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PubMed2000

Estrogen receptor pathways to AP-1.

Estrogen receptor (ER) binds to estrogen response elements in target genes and recruits a coactivator complex of CBP-pl60 that mediates stimulation of transcription. ER also activates transcription at AP-1 sites that bind the Jun/Fos transcription factors, but not ER. We review the evidence regarding mechanisms whereby ER increases the activity of Jun/Fos and propose two pathways of ER action depending on the ER (alpha or beta) and on the ligand. We propose that estrogen-ERalpha complexes use their activation functions (AF-1 and AF-2) to bind to the p 160 component of the coactivator complex recruited by Jun/Fos and trigger the coactivator to a higher state of activity. We propose that selective estrogen receptor modulator (SERM) complexes with ERbeta and with truncated ERalpha derivatives use their DNA binding domain to titrate histone deacetylase (HDAC)-repressor complexes away from the Jun/Fos coactivator complex, thereby allowing unfettered activity of the coactivators. Finally, we consider the possible physiological significance of ER action at AP-1 sites.

Animals↗
PubMed2006

A single-dose pharmacokinetic study of lasofoxifene in healthy volunteers and subjects with mild and moderate hepatic impairment.

Lasofoxifene, a selective estrogen receptor modulator for osteoporosis management, is metabolized primarily by hepatic oxidation and conjugation. This study compared the pharmacokinetics of 0.25 mg lasofoxifene in subjects with mild (Child-Pugh grade A, n = 6) or moderate (Child-Pugh grade B, n = 6) hepatic impairment and healthy volunteers (n = 6). Analysis of variance was used to calculate 90% confidence intervals for the ratios (impaired/healthy) of least squares mean log maximum plasma concentration (C(max)) and area under the curve (AUC) values. Lasofoxifene pharmacokinetics was similar between healthy and mild hepatic impairment subjects: ratios of C(max) and AUC from 0 to infinity (AUC([0-infinity])) were 101% (75.0-138) and 95.5% (77.9-117), respectively. In subjects with moderate hepatic impairment, ratios of C(max) and AUC([0-infinity]) were 121% (89.6-165) and 138% (112-169), respectively; mean terminal half-life was 252 hr compared to 193 hr in healthy subjects. Dose adjustment should not be required for subjects with mild to moderate hepatic impairment.

Administration, Oral↗
PubMed2005

HPLC analysis of raloxifene hydrochloride and its application to drug quality control studies.

Raloxifene hydrochloride is a selective estrogen receptor modulator and is currently being used for prevention of osteoporosis in postmenopausal women. In this article, a high performance liquid chromatography (HPLC) method for detection of raloxifene hydrochloride was developed and validated using an ultraviolet (UV) and coulometric detectors. Limit of quantification (LOQ) was 0.336 and 0.610 mg L(-1) for coulometric and ultraviolet detectors, respectively. Acceptable accuracy (93.1-100.3%) as well as intra- and inter-day precision (CV<or=2.38% and CV<or=7.93%, respectively) was demonstrated in the range of 0.5-10 mg L(-1) for both detectors. The presented method was applied without any interference of excipients to the determination of raloxifene hydrochloride content in tablets and to the in vitro dissolution studies. The proposed method could be used for routine quality control. Moreover, due to its low LOQ, excellent accuracy, precision and selectivity, the coulometric detection could be applied to in vitro metabolism experiments such as microsome or hepatocyte preparations and for studies of transport of raloxifene hydrochloride across biological membranes.

Chromatography, High Pressure Liquid↗
PubMed2004

Effects of a long-term treatment with raloxifene on insulin sensitivity in postmenopausal women.

AIMS/HYPOTHESIS: Our aim was to investigate the effect of long-term administration of raloxifene, a selective estrogen receptor modulator, on insulin sensitivity, glucose tolerance and plasma lipid concentrations in a group of postmenopausal women. METHODS: A total of 24 women with postmenopausal osteoporosis were consecutively enrolled and randomly assigned to take raloxifene, 60 mg/day for 12 months or placebo. At baseline and after 6 and 12 months, in each subject insulin sensitivity (M-index) was assessed by means of an euglycaemic hyperinsulinaemic clamp. Plasma concentrations of total cholesterol, triglycerides and HDL-cholesterol were also measured and glucose tolerance was evaluated. RESULTS: In the raloxifene-treated group, the M index decreased after 6 and 12 months with respect to the placebo group (-21%, p=0.042 and -23%, p=0.018, respectively). Neither fasting plasma glucose nor glucose tolerance changed in the raloxifene-treated group, compared to the placebo group. Low density lipoprotein cholesterol concentrations decreased at 12 months (-13%, p=0.047). CONCLUSION/INTERPRETATION: A long-term treatment with raloxifene in osteoporotic, otherwise healthy post-menopausal women can reduce insulin sensitivity without affecting glucose tolerance.

