 2 (26.2 2 microg/mL vs. 21.4 2.1 microg/ml; p < 0.01). The TBG levels raised slightly in group 1 from 26.2 2 microg/mL to 28.6 3.1 microg/mL; p < 0.05 (in group 2 from 21.4 2.1 microg/mL to 22.2 2.3 microg/mL, not significant) after 3 months of treatment and failed to show any further significant change until the end of the study. Serum concentrations of T4, FT4, T3, and TSH levels changed insignificantly in both groups up to the completion of the study. Moreover, patients remained clinically euthyroid. Our findings may provide evidence that TBG levels, and consequently, thyroid function are not substantially affected by treatment with raloxifene. Additionally, TBG levels may also be influenced by small variations of thyroid function as subclinical hyperthyroidism.

Aged↗
PubMed2005

Effect of raloxifene on serum triglycerides in women with a history of hypertriglyceridemia while on oral estrogen therapy.

OBJECTIVE: Raloxifene hydrochloride is a selective estrogen receptor modulator that to date has not been shown to cause hypertriglyceridemia in normal, diabetic, or hypertriglyceridemic women. This study was designed to assess the effect of raloxifene on serum triglycerides in postmenopausal women who have a history of increased hypertriglyceridemia with oral estrogen therapy. RESEARCH DESIGN AND METHODS: This was a single-center, uncontrolled, open-label study investigating the effects of 8 weeks of raloxifene (60 mg/day) therapy on plasma lipids. The study subjects were 12 postmenopausal women, ages 49-73 years, with a documented history of oral estrogen-induced hypertriglyceridemia (serum triglycerides > or =3.39 mmol/l [> or =300 mg/dl]). RESULTS: At week 2 of the study, three (25%) of the subjects withdrew from the trial because they developed marked hypertriglyceridemia (>or =11.3 mmol/l [> or =1,000 mg/dl]) during raloxifene therapy. These three women had higher baseline triglyceride and glucose levels, were not being treated with lipid-lowering agents, and were more likely to have diabetes than the other study subjects. The remaining nine patients (75%) completed the 8-week trial and experienced a nonsignificant increase in mean triglyceride levels from baseline to end point. Raloxifene treatment also resulted in a significant 16% decrease in hepatic lipase activity and a 26% increase in HDL(2) levels (P = 0.013 and 0.03, respectively). CONCLUSIONS: Patients with a previous history of hypertriglyceridemia on oral estrogen therapy should have serum triglyceride levels monitored closely after beginning raloxifene therapy and may even require fibrate therapy before beginning raloxifene.

Aged↗
PubMed2005

[Raloxifene (Evista) in the treatment of postmenopausal osteoporosis--the profile of the patient].

Osteoporosis, breast cancer and cardiovascular diseases are major health problems among postmenopausal women. Several pharmacologic options for treatment of osteoporosis are available, including hormone replacement therapy (HRT), bisphosphonates, calcitonin and selective estrogen receptor modulators. However, longterm HRT is associated with unwanted side effects such as vaginal bleeding and breast cancer and bisphosphonates, besides bone, have no other benefits. Therefore, raloxifene, the first of the second-generation of SERMs represents a significant improvement in the treatment of postmenopausal women. It could have either estrogen agonist (bone) or antagonist (breast) activity according to the type of estrogen-responsive tissue. Raloxifene prevents bone loss, reduces the number of vertebral fractures in women with and without prevalent vertebral fractures, induces reduction of estrogen-receptor positive invasive breast cancer and has potential beneficial effect on cardiovascular diseases in women with high risk. CORE study, that was recently published, confirmed previously observed reduction of invasive breast cancer in women treated with raloxifene (MORE study), while the data on skeletal effects after 8-years treatment with raloxifene will be published in the near future. Further studies (RUTH, STAR) will provide additional information on efficacy and safety of raloxifene.

Female↗
PubMed2002

[Tamoxifen and breast cancer].

