***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVES To study the effect of st and ard and low-dose estrogen-progestin therapy ( EPT ) , tibolone and raloxifene on the incidence of  vaginal spotting/bleeding and endometrial thickness  over a 5-year period . METHODS Seven hundred eighty-six postmenopausal women were studied in an open prospect i ve design . Vaginal spotting/bleeding and endometrial thickness as assessed by transvaginal ultrasonography was compared between six categories of women over a 5-year period : three categories in women on continuous  combined estrogen-progestin therapy , one category under tibolone , one category under raloxifene and one under no treatment . More specifically , women received tibolone 2.5 mg ( N = 204 ) , raloxifene HCl 60 mg ( N = 137 ) , conjugated equine estrogens 0.625 mg/medroxyprogesterone acetate 5 mg ( N = 122 ) , 17beta-estradiol 2mg/norethisterone acetate 1 mg ( N = 58 ) , 17beta-estradiol 1mg/norethisterone acetate 0.5 mg ( N = 76 ) or no therapy ( controls , N = 189 ) . Women with suspected endometrial pathology were referred for hysteroscopy . RESULTS Bleeding/spotting incidence was highest among st and ard dose EPT users ( conjugated equine estrogens 0.625 mg/medroxyprogesterone acetate 5 mg : 40.1 % , 17beta-estradiol 2mg/norethisterone acetate 1 mg : 44.8 % , p < 0.001 compared to controls ) . Low-dose EPT associated with lower incidence of spotting/bleeding ( 34.1 % ) . The incidence under tibolone and raloxifene was 22.5 % and 2.9 % , respectively , while 3.2 % of women not receiving therapy reported vaginal spotting/bleeding . Mean endometrial thickness was not significantly affected in any of the groups studied . The drop-out rate due to spotting/bleeding was higher in the two higher dose EPT regimens . After logistic regression analysis , age at baseline was the only significant predictor of subsequent spotting/bleeding ( b = -0.25 , S.E. = 0.09 , p = 0.006 ) , while menopausal age and pre-treatment serum FSH had marginal significance . CONCLUSIONS EPT , tibolone and raloxifene do not appear to associate with significant changes in endometrial thickness in the majority of cases . The low-dose EPT regimen associated with a decreased incidence of unscheduled spotting/bleeding compared to the st and ard dose regimens . Tibolone expressed a favorable endometrial profile , as seen in its effect on unscheduled spotting/bleeding and mean endometrial thickness .  Raloxifene associated with the lowest incidence in S/B and the lowest drop-out rate.s Raloxifene is a selective estrogen receptor modulator that in experimental animals acts as an estrogen receptor antagonist in breast and endometrium but as an estrogen receptor agonist in the skeletal and cardiovascular systems . We conducted a 1-year prospect i ve , r and omized , double-blind trial in 143 postmenopausal osteoporotic women ( mean + /- SD age , 68.4+/-5.0 years ) with at least one prevalent vertebral fractures and low bone mineral density ( BMD ) , comparing groups receiving raloxifene at 60 mg/day ( RLX60 ) or 120 mg/day ( RLX120 ) and a control group receiving supplements of 750 mg/day of calcium and 400 IU/day of vitamin D.  There were no differences among groups in the occurrence of uterine bleeding , thrombophlebitis , breast abnormalities , or increased endometrial thickness ( assessed by ultrasonography ) . As compared with controls , the changes in values over 1 year for RLX60 and RLX120 , respectively , were significant for serum bone alkaline phosphatase ( -14.9 % , -8.87 % ) , serum osteocalcin ( -20.7 % , -17.0 % ) , and urinary C-telopeptide fragment of type I collagen/creatinine ( -24.9 % , -30.8 % ) , markers of bone turnover ; for serum total cholesterol ( -7.0 % for RLX60 ) and low density lipoprotein cholesterol ( LDL ) ( -11.4 % for RLX60 ) and for the LDL/HDL cholesterol ratio ( -13.2 % , -8.3 % ) . BMD increased significantly