Blood Glucose↗
PubMed2006

Clinical pharmacology of multiple doses of lasofoxifene in postmenopausal women.

Lasofoxifene, a next-generation selective estrogen receptor modulator, is undergoing phase 3 clinical development for osteoporosis. This study evaluated daily lasofoxifene for 14 days in healthy postmenopausal women. A loading dose of 5 times the daily dose was followed by daily doses of 0.01 mg (n = 8), 0.03 mg (n =8), 0.1 mg(n = 16), 0.3 mg (n =9), 1 mg (n = 8), or placebo (n = 16). Samples were collected for pharmacokinetic and pharmacodynamic assessments. Lasofoxifene was well tolerated; study drug-associated adverse events were mild and unrelated to dose. There was a predictable increase in plasma concentrations of lasofoxifene with dose. Pharmacokinetic parameters included mean half-life of 165 hours, mean area under the plasma concentration-time curve from time 0 to 24 hours ranging from 1.67 ng x h/mL to 137 ng x h/mL, and mean maximum observed plasma concentration ranging from 0.09 ng/mL to 6.43 ng/mL. Lasofoxifene partially suppressed luteinizing hormone, follicle-stimulating hormone, low-density lipoprotein, and N-telopeptide.

Administration, Oral↗
PubMed2005

Vascular effects of aromatase inhibitors: data from clinical trials.

Aromatase inhibitors (AIs) are becoming the endocrine treatment of first choice for postmenopausal women with hormone receptor-positive breast cancer and are under investigation for use in breast cancer prevention. AIs reduce circulating estrogen to barely detectable concentrations. It is possible that such a low concentration will be deleterious to the vascular system since estrogen receptors are known to be in the cell walls of blood vessels and estrogen is thought to be important in maintaining blood vessel integrity. Because most women who present with primary breast cancer are cured by surgery and systemic therapy and the major cause of female death is vascular disease, it is particularly important to investigate the vascular side effects of AIs in current breast cancer adjuvant and prevention trials. In order to set the vascular toxicities of AIs reported in the current adjuvant trials into context, here we compare them with the toxicities seen during treatment with hormone replacement therapy (HRT) and selective estrogen receptor modulators (SERMs). Clinical trial evidence indicates that HRT increases risk of coronary heart disease (CHD) whereas SERMs and AIs (to date) appear to be neutral. Cerebrovascular disease and venous thromboembotic events are increased by HRT and SERMs but appear to be unaffected by treatment with AIs. Cognitive function is also considered here since it may also have a vascular component and is potentially a serious potential side effect/benefit of AIs. Recent studies indicate that HRT has a small detrimental effect on cognitive function and is associated with a doubling of the incidence of dementia. A comprehensive study of the SERM, raloxifene, on cognitive function showed no significant effect. There are no definitive reported studies investigating tamoxifen and none for AIs on cognitive function, although there is one in progress in the context of the IBIS II prevention trial which compares anastrozole to placebo in women at high risk. At present concerns about deleterious vascular side effects are confined to HRT and SERMs. However, we have few long-term data using AIs for the treatment and prevention of breast cancer.

Antineoplastic Agents, Hormonal↗
PubMed2004

Antiresorptive treatment of postmenopausal osteoporosis: review of randomized clinical studies and rationale for the Evista alendronate comparison (EVA) trial.

Standard pharmacological antiresorptive therapy for the prevention and/or treatment of postmenopausal osteoporosis now consists of four categories of drugs: estrogens, a selective estrogen receptor modulator (SERM), bisphosponates, and calcitonin. All of these drugs have been studied in randomized controlled trials, but meaningful comparisons of the efficacy of drugs have been difficult due to differences in baseline risks for fracture and differences in study design, including calcium and vitamin D supplementation, definition of fracture, and discontinuation rates. The current paper reviews results from pivotal studies of antiresorptive therapies with fracture as a primary endpoint, as well as head-to-head trials comparing these therapies using surrogate markers of fracture risk, and introduces the first head-to-head trial with fracture as a primary endpoint. The Evista Alendronate Comparison (EVA) trial, a multi-center, double-blind, double-dummy, randomized trial with two active treatment arms is currently underway to compare directly the osteoporotic fracture risk reduction efficacy of raloxifene and alendronate in postmenopausal women with osteoporosis as defined by bone mineral density. The results from this trial will permit more informed judgment by practitioners and provider groups concerning the relative clinical utility of these two drugs.

