human
***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: Currently raloxifene , a selective estrogen receptor modulator , is being investigated as a potential alternative for postmenopausal hormone replacement to prevent osteoporosis and cardiovascular disease . We compared the 2-year effects of raloxifene on a wide range of cardiovascular risk factors with those of placebo and conjugated equine estrogens ( CEEs ) . Analyses were based on 56 hysterectomized but otherwise healthy postmenopausal women aged 54 . 8+/-3.5 ( mean+/-SD ) years who entered this double-blind study and who were r and omly assigned to raloxifene hydrochloride 60 mg/d ( n=15 ) or 150 mg/d ( n=13 ) , placebo ( n=13 ) , or CEEs 0.625 mg/d ( n=15 ) . At baseline and after 6 , 12 , and 24 months of treatment , we assessed serum lipids , blood pressure , glucose metabolism , C-reactive protein , and various hemostatic parameters . Compared with placebo , both raloxifene and CEEs lowered the level of low density lipoprotein cholesterol by 0.53 to 0.79 mmol/L ( all P<0.04 ) and lowered , at 24 months , the level of fibrinogen by 0.71 to 0.86 g/L ( all P<0.05 ) . The effects of raloxifene and CEEs did not differ significantly . In contrast to raloxifene , from 6 months on CEEs increased high density lipoprotein cholesterol by 0.25 to 0.29 mmol/L and reduced plasminogen activator inhibitor-1 antigen by 30.6 to 48.6 ng/mL ( all P<0.02 versus both placebo and raloxifene ) . CEEs transiently increased C-reactive protein by 1.0 mg/L at 6 months ( P<0.05 versus placebo ) and prothrombin-derived fragment F1 + 2 by 0 . 79 nmol/L at 12 months ( P<0.001 versus placebo ) . Finally , from 12 months on , CEEs increased triglycerides by 0.33 to 0.56 mmol/L ( all P<0.05 versus both placebo and raloxifene ) . Our findings suggest that in healthy postmenopausal women , raloxifene and estrogen monotherapy have similar beneficial effects on low density lipoprotein cholesterol and fibrinogen levels . These treatments differ , however , in their effects on high density lipoprotein cholesterol , triglycerides , and plasminogen activator inhibitor-1 and possibly in their effects on prothrombin fragment F1 + 2 and C-reactive protein CONTEXT The effects of continuous combined hormone therapy on gynecologic cancers have not been investigated previously in a r and omized trial setting . OBJECTIVE To determine the possible associations of estrogen plus progestin on gynecologic cancers and related diagnostic procedures . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial of 16 608 postmenopausal women , who had not had a hysterectomy at baseline and who had been recruited from 40 US clinical centers between September 1993 and October 1998 ( average follow-up , 5.6 years ) . INTERVENTION One tablet per day containing 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOME MEASURE Incident invasive cancer of the ovary and endometrium . RESULTS In 5.6 years of follow-up , there were 32 cases of invasive ovarian cancer , 58 cases of endometrial cancer , 1 case of nonendometrial uterine cancer , 13 cases of cervical cancer , and 7 cases of other gynecologic cancers . The hazard ratio ( HR ) for invasive ovarian cancer in women assigned to estrogen plus progestin compared with placebo was 1.58 ( 95 % confidence interval [ CI ] , 0.77 - 3.24 ) . The HR for endometrial cancer was 0.81 ( 95 % CI , 0.48 - 1.36 ) . No appreciable differences were found in the distributions of tumor histology , stage , or grade for either cancer site . The incidence of other gynecologic cancers was low and did not differ by r and omization assignment . More women taking estrogen plus progestin required endometrial biopsies ( 33 % vs 6 % ; P<.001 ) . CONCLUSIONS This r and omized trial suggests that continuous combined estrogen plus progestin therapy may increase the risk of ovarian cancer while producing endometrial cancer rates similar to placebo . The increased burden of endometrial biopsies required to assess vaginal bleeding further limits the acceptability of this regimen . These data provide additional support for caution in the use of continuous combined hormones Background — The Women ’s Health Initiative ( WHI ) Estrogen Alone trial assessed the balance of benefits and risks of hormone use in healthy postmenopausal women . The trial was stopped prematurely because there was no benefit for coronary heart disease and an increased risk of stroke . This report provides a thorough analysis of the stroke finding using the final results from the completed trial data base . Methods and Results — The WHI Estrogen Alone hormone trial is a multicenter , double-blind , placebo-controlled , r and omized clinical trial in 10 739 women aged 50 to 79 years who were given daily conjugated equine estrogen ( CEE ; 0.625 mg ; n=5310 ) or placebo ( n=5429 ) . During an average follow-up of 7.1 years , there were 168 strokes in the CEE