Tamoxifen is a selective estrogen receptor modulator (SERM) with pro- and anti-estrogenic properties. Currently it is the most widely used agent for first line treatment against hormone sensitive metastatic breast cancer and the only approved hormonal agent for adjuvant treatment of organ confined breast cancer. Furthermore, its uses have been extended for the treatment of intraductal breast carcinoma patients. In such settings the most worrisome side effect of tamoxifen is its ability to increase the rates of uterine cancers. It has been claimed that most of these cancers are found at an early stage because of vaginal bleeding. Moreover, it has been shown that for most women transvaginal ultrasound is an ineffective screening method for the early detection of uterine carcinomas. It is important, however, to notice that long term tamoxifen treatment can cause metastatic uterine cancer--not only carcinomas but also sarcomas (mainly malignant mixed mesodermal tumors. It should be noted that, at least for the special population of BRCA mutation carriers, transvaginal ultrasound can increase our ability for the earlier discovery of ovarian cancer. Thus, we believe that there is still a place for the use of transvaginal ultrasound in special populations. This is specifically for long term tamoxifen users (more than the usually recommended five years), women with a higher chance of having uterine carcinomas (namely very high body weight, strong family history) and women with a high index of suspicion as carriers of a BRCA mutation. Until new second generation SERMs and aromatase inhibitors are shown to possess better anti-cancer abilities than tamoxifen, this drug will remain in wide use, however, we must not overlook its possible rare side effects.

Antineoplastic Agents, Hormonal↗
PubMed2002

Effects of raloxifene after tamoxifen on breast and endometrial tumor growth in athymic mice.

BACKGROUND: In patients with early-stage breast cancer, 5 years of treatment with the selective estrogen receptor modulator (SERM) tamoxifen reduces breast cancer recurrence and mortality, whereas more than 5 years of tamoxifen does not further reduce breast cancer recurrence and doubles the risk of endometrial cancer. We evaluated the effects on tumor growth of raloxifene, another SERM, after tamoxifen treatment in mouse models of breast and endometrial cancers. METHODS: Athymic, ovariectomized mice were bitransplanted with tumors derived from human breast cancer and endometrial cancer cells that either were tamoxifen-naive or had been exposed to tamoxifen for short (6 months) or long (>5 years) terms. The effects of raloxifene (two dose levels) and tamoxifen on tumor growth in the presence and absence of low-dose estrogen were evaluated. All statistical tests were two-sided. RESULTS: Raloxifene was less effective than tamoxifen in blocking the stimulatory effects of low-dose estrogen on the growth of tamoxifen-naive breast (P<.001) and endometrial (P =.001) tumors. Raloxifene and tamoxifen had similar inhibitory effects on the growth of short-term tamoxifen-exposed breast tumors. Raloxifene and tamoxifen had similar stimulatory effects on the growth of breast and endometrial tumors that had been exposed to at least 5 years of tamoxifen. However, neither drug blocked the stimulatory effects of estrogen on the growth of these tumors. Raloxifene was less effective than tamoxifen (P<.001) in blocking the stimulatory effects of estrogen on endometrial tumors that had been exposed to tamoxifen in the past. CONCLUSIONS: Raloxifene and tamoxifen had similar effects on these mouse models of tamoxifen-naive and tamoxifen-resistant breast and endometrial cancer. Treatment with raloxifene following 5 years of adjuvant tamoxifen may not further decrease breast cancer recurrence and may increase endometrial cancer incidence.

Animals↗
PubMed2002

Effect of 1 year of discontinuation of raloxifene or estrogen therapy on bone mineral density after 5 years of treatment in healthy postmenopausal women.

The beneficial effects of hormone replacement therapy (HRT), selective estrogen receptor modulators (SERMs), or bisphosphonates in the prevention and treatment of osteoporosis in postmenopausal women have been well established. However, little is known about the effects of discontinuation of treatment on bone mineral density. We investigated the effect of 1 year of discontinuation of the SERM raloxifene (Ral; 60 mg and 150 mg), conjugated equine estrogen (CEE; 0.625 mg), and placebo after 5 years of treatment in a double-blind, randomized study. Thirty-eight of 59 healthy and hysterectomized postmenopausal women (mean age 55 years) completed the treatment and 1 year follow-up period. Lumbar spine and femoral neck bone mineral density (BMD) were performed with dual-energy X-ray absorptiometry, before, during, and at the end of treatment, as well as after 1 year of discontinuation of therapy. One year of discontinuation significantly reduced the mean lumbar spine BMD in the raloxifene- and estrogen-treated women (p < 0.05), whereas mean femoral neck BMD was reduced significantly only in women treated with 60 mg Ral (p < 0.05). The mean percentage change (+/-SD) in lumbar spine BMD was: CEE, -6.2% (+/-3.7%); Ral 60 mg, -2.4% (+/-2.4%); Ral 150 mg, -2.6% (+/-3.1%); and placebo, -1.6% (+/-4.3%). Our results show that 5 years of treatment with either Ral or CEE did not protect against bone loss after 1 year of withdrawal of therapy, and that the rate of bone loss was not significantly different from that of placebo-treated women.