Alendronate↗
PubMed2006

Antiestrogens and the formation of DNA damage in rats: a comparison.

Tamoxifen (TAM) has been used as an agent for the treatment and prevention of breast cancer. However, long-term treatment of TAM in women increases the risk of developing endometrial cancer. The secondary cancer may be due to the genotoxicity of TAM. To find safer alternatives, four selective estrogen receptor modulators (SERMs), 4-hydroxytamoxifen (4-OHTAM), toremifene (TOR), raloxifene (RAL), and ICI 182,780, were administered to rats with an equimolar dose of TAM [54 micromol/kg (20 mg/kg)/day, p.o. for 7 days]. To evaluate the genotoxicity of each SERM, the presence of bulky DNA adducts was determined by (32)P-postlabeling/polyacrylamide gel electrophoresis and (32)P-postlabeling/high-performance liquid chromatography. The formation of 7,8-dihydro-8-oxodeoxyguanosine (8-oxodG) was analyzed as a marker of typical oxidative damage, using liquid chromatography electrospray tandem mass spectrometry. Among the SERMs, bulky DNA adducts were detected in the livers of rats treated with TAM; the total amount of TAM-DNA adducts was 26.1 adducts/10(7) nucleotides. However, with a detection limit of approximately 2 adducts/10(9) nucleotides, no bulky DNA adducts were observed with 4-OHTAM, TOR, RAL, or ICI 182,780. In addition, no significant increase of hepatic 8-oxodG lesions was detected in rats treated with any of the antiestrogens. Therefore, TOR, RAL, and ICI 182,780 are likely to be less genotoxic than TAM.

8-Hydroxy-2'-Deoxyguanosine↗
PubMedDate not supplied

Lasofoxifene enhances vaginal mucus formation without causing hypertrophy and increases estrogen receptor beta and androgen receptor in rats.

OBJECTIVE: Lasofoxifene, a new selective estrogen-receptor modulator (SERM), shows efficacy in vaginal and vulvar atrophy in postmenopausal women. Here, we sought to explore the possible mechanisms of action for this effect in comparison with other SERMs using an immature ovariectomized rat model. DESIGN: SERMs (lasofoxifene, raloxifene, and tamoxifen) and 17alpha-ethinyl estradiol were administered orally to immature ovariectomized rats daily for 1 or 4 days. Vaginal and uterine tissues were weighed and processed for histomorphometric measurements, vaginal mucopolysaccharide staining, and immunohistochemistry of 5-bromo-2'-deoxyuridine and steroid receptors. Receptor quantification was determined by a novel ultrasensitive enzyme-linked immunosorbent assay method. RESULTS: Lasofoxifene and raloxifene showed a minimal increase in vaginal and uterine weight, epithelial cell proliferation, and epithelial thickness in comparison with estradiol and tamoxifen. Lasofoxifene significantly enhanced vaginal mucus formation in a dose-dependent manner. Vaginal progesterone receptor protein was increased fivefold by estradiol and all three SERMs tested. 17alpha-Ethinyl estradiol caused a significant decrease in estrogen receptor alpha, but no change with other treatments. Only lasofoxifene significantly increased vaginal estrogen receptor beta and androgen receptor protein levels. CONCLUSIONS: These results demonstrated that lasofoxifene stimulated vaginal mucus formation without causing cell proliferation in the rat reproductive tract. These effects may be due to the increased vaginal estrogen receptor beta and androgen receptor levels. This cellular and molecular profile of lasofoxifene in the vagina may account for its efficacy in the treatment of vaginal and vulvar atrophy in postmenopausal women.

Administration, Oral↗
PubMed2003

Comparing therapies for postmenopausal osteoporosis prevention and treatment.