in the total hip ( 1.66 % for RLX60 ) and ultradistal radius ( 2.92 % , 2.50 % ) . There were nonsignificant trends toward increases over controls in BMD for lumbar spine , total body , and total hip ( for RLX120 ) . Using a > 15 % cutoff definition , raloxifene had no effect on incident fractures , but using a > 30 % cutoff , there was a dose-related reduction ( p = 0.047 ) . We conclude that raloxifene therapy is well tolerated , reduces serum lipids , and does not stimulate the uterus or breasts . It has beneficial effects on bone , although , under the conditions of this study , these appear to be of a smaller magnitude than have been reported with estrogen therapy BACKGROUND Three clinical trials on the use of tamoxifen to prevent breast cancer have reported mixed results . The overall evidence supports a reduction in the risk of breast cancer , but whether this benefit outweighs the risks and side-effects associated with tamoxifen is unclear . METHODS We undertook a double-blind placebo-controlled r and omised trial of tamoxifen , 20 mg/day for 5 years , in 7152 women aged 35 - 70 years , who were at increased risk of breast cancer . The primary outcome measure was the frequency of breast cancer ( including ductal carcinoma in situ ) . Analyses were by intention to treat after exclusion of 13 women found to have breast cancer at baseline mammography . FINDINGS After median follow-up of 50 months ( IQR 32 - 67 ) , 69 breast cancers had been diagnosed in 3578 women in the tamoxifen group and 101 in 3566 in the placebo group ( risk reduction 32 % [ 95 % CI 8 - 50 ] ; p=0.013 ) . Age , degree of risk , and use of hormone-replacement therapy did not affect the reduction . Endometrial cancer was non-significantly increased ( 11 vs 5 ; p=0.2 ) and thromboembolic events were significantly increased with tamoxifen ( 43 vs 17 ; odds ratio 2.5 [ 1.5 - 4.4 ] , p=0.001 ) , particularly after surgery . There was a significant excess of deaths from all causes in the tamoxifen group ( 25 vs 11 , p=0.028 ) . INTERPRETATION Prophylactic tamoxifen reduces the risk of breast cancer by about a third . Temporary cessation of tamoxifen should be considered and the use of appropriate antithrombotic measures is recommended during and after major surgery or periods of immobilisation . Prophylactic use of tamoxifen is contraindicated in women at high risk of thromboembolic disease . The combined evidence indicates that mortality from non-breast-cancer causes is not increased by tamoxifen . The overall risk to benefit ratio for the use of tamoxifen in prevention is still unclear , and continued follow-up of the current trials is essential Abstract : Raloxifene , a selective estrogen receptor modulator ( SERM ) , has been shown to improved bone mineral density ( BMD ) and serum lipid profiles in healthy postmenopausal women . The objective of this study was to examine the effects of raloxifene on BMD , biochemical markers of bone metabolism and serum lipids in postmenopausal women with low bone density or osteoporosis . This Phase II , multicenter , 24-month , double-masked study assessed the efficacy and safety of raloxifene in 129 postmenopausal women ( mean age ± SD : 60.2 ± 6.7 years ) with osteoporosis or low bone density ( baseline mean lumbar spine BMD T-score : −2.8 ) . Women were r and omly assigned to one of three treatment groups : placebo , 60 mg/day raloxifene-HCl ( RLX 60 ) or 150 mg/day raloxifene-HCl ( RLX 150 ) and concomitantly received 1000 mg/day calcium and 300 U/day vitamin D3 . At 24 months , BMD was significantly increased in the lumbar spine ( + 3.2 % ) , femoral neck ( + 2.1 % ) , trochanter ( + 2.7 % ) and total hip ( + 1.6 % ) in the RLX 60 group compared with the placebo group ( p<0.05 ) . The RLX 150 group had increases in BMD similar to those observed with RLX 60 . A greater percentage of raloxifene-treated patients , compared with those receiving placebo , had increased BMD ( p<0.05 ) . Serum bone-specific alkaline phosphatase activity , serum osteocalcin , and urinary type I collagen : creatinine ratio were significantly decreased in the RLX-treated groups , compared with the placebo group ( p<0.01 ) . RLX 60 treatment significantly decreased serum levels of triglycerides , and total- and LDL-cholesterol levels ( p<0.01 ) . The rates of patient discontinuation and adverse events were not significantly different among groups . In this study , raloxifene increased bone density , decreased bone turnover , and improved the serum lipid profile with minimal adverse events , and may be a safe and effective treatment for postmenopausal women with osteoporosis or low bone density The selective estrogen-receptor modulator ( SERM ) tamoxifen became the first U.S. Food and Drug Administration ( FDA ) –approved agent for reducing breast cancer risk but did not gain wide acceptance for prevention , largely because it increased endometrial cancer and thromboembolic events . The FDA approved the SERM raloxifene for breast cancer risk reduction following its demonstrated effectiveness in preventing invasive breast cancer in the Study of Tamoxifen and Raloxifene ( STAR ) .  Raloxifene caused less toxicity ( versus tamoxifen ) , including reduced thromboembolic events and endometrial cancer . In this report , we present an up date d analysis with an 81-month median follow-up . STAR women were r and omly assigned to receive either tamoxifen ( 20 mg/d ) or raloxifene ( 60 mg/d ) for 5 years . The risk ratio ( RR  ; raloxifene : tamoxifen )  for invasive breast cancer was 1.24 ( 95 % confidence interval [ CI ] , 1.05–1.47 ) and for noninvasive disease , 1.22 ( 95 % CI , 0.95–1.59 ) . Compared with initial results , the RRs widened for invasive and narrowed for noninvasive breast cancer . Toxicity RRs  ( raloxifene : tamoxifen ) were 0.55 ( 95 % CI , 0.36–0.83 ; P = 0.003 ) for endometrial cancer ( this difference was not significant in the initial results ) , 0.19 ( 95 % CI , 0.12–0.29 ) for uterine hyperplasia , and 0.75 ( 95 % CI , 0.60–0.93 ) for thromboembolic events . There were no significant mortality differences . Long-term raloxifene retained 76 % of the effectiveness of tamoxifen in preventing invasive disease and grew closer over time to tamoxifen in preventing noninvasive disease , with far less toxicity ( e.g. , highly significantly less endometrial cancer ) . These results have important public health implication s and clarify that both raloxifene and tamoxifen are good preventive choices for postmenopausal women with elevated risk for breast cancer . Cancer Prev Res ; 3(6 ) ; 696–706 . © 2010 AACR The Multiple Outcomes of Raloxifene Evaluation trial studied 7705 postmenopausal women with osteoporosis r and omized to placebo , or raloxifene 60 or 120 mg/d [ JAMA 282(1999 ) : 637 ] . This report assesses the efficacy of raloxifene on the long-term cumulative incidence new vertebral fractures through 4 yr . New vertebral fractures was assessed from radiographs taken at baseline , yr 2 - 4 . The primary analysis was the cumulative incidence of new vertebral fractures through 4 yr . A posthoc analysis compared the vertebral fracture risk in yr 4 alone with that observed in the first 3 yr . The 4-yr cumulative relative risks ( RR ) for one or more new vertebral fractures were 0.64 [ 95 % confidence interval ( CI ) 0.53 ,  
    Output:
    
Tamoxifen increased the incidence of endometrial cancer and cataracts compared with placebo and raloxifene .
Many women do not take tamoxifen because of associated harms .
Thirteen risk-stratification models were modest predictors of breast cancer .
Medications reduced the incidence of invasive breast cancer and fractures and increased the incidence of thromboembolic events .
Tamoxifen was more effective than raloxifene but also increased the incidence of endometrial cancer and cataracts .