Bone Density↗
PubMed2002

SERMs: current status and future trends.

Selective estrogen receptor modulators, or SERMs, are a class of compounds that can act as estrogen receptor (ER) agonists in some tissues while acting as ER antagonists in others. SERMs are being evaluated and used to treat and prevent such diseases as breast cancer, osteoporosis, and cardiovascular disease. Currently, three primary SERMs are used clinically, which include tamoxifen, toremifene (triphenylethylenes), and raloxifene (a benzothiophene). Tamoxifen and toremifene have beneficial effects on bone and serum lipids, and are currently used to treat breast cancer. Both have stimulatory effects on the uterus. Raloxifene, indicated for the treatment and prevention of osteoporosis, also has beneficial effects on bone and serum lipids, but does not stimulate the uterus. All three are associated with venous thromboembolism and hot flashes. New SERMs to treat and prevent breast cancer, osteoporosis, and cardiovascular disease are undergoing clinical development, including idoxifene, droloxifene, ospemifene, lasofoxifene, arzoxifene, and MDL 103,323.

Animals↗
PubMed2003

An observational study of severe hypertriglyceridemia, hypertriglyceridemic acute pancreatitis, and failure of triglyceride-lowering therapy when estrogens are given to women with and without familial hypertriglyceridemia.

BACKGROUND: We assessed severe hypertriglyceridemia, hypertriglyceridemic acute pancreatitis, and failure of triglyceride-lowering therapy when estrogens were given to 56 women with and without familial hypertriglyceridemia. The 56 women had been consecutively referred to our center over a 3-year period because of triglycerides >400 mg/dl despite diet-drug treatment and/or a history of hypertriglyceridemic acute pancreatitis (AP). Of the 56 women, 17 had received estrogen replacement therapy (ERT), hormone replacement (HRT, n=6), or selective estrogen receptor modulators (SERM, n=1). METHODS: After study at entry, in 56 women (median age, 52 years), 36 with familial hypertriglyceridemia, to lower triglycerides, estrogens and SERMs (hormone treatment, HT) were stopped; a very low fat diet (<15% of calories), gemfibrozil (1.2-1.5 mg/day), and omega-3-fatty acid (4-12 g/day) were started, with restudy 2-4 weeks later. RESULTS: Of the 56 women, 24 (43%) were taking HT at entry, with median fasting triglycerides 1270 mg/dl in the HT group and 1087 mg/dl in the no-HT group. Seventeen women (30%) had a history of AP, nine of whom (53%) were/had been on HT at the development of AP. Significant positive correlates of triglycerides at entry in a stepwise regression model were hemoglobin A(1C) (partial r(2)=10.7%, p<0.05) and an interaction between estrogen use and familial hypertriglyceridemia (partial r(2)=15%, p=0.017). After 2-4 weeks on therapy, median triglycerides in the previous-HT group fell from 1270 to 284 mg/dl (p<0.0001) and in the no-HT group from 1087 to 326 mg/dl (p<0.0001). CONCLUSIONS: Before starting HT, to avoid HT induced hypertriglyceridemic AP and exacerbation of overt or covert familial hypertriglyceridemia, triglycerides must be measured. HT is contraindicated in women with preexisting hypertriglyceridemia (triglycerides> or =500 mg/dl). Triglyceride-lowering diets and drugs often fail in the presence of HT and/or poorly controlled diabetes mellitus, but commonly succeed when HT is stopped and diabetes mellitus is tightly controlled.

Adult↗
PubMedDate not supplied

Validation of rat endometriosis model by using raloxifene as a positive control for the evaluation of novel SERM compounds.