OBJECTIVE: To review the literature concerning the efficacy of calcium, hormone replacement therapy (HRT), bisphosphonates, selective estrogen receptor modulators, and calcitonin in the prevention and treatment of postmenopausal osteoporosis. DATA SOURCES: Articles were identified through searches of the MEDLINE (1966-July 2002), EMBASE (1980-July 2002), and International Pharmaceutical Abstracts (1970-July 2002) databases using the key words osteoporosis, postmenopausal, fracture, calcium, vitamin D, hormone replacement therapy, bisphosphonates, alendronate, risedronate, raloxifene, and calcitonin. Additional references were located through review of the bibliographies of the articles cited. Searches were not limited by time restriction, language, or human subject. STUDY SELECTION AND DATA EXTRACTION: Experimental and observational studies of the use of calcium and antiresorptive therapies for the prevention and treatment of postmenopausal osteoporosis were selected. Articles evaluating bone mineral density (BMD) or fracture efficacy were included in this review. DATA SYNTHESIS: HRT, bisphosphonates, raloxifene, and calcitonin have demonstrated stabilization of and improvement in BMD. Randomized clinical trials have shown fracture risk reduction with bisphosphonates, raloxifene, HRT, calcium, and calcitonin. The largest risk reductions have been reported with use of bisphosphonates in several trials. CONCLUSIONS: Several therapeutic options with well-documented improvements in BMD and reductions in fracture risk are available to women for the prevention and treatment of postmenopausal osteoporosis.

Calcitonin↗
PubMed2005

Effect of tamoxifen on venous thromboembolic events in a breast cancer prevention trial.

BACKGROUND: Tamoxifen, a selective estrogen-receptor modulator, increases venous thromboembolic events (VTE), but the factors explaining this risk are unclear. Atherosclerosis may induce VTE, or the 2 conditions may share common risk factors. We assessed the effect of tamoxifen on VTE in a breast cancer prevention trial and studied its association with risk factors for VTE. METHODS AND RESULTS: The incidence of VTE was studied in 5408 hysterectomized women randomly assigned to tamoxifen 20 mg/d or placebo for 5 years. There were 28 VTEs on placebo and 44 on tamoxifen therapy (hazard ratio [HR]=1.63; 95% confidence interval [CI], 1.02 to 2.63), 80% of which were superficial phlebitis, accounting for all of the excess due to tamoxifen within 18 months from randomization. Compared with placebo, the risk of VTE on tamoxifen was higher in women aged 55 years or older, women with a body mass index > or =25 kg/m2, elevated blood pressure, total cholesterol > or =250 mg/dL, current smoking, and a family history of coronary heart disease (CHD). Of the 685 women with a CHD risk score > or =5 who entered the trial, 1 in the placebo arm and 13 in the tamoxifen arm developed VTE (log-rank P=0.0013). In multivariate regression analysis, age > or =60 years, height > or =165 cm, and diastolic blood pressure > or =90 mm Hg had independent detrimental effects on VTE risk during tamoxifen therapy, whereas transdermal estrogen therapy concomitant with tamoxifen was not associated with any excess of VTE (HR=0.64; 95% CI, 0.23 to 1.82). CONCLUSIONS: Women with conventional risk factors for atherosclerosis have a higher risk of VTE during tamoxifen therapy. This information should be incorporated into counseling women on its risk-benefit ratio, particularly in the prevention setting.

Adult↗
PubMed2001

Raloxifene affects brain activation patterns in postmenopausal women during visual encoding.

Recent brain imaging studies have shown that estrogens alter brain activation patterns upon working memory tasks in postmenopausal women. Estrogens, however, have many systemic side effects. We investigated the effect of the Selective estrogen receptor modulator (SERM) raloxifene on brain activation patterns during a memory task in postmenopausal women with functional magnetic resonance imaging (fMRI). Twenty postmenopausal and right handed women (mean age 65.7 years; SD 3.0) were included in this double blind, placebo controlled and randomized study. Whole brain fMRI was performed before and after three months of daily treatment with raloxifene 60 mg or placebo. Each scanning session consisted of a visual encoding task, a recognition test and a simple photic simulation test. Data analyses was performed with SPM99b software. Specific regions of interest for the tasks were defined based in previous experiments. Visual encoding activated the ventral route, posterior medial temporal lobe and frontal cortex in both groups. Treatment interactions for raloxifene compared to placebo were a decrease in activation in the left parahippocampal gyrus and left lingual gyrus, an increase in activation in the right superior frontal gyrus. The mean recognition test and the simple photic stimulation test showed no treatment interactions. Our results show that raloxifene affects brain activation patterns upon visual encoding in postmenopausal women.

Aged↗
PubMed2001

Drug-Induced lipid changes: a review of the unintended effects of some commonly used drugs on serum lipid levels.