group and 127 in the placebo group ; 80.3 % of strokes were ischemic . For all stroke the intention-to-treat hazard ratio [ HR ] ( 95 % CI ) for CEE versus placebo was 1.37 ( 1.09 to 1.73 ) . The HR ( 95 % CI ) was 1.55 ( 1.19 to 2.01 ) for ischemic stroke and 0.64 ( 0.35 , 1.18 ) for hemorrhagic stroke . The HRs indicate excess risk of ischemic stroke was apparent in all categories of baseline stroke risk , including younger and more recently menopausal women and in women with prior or current use of statins or aspirin . Conclusions — CEE increases the risk of ischemic stroke in generally healthy postmenopausal women . The excess risk appeared to be present in all subgroups of women examined , including younger and more recently menopausal women . There was no convincing evidence to suggest that CEE had an effect on the risk of hemorrhagic stroke Background Menopausal hormone therapy ( MHT ) reportedly increases the risk of cognitive decline in women over age 65 y. It is unknown whether similar risks exist for recently postmenopausal women , and whether MHT affects mood in younger women . The ancillary Cognitive and Affective Study ( KEEPS-Cog ) of the Kronos Early Estrogen Prevention Study ( KEEPS ) examined the effects of up to 4 y of MHT on cognition and mood in recently postmenopausal women . Methods and Findings KEEPS , a r and omized , double-blinded , placebo-controlled clinical trial , was conducted at nine US academic centers . Of the 727 women enrolled in KEEPS , 693 ( 95.3 % ) participated in the ancillary KEEPS-Cog , with 220 women r and omized to receive 4 y of 0.45 mg/d oral conjugated equine estrogens ( o-CEE ) plus 200 mg/d micronized progesterone ( m-P ) for the first 12 d of each month , 211 women r and omized to receive 50 μg/d transdermal estradiol ( t-E2 ) plus 200 mg/d m-P for the first 12 d of each month , and 262 women r and omized to receive placebo pills and patches . Primary outcomes included the Modified Mini-Mental State examination ; four cognitive factors : verbal learning/memory , auditory attention/working memory , visual attention/executive function , and speeded language /mental flexibility ; and a mood measure , the Profile of Mood States ( POMS )  . MHT effects were analyzed using linear mixed-effects ( LME ) models , which make full use of all available data from each participant , including those with missing data . Data from those with and without full data were compared to assess for potential biases result ing from missing observations . For statistically significant results , we calculated effect sizes ( ESs ) to evaluate the magnitude of changes . On average , participants were 52.6 y old , and 1.4 y past their last menstrual period . By month 48 , 169 ( 24.4 % ) and 158 ( 22.8 % ) of the 693 women who consented for ancillary KEEPS-Cog were lost to follow-up for cognitive assessment ( 3MS and cognitive factors ) and mood evaluations ( POMS ) , respectively . However , because LME models make full use all available data , including data from women with missing data , 95.5 % of participants were included in the final analysis ( n = 662 in cognitive analyses , and n = 661 in mood analyses ) . To be included in analyses , women must have provided baseline data , and data from at least one post-baseline visit . The mean length of follow-up was 2.85 y ( st and ard deviation [ SD ] = 0.49 ) for cognitive outcomes and 2.76 ( SD = 0.57 ) for mood outcomes . No treatment-related benefits were found on cognitive outcomes . For mood , model estimates indicated that women treated with o-CEE showed improvements in depression and anxiety symptoms over the 48 mo of treatment , compared to women on placebo . The model estimate for the depression subscale was −5.36 × 10−2 ( 95 % CI , −8.27 × 10−2 to −2.44 × 10−2 ; ES = 0.49 , p < 0.001 ) and for the anxiety subscale was −3.01 × 10−2 ( 95 % CI , −5.09 × 10−2 to −9.34 × 10−3 ; ES = 0.26 , p < 0.001 ) . Mood outcomes for women r and omized to t-E2 were similar to those for women on placebo . Importantly , the KEEPS-Cog results can not be extrapolated to treatment longer than 4 y. Conclusions The KEEPS-Cog findings suggest that for recently postmenopausal women , MHT did not alter cognition as hypothesized . However , beneficial mood effects with small to medium ESs were noted with 4 y of o-CEE , but not with 4 y of t-E2 . The generalizability of these findings is limited to recently postmenopausal women with low cardiovascular risk profiles . Trial Registration Clinical Trials.gov NCT00154180 and OBJECTIVES To evaluate the effects of hormone replacement therapy ( HRT ) on lipids and lipoproteins in postmenopausal women with coronary artery disease . SETTING In this single-centre , controlled and r and omized study taking place in a tertiary referral clinic , patients were examined at baseline , and after 3 and 12 months . All analyses were performed examiner-blind . SUBJECTS Postmenopausal women ( n = 118 ) with angiographically verified coronary artery disease were recruited consecutively from patients referred for investigational procedures due to coronary artery disease . INTERVENTIONS The women were r and omized to HRT , i.e. transdermal application of continuous 17-beta oestradiol with cyclic medroxyprogesterone actetate tablets every 3rd month for 14 days , or to a control group . MAIN OUTCOMES Effects on lipids and lipoproteins . RESULTS After 3 months of unopposed oestradiol , triglycerides decreased significantly compared to the control group ( P = 0.006 ) . Sequential administration of medroxyprogesterone caused a decrease in HDL cholesterol ( P = 0.01 ) , concomitantly with a decrease in ApoA1 lipoproteins ( P = 0.007 ) . No other changes in lipids or lipoproteins were observed . After 12 months of therapy , no significant differences were observed between the two groups in lipid or lipoprotein levels . Concomitant statin treatment did not alter the main findings . CONCLUSIONS In postmenopausal women with established coronary artery disease in whom the majority is treated with statins , no additional effect of HRT on lipids or lipoproteins could be observed except for a transient decrease in triglycerides in the initial unopposed oestradiol phase . No deleterious effect could be observed during medroxyprogesterone administration except for a small transient decrease in HDL cholesterol and ApoA1 lipoproteins Abstract —Postmenopausal hormone replacement therapy ( HRT ) is associated with low cardiovascular morbidity and mortality in epidemiological studies . Yet , no r and omized trial has examined whether HRT is effective for prevention of coronary heart disease ( CHD ) in women with increased risk . The objective of this 
    Output:
    
agent
Women taking HT had a significantly decreased incidence of fracture with long-term use .
Research ers found no strong evidence that HT has a clinical ly meaningful impact on the incidence of colorectal cancer .
AUTHORS ' CONCLUSIONS : Women with intolerable menopausal symptoms may wish to weigh the benefits of symptom relief against the small absolute risk of harm arising from short-term use of low-dose HT , provided they do not have specific contraindications .
HT may be unsuitable for some women , including those at increased risk of cardiovascular disease , increased risk of thromboembolic disease ( such as those with obesity or a history of venous thrombosis ) or increased risk of some types of cancer ( such as breast cancer , in women with a uterus ) .
The risk of endometrial cancer among women with a uterus taking oestrogen-only HT is well documented .
HT is not indicated for primary or secondary prevention of cardiovascular disease or dementia , nor for prevention of deterioration of cognitive function in postmenopausal women .
Although HT is considered effective for the prevention of postmenopausal osteoporosis , it is generally recommended as an option only for women at significant risk for whom non-oestrogen therapies are unsuitable .
***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: Currently raloxifene , a selective estrogen receptor modulator , is being investigated as a potential alternative for postmenopausal hormone replacement to prevent osteoporosis and cardiovascular disease . We compared the 2-year effects of raloxifene on a wide range of cardiovascular risk factors with those of placebo and conjugated equine estrogens ( CEEs ) . Analyses were based on 56 hysterectomized but otherwise healthy postmenopausal women aged 54 . 8+/-3.5 ( mean+/-SD ) years who entered this double-blind study and who were r and omly assigned to raloxifene hydrochloride 60 mg/d ( n=15 ) or 150 mg/d ( n=13 ) , placebo ( n=13 ) , or CEEs 0.625 mg/d ( n=15 ) . At baseline and after 6 , 12 , and 24 months of treatment , we assessed serum lipids , blood pressure , glucose metabolism , C-reactive protein , and various hemostatic parameters . Compared with placebo , both raloxifene and CEEs lowered the level of low density lipoprotein cholesterol by 0.53 to 0.79 mmol/L ( all P<0.04 ) and lowered , at 24 months , the level of fibrinogen by 0.71 to 0.86 g/L ( all P<0.05 ) . The effects of raloxifene and CEEs did not differ significantly . In contrast to raloxifene , from 6 months on CEEs increased high density lipoprotein cholesterol by 0.25 to 0.29 mmol/L and reduced plasminogen activator inhibitor-1 antigen by 30.6 to 48.6 ng/mL ( all P<0.02 versus both placebo and raloxifene ) . CEEs transiently increased C-reactive protein by 1.0 mg/L at 6 months ( P<0.05 versus placebo ) and prothrombin-derived fragment F1 + 2 by 0 . 