Approximately 10% of women of reproductive age suffer from endometriosis, a potentially painful disease process and important cause of female infertility. Raloxifene, a commercially available SERM (selective estrogen receptor modulator) compound, used for the treatment of postmenopausal osteoporosis, has preclinically demonstrated its estrogen antagonist effect on uterine tissue in rats. There is potential that SERM compounds may become a viable treatment option for human endometriosis, although more investigation is needed. In this study, raloxifene was administered at various doses to determine the efficacy and an appropriate dose level for use as a positive control in a rat model of endometriosis. Prior to dose administration, all rats underwent a bilateral ovariectomy, autologous transplantation of uterine tissue onto the peritoneal surface of the abdominal wall, and implantation of a subcutaneous estrogen pellet (E2). Two separate postsurgical experiments were performed. In experiment 1, following a 4-wk recovery, the rats bearing implants were assigned to three groups: (1) removal of the E2 pellet and dosing vehicle only (n = 7); (2) E2 and vehicle (n = 6); and (3) E2 and raloxifene at 10.0 mg/kg (n = 6). In experiment 2, also following a 4-week recovery, the rats bearing implants were assigned to five groups (n = 8/group): (1) E2 and vehicle only; (2) E2 and raloxifene, 0.3 mg/kg/d; (3) E2 and raloxifene, 1.0 mg/kg/d; (4) E2 and raloxifene, 3.0 mg/kg/d; (5) E2 and raloxifene, 10.0 mg/kg/d. All rats were dosed orally BID for 14 d. At the end of the study, the implanted endometrium was remeasured and compared to the pretreatment measurement. The results from both studies demonstrated that Raloxifene at only one dose (10.0 mg/kg) displayed significant implant regression (p < .05). Subsequently, our rat endometriosis experimental model consistently uses the exogenous E2 pellet and raloxifene at 10 mg/kg, BID, as a positive control to help screen and compare novel SERM compounds.

Animals↗
PubMed2005

Hypolipidemic action of the SERM acolbifene is associated with decreased liver MTP and increased SR-BI and LDL receptors.

This study aimed to identify the mechanisms of the hypolipidemic action of the selective estrogen receptor modulator (SERM) acolbifene (ACOL). Four weeks of treatment with ACOL reduced fasting and postprandial plasma triglycerides (TGs), an effect associated with lower VLDL-TG secretion rate (-25%), and decreased mRNA of microsomal triglyceride transfer protein (MTP; -29%). ACOL increased liver TG concentration (+100%) and amplified the feeding-induced increase in the master lipogenic regulators sterol-regulatory element binding protein-1a (SREBP-1a) and SREBP-1c. ACOL decreased total, HDL, and non-HDL cholesterol (CHOL) by 50%. SREBP-2 mRNA and HMG-CoA reductase activity were minimally affected by ACOL. However, in the fasted state, liver concentration of scavenger receptor class B type I (SR-BI) protein, but not mRNA, was 3-fold higher in ACOL-treated than in control animals and correlated with plasma HDL-CHOL levels (r = 0.80, P < 0.002). Liver LDL receptor (LDLR) protein, but not mRNA, was increased 2-fold by ACOL, independently of the nutritional status. This study demonstrates that ACOL possesses the unique ability among SERMs to reduce VLDL-TG secretion, likely by reducing MTP expression, and strongly suggests that the robust hypocholesterolemic action of ACOL is related to increased removal of CHOL from the circulation as a consequence of enhanced liver SR-BI and LDLR abundance.

Animals↗
PubMed2003

Raloxifene lowers IGF-I levels in acromegalic women.