Many drugs besides lipid-lowering drugs affect serum lipid levels in either a potentially harmful or beneficial way, and may therefore increase or decrease the risk of cardiovascular disease. Diuretics, beta-blocking agents, progestogens, combined oral contraceptives containing 'second generation' progestogens, danazol, immunosuppressive agents, protease inhibitors and enzyme-inducing anticonvulsants adversely affect the lipid profile. They increase total cholesterol, low density lipoprotein cholesterol and triglycerides by up to 40, 50 and 300%, respectively, and decrease high density lipoprotein cholesterol by a maximum of 50%. Conversely, alpha-blocking agents, estrogens, hormone replacement therapy, combined oral contraceptives containing 'third generation' progestogens, selective estrogen receptor modulators, growth hormone and valproic acid show mostly beneficial effects on the lipd profile. Some drugs, for example, isotretinoin, acitretin and antipsychotics, mainly elevate triglyceride levels. Adverse or beneficial effects on serum cholesterol levels do not always translate into a higher or lower, respectively, incidence of cardiovascular disease. because these drugs may influence cardiovascular risk through multiple pathways. In some cases, excessive cholesterol levels occur, for example, with protease inhibitor therapy, and several cases of pancreatitis attributable to drug-induced hypertriglyceridaemia have been reported. Some general guidelines on the management of drug-induced dyslipidaemia can be given. Replacement of the dyslipidaemia-inducing drug by an equivalent alternative therapy is preferred. However, such alternatives are often difficult to find. If there is no equivalent alternative and treatment with the dyslipidaemia-inducing drug must be initiated, monitoring of serum lipid levels is important. If drug use is expected to be long term, the existing guidelines for the management of dyslipidaemia in the general population can be applied to drug-induced dyslipidaemia. In cases of extreme hyperlipidaemia, medication use should be reassessed.

Adult↗
PubMed2002

Mood effect of raloxifene in postmenopausal women.

OBJECTIVE: Some experimental and observational data suggest a role of estrogen in depression. Raloxifene is a selective estrogen receptor modulator (SERM) approved for the prevention and treatment of postmenopausal osteoporosis. Its influence on mood in postmenopausal women has not been fully established. Thus, we investigated the effect of raloxifene on mood. METHODS: In a randomized double-blind osteoporosis prevention study, the action of raloxifene on mood was assessed in a subgroup of non-depressed postmenopausal women (mean age: 58.9 years) receiving raloxifene 60 mg/day (n=18) or placebo (n=18). The Hamilton Depression Rating Scale (HDRS) was applied to evaluate mood 3 and 12 months following treatment. RESULTS: Baseline HDRS scores were not different among treatment groups. Overall scores decreased from baseline at 3 and 12 months in the raloxifene group (P<or=0.006), but not in the placebo group. Depression and anxiety indexes decreased in the raloxifene group at 3 and 12 months (P<or=0.04); only anxiety index at 12 months decreased in the placebo group (P=0.045). CONCLUSIONS: These preliminary results suggest that raloxifene does not negatively influence mood in non-depressed, younger postmenopausal women. Larger, long-term studies are required to evaluate a possible mood improvement effect of raloxifene.

Administration, Oral↗
PubMed2001

Raloxifene and estrogen reduces progression of advanced atherosclerosis--a study in ovariectomized, cholesterol-fed rabbits.

The present study investigated the effect of raloxifene, a selective estrogen receptor modulator (SERM), on aortic atherosclerosis in 80 ovariectomized, cholesterol-fed rabbits with pre-induced atherosclerosis. The animals were fed an atherogenic diet containing 240 mg cholesterol/day for 15 weeks, after this period a baseline control group was sacrificed. Thereafter, oral treatment was initiated with either estradiol 4 mg/day (n=20), raloxifene (210 mg/day) or placebo (n=20). In the treatment period of 39 weeks, the dietary cholesterol content was reduced to 80 mg cholesterol/day. Postmortem evaluation showed a significantly increased uterine weight induced by estradiol treatment (10.3+/-1.2 g), whereas raloxifene intervention caused a decreased uterus weight (1.21+/-0.1 g) when compared to placebo (2.48+/-0.47 g). Throughout the study, serum lipids increased in all groups to levels seen in very high risk humans. After 58 weeks the cholesterol content in the aorta was 3.18+/-0.54 micromol/cm(2) (38% reduction) in the estradiol group, 3.66+/-0.52 micromol/cm(2) (29% reduction) in the raloxifene group and 5.12+/-0.60 micromol/cm(2) in the placebo group. Analyses of the aortic cholesterol content corrected for time-averaged serum cholesterol revealed that both estradiol and raloxifene therapy significantly reduced the progression of atherosclerosis (P<0.01 for both) as compared to placebo.