BACKGROUND: IGF-I suppression in acromegaly obtained by tamoxifen, a selective estrogen receptor modulator (SERM), prompted us to evaluate the effects of the administration of a newer SERM, raloxifene (RAL), devoid of estrogenic activity at uterine level, on GH/IGF-I levels in patients with this disease. PATIENTS: Thirteen post-menopausal acromegalic women (aged 55-84 years) with active acromegaly entered a prospective open pilot study of RAL treatment at 60 mg/day. Nine of the patients, who were resistant to somatostatin analog and dopamine agonist treatment, were not undertaking therapy; the other four, who were partially sensitive to medical treatment, maintained treatment at the maximally effective dosages throughout the study. RESULTS: IGF-I levels fell significantly from 444 (median, interquartile 393-590) microg/l to 300 (216-608) microg/l (P=0.0192) after 1 month of RAL administration and this fall remained stable up to the final evaluation at 5+/-1 months from the start of RAL treatment (260 (187-410) microg/l). An IGF-I decrease greater than 30% of basal values was observed in 10 patients (mainly in patients with IGF-I levels lower than 600 microg/l) and normal values were reached in seven (54%). GH levels did not change (basal 6 (4.1-8) microg/l, final 5.5 (3.2-7.4) microg/l). The clinical picture improved in patients sensitive to RAL. RAL withdrawal was followed by the return of IGF-I levels to pretreatment values within 8 weeks in all patients. CONCLUSIONS: RAL decreases IGF-I levels in most acromegalic women with mild or intermediate disease (i.e. with values lower than 600 microg/l) and normalizes it in many. A prospective randomized study in patients resistant or partially sensitive to other medical treatments is warranted.

Acromegaly↗
PubMed2004

Comparative vascular effects of hormone replacement therapy and raloxifene in women at increased cardiovascular risk.

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.

Aged↗
PubMed2001

Design and methods of the Raloxifene Use for The Heart (RUTH) study.

Raloxifene is a selective estrogen receptor modulator that lowers total and low-density lipoprotein (LDL) cholesterol, reduces the risk of vertebral fracture, and is associated with a reduced incidence of invasive breast cancer in postmenopausal women with osteoporosis. The Raloxifene Use for The Heart (RUTH) trial is designed to determine whether raloxifene 60 mg/day compared with placebo: (1) lowers the risk of the coronary events (coronary death, nonfatal myocardial infarction [MI], or hospitalized acute coronary syndromes other than MI); and (2) reduces the risk of invasive breast cancer in women at risk for a major coronary event. RUTH is a double-blind, placebo-controlled, randomized clinical trial of 10,101 postmenopausal women aged > or =55 years from 26 countries. Women are eligible for randomization if they are postmenopausal and have documented coronary heart disease (CHD), peripheral arterial disease, or multiple risk factors for CHD. Use of estrogen within the previous 6 months is an exclusion factor. The study will be terminated after a minimum of 1,670 participants experience a primary coronary end point. Secondary end points include cardiovascular death, myocardial revascularization, noncoronary arterial revascularization, stroke, all-cause hospitalization, all-cause mortality, all breast cancers, clinical fractures, and venous thromboembolic events, in addition to the individual components of the composite primary coronary end point. RUTH will provide important information about the risk-benefit ratio of raloxifene in preventing acute coronary events and invasive breast cancer, as well as information about the natural history of CHD in women at risk of major coronary events.

Angina, Unstable↗
PubMed2002

The hemorheological effects of raloxifene in postmenopausal women with osteoporosis. Results of a 3-year placebo-controlled clinical trial.

Raloxifene, the prototype of the selective estrogen receptor modulators, has been associated with an increased risk of venous thromboembolism. As hemorheological factors may be involved in thrombus formation this placebo-controlled study investigated whether raloxifene was associated with changes in determinants of blood viscosity. Fifty-seven post-menopausal women were randomly assigned to receive placebo, raloxifene 60 mg/day, or raloxifene 120 mg/day for 36 months. Venous blood samples were collected at baseline and at 12-monthly intervals and used to measure hematocrit, whole blood and plasma viscosity and plasma fibrinogen concentration. Time- and treatment-related changes in the grouped and pooled data was analysed using ANOVA with repeated measures and correlation matrices. The mean values of all the hemorheological indices showed small inconsistent changes within the normal reference range over the 36-month period of the study. There was a small but significant decrease over time in high shear rate blood viscosity and plasma viscosity in raloxifene-treated subjects compared to those receiving placebo (p<0.05). Correlation analyses showed the anticipated relationships between blood viscosity and hematocrit and plasma viscosity levels and also between plasma viscosity and plasma fibrinogen concentration. No subject developed a thromboembolic vascular event during the study. These results show that compared with placebo treated-subjects, long-term raloxifene treatment in post-menopausal women, at a dose of either 60 or 120 mg daily, was not associated with adverse changes in hemorheological factors that may contribute to venous thromboembolism.

Aged↗
PubMed2005

Raloxifene exposure enhances brain activation during memory performance in healthy elderly males; its possible relevance to behavior.

Raloxifene is a selective estrogen receptor modulator (SERM) that is prescribed in females only, but its use in male subjects is increasingly considered. With a growing number of patients having potential benefit from raloxifene, the need for an assessment of its effects on brain function is growing. Effects of estrogens on brain function are very subtle and difficult to detect by neuropsychological assessment. Functional imaging techniques, however, have been relatively successful in detecting such changes. This study used functional magnetic resonance imaging (fMRI) to examine effects of raloxifene treatment on memory function. Healthy elderly males (n = 28; mean age 63.6 years, SD 2.4) were scanned during performance on a face encoding paradigm. Scans were made at baseline and after 3 months of treatment with either raloxifene (n = 14) or placebo (n = 14). Treatment effects were analyzed using mixed-effects statistical analysis (FSL). Activation during task performance involved bilateral parietal and prefrontal areas, anterior cingulate gyrus, and inferior prefrontal, occipital, and mediotemporal areas bilaterally. When compared to placebo, raloxifene treatment significantly enhanced activation in these structures (Z > 3.1), except for mediotemporal areas. Task performance accuracy diminished in the placebo group (P = 0.02), but remained constant in the raloxifene group (P = 0.60). In conclusion, raloxifene treatment enhanced brain activation in areas spanning a number of different cognitive domains, suggesting an effect on cortical arousal. Such effects may translate into small effects on behavior, including effects on attention and working memory performance, executive functions, verbal skills, and episodic memory. Further neuropsychological assessment is necessary to test the validity of these predictions.

Aged↗
PubMed2003

The effects of raloxifene and simvastatin on plasma lipids and endothelium.

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.

Aged↗
PubMed2001

Digitized mammography: a clinical trial of postmenopausal women randomly assigned to receive raloxifene, estrogen, or placebo.

BACKGROUND: High mammographic density is associated with increased breast cancer risk. Previous studies have shown that estrogens increase breast density on mammograms, but the effect on mammographic density of selective estrogen receptor modulators, such as raloxifene, is unknown. We assessed changes in mammographic density among women receiving placebo, raloxifene, or conjugated equine estrogens in an osteoporosis prevention trial. METHODS: In a 5-year multicenter, double-blind, randomized, placebo-controlled osteoporosis prevention trial, healthy postmenopausal women who had undergone hysterectomy less than 15 years before the study and had no history of breast cancer received placebo, raloxifene (at one of two doses), or conjugated estrogens (ERT). Women from English-speaking investigative sites who had baseline and 2-year craniocaudal mammograms with comparable positioning (n = 168) were eligible for this analysis. Changes in mammographic density were determined by digital scanning and computer-assisted segmentation of mammograms and were analyzed with the use of analysis of variance. All statistical tests were two-sided. RESULTS: Among the four treatment groups after 2 years on study, the mean breast density (craniocaudal view) was statistically significantly greater in the ERT group than it was in the other three groups (P<0.01 for all three comparisons). Within treatment groups, the mean breast density from baseline to 2 years decreased statistically significantly in women receiving the placebo or either the higher or lower raloxifene dose (P = 0.003, P = 0.002, and P<0.001, respectively) and showed a nonstatistically significant increase in women receiving ERT. CONCLUSIONS: In an osteoporosis prevention trial, raloxifene did not increase breast density after 2 years of treatment. Raloxifene administration should not interfere with, and could even enhance, mammographic detection of new breast cancers.

Breast↗
PubMed2000

Future possibilities in the prevention of breast cancer: role of genetic variation in breast cancer prevention.

Risk factors for breast cancer are related to endogenous hormones and reproductive events. As such, traditional cancer prevention strategies are not easily applicable. Tamoxifen and other selective estrogen receptor modulators (SERMs) offer a new preventive strategy for some high-risk women, but have not yet been shown to be efficacious for all women. New tools to identify high-risk women are needed. One such tool is the development of a multigenic model of breast cancer susceptibility that can be used to screen women in order to identify those who carry a combination of alleles that puts them at significantly increased risk.

Adult↗