Animals↗
PubMed2001

SERMs, ethnicity, and clinical trials: opportunities and challenges.

Selective estrogen receptor modulators (SERMs) are an exciting new class of pharmacotherapeutics that may have application in a wide variety of disease states. The science, both basic and clinical, that would guide the usage of these agents is in some respects at a relatively early developmental stage. Thus, the research community has an opportunity, before their use becomes widespread, to structure clinical trials such that the most complete profiles of benefits and risks are described. Tamoxifen is the SERM that has been most extensively studied and for which there are indications for both treatment and prevention of breast cancer based on trials involving more than 50,000 women. Despite this seemingly adequate sample size, an extremely important question remains unanswered--namely, whether there are ethnic differences in benefit and adverse effects of SERMs. It has generally been the case that new pharmacologic agents are tested in relatively small numbers of subjects, often only male, in North America and western Europe. While the populations are multi-ethnic, clinical trial subjects are most often not representative of the ethnic variability of these areas. Guidelines for usage of new drugs based on data from small, ethnically limited population groups are then generalized to other population groups, without consideration that differences in drug metabolism and/or responsiveness might exist.

Black People↗
PubMed2005

Comparison of tamoxifen and clomiphene citrate for ovulation induction: a meta-analysis.

BACKGROUND: Both selective estrogen receptor modulators, tamoxifen and clomiphene have been used for ovulation induction for patients with anovulatory infertility. This meta-analysis sought to compare the effectiveness of tamoxifen to clomiphene for the induction of ovulation and achievement of pregnancy. METHODS: We searched MEDLINE, BIOSIS, PreMEDLINE, CINAHL, International Pharmaceutical Abstracts, DDSR, ACP Journal Club, DARE and CCTR, along with reference lists and national experts. Inclusion criteria were prospective clinical trials, which compared tamoxifen and clomiphene for ovulation induction in infertile couples with isolated anovulatory infertility. Main outcome measures were ovulation rate and clinical pregnancy rate. Pooled odds ratios were obtained using random effects meta-analysis. RESULTS: Four trials were included. After pooling all the trials, the use of tamoxifen or clomiphene citrate resulted in similar ovulation rates [odds ratio (OR) 0.755, 95% confidence interval (CI) 0.513-1.111]. There was no benefit of tamoxifen over clomiphene citrate in achievement of pregnancy per cycle (OR 1.056, 95% CI 0.583-1.912) or per ovulatory cycle (OR 1.162, 95% CI 0.632-2.134). CONCLUSIONS: Clomiphene citrate and tamoxifen are equally effective in inducing ovulation. Although data regarding pregnancy rates and outcome are limited, there does not appear to be a significant benefit of one medication over the other.

Adolescent↗
PubMed2003

Effect of raloxifene on lowering lipid parameters in patients with osteoporosis.

The aim of this study was to show the effect of raloxifene on the lowering of lipid parameters in patients with osteoporosis. New investigations introduced selective estrogen receptor modulators (SERMs), such as raloxifene, as a potent drug in the lowering of lipid parameters. Raloxifene is known as a substance that works well in preventing and treating osteoporosis. We investigated the effect of raloxifene on the lowering of lipid parameters (cholesterol and triglycerides) in 94 women who took 60 mg/day of raloxifene for the treatment of osteoporosis. We performed three measurements of cholesterol and triglycerides, at the beginning of the study and at 3 and 12 months. Bone mineral density (BMD) was measured at the begining and at 12 months; spine BMD increased 2.7%. The mean value of cholesterol was 6.6961 mmol/l at the beginning, 6.060 mmol/l at 3 months and 5.826 mmol/l at 12 months. The difference between mean values was statistically significant at p < 0.01. Mean values of triglycerides were 2.153 mmol/l at the beginning, 1.970 mmol/l at 3 months and 1.680 mmol/l at 12 months. The difference between mean values at 3 months was statistically significant at p < 0.05 and at 12 months at p < 0.01. We concluded that raloxifene had significant effects on lowering cholesterol and triglycerides in postmenopausal women and that raloxifene is the best choice in the treatment of osteoporosis and moderate lipid disorders.

Aged↗