79 nmol/L at 12 months ( P<0.001 versus placebo ) . Finally , from 12 months on , CEEs increased triglycerides by 0.33 to 0.56 mmol/L ( all P<0.05 versus both placebo and raloxifene ) . Our findings suggest that in healthy postmenopausal women , raloxifene and estrogen monotherapy have similar beneficial effects on low density lipoprotein cholesterol and fibrinogen levels . These treatments differ , however , in their effects on high density lipoprotein cholesterol , triglycerides , and plasminogen activator inhibitor-1 and possibly in their effects on prothrombin fragment F1 + 2 and C-reactive protein CONTEXT The effects of continuous combined hormone therapy on gynecologic cancers have not been investigated previously in a r and omized trial setting . OBJECTIVE To determine the possible associations of estrogen plus progestin on gynecologic cancers and related diagnostic procedures . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial of 16 608 postmenopausal women , who had not had a hysterectomy at baseline and who had been recruited from 40 US clinical centers between September 1993 and October 1998 ( average follow-up , 5.6 years ) . INTERVENTION One tablet per day containing 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate ( n = 8506 ) or placebo ( n = 8102 ) . MAIN OUTCOME MEASURE Incident invasive cancer of the ovary and endometrium . RESULTS In 5.6 years of follow-up , there were 32 cases of invasive ovarian cancer , 58 cases of endometrial cancer , 1 case of nonendometrial uterine cancer , 13 cases of cervical cancer , and 7 cases of other gynecologic cancers . The hazard ratio ( HR ) for invasive ovarian cancer in women assigned to estrogen plus progestin compared with placebo was 1.58 ( 95 % confidence interval [ CI ] , 0.77 - 3.24 ) . The HR for endometrial cancer was 0.81 ( 95 % CI , 0.48 - 1.36 ) . No appreciable differences were found in the distributions of tumor histology , stage , or grade for either cancer site . The incidence of other gynecologic cancers was low and did not differ by r and omization assignment . More women taking estrogen plus progestin required endometrial biopsies ( 33 % vs 6 % ; P<.001 ) . CONCLUSIONS This r and omized trial suggests that continuous combined estrogen plus progestin therapy may increase the risk of ovarian cancer while producing endometrial cancer rates similar to placebo . The increased burden of endometrial biopsies required to assess vaginal bleeding further limits the acceptability of this regimen . These data provide additional support for caution in the use of continuous combined hormones Background — The Women ’s Health Initiative ( WHI ) Estrogen Alone trial assessed the balance of benefits and risks of hormone use in healthy postmenopausal women . The trial was stopped prematurely because there was no benefit for coronary heart disease and an increased risk of stroke . This report provides a thorough analysis of the stroke finding using the final results from the completed trial data base . Methods and Results — The WHI Estrogen Alone hormone trial is a multicenter , double-blind , placebo-controlled , r and omized clinical trial in 10 739 women aged 50 to 79 years who were given daily conjugated equine estrogen ( CEE ; 0.625 mg ; n=5310 ) or placebo ( n=5429 ) . During an average follow-up of 7.1 years , there were 168 strokes in the CEE group and 127 in the placebo group ; 80.3 % of strokes were ischemic . For all stroke the intention-to-treat hazard ratio [ HR ] ( 95 % CI ) for CEE versus placebo was 1.37 ( 1.09 to 1.73 ) . The HR ( 95 % CI ) was 1.55 ( 1.19 to 2.01 ) for ischemic stroke and 0.64 ( 0.35 , 1.18 ) for hemorrhagic stroke . The HRs indicate excess risk of ischemic stroke was apparent in all categories of baseline stroke risk , including younger and more recently menopausal women and in women with prior or current use of statins or aspirin . Conclusions — CEE increases the risk of ischemic stroke in generally healthy postmenopausal women . The excess risk appeared to be present in all subgroups of women examined , including younger and more recently menopausal women . There was no convincing evidence to suggest that CEE had an effect on the risk of hemorrhagic stroke Background Menopausal hormone therapy ( MHT ) reportedly increases the risk of cognitive decline in women over age 65 y. It is unknown whether similar risks exist for recently postmenopausal women , and whether MHT affects mood in younger women . The ancillary Cognitive and Affective Study ( KEEPS-Cog ) of the Kronos Early Estrogen Prevention Study ( KEEPS ) examined the effects of up to 4 y of MHT on cognition and mood in recently postmenopausal women . Methods and Findings KEEPS , a r and omized , double-blinded , placebo-controlled clinical trial , was conducted at nine US academic centers . Of the 727 women enrolled in KEEPS , 693 ( 95.3 % ) participated in the ancillary KEEPS-Cog , with 220 women r and omized to receive 4 y of 0.45 mg/d oral conjugated equine estrogens ( o-CEE ) plus 200 mg/d micronized progesterone ( m-P ) for the first 12 d of each month , 211 women r and omized to receive 50 μg/d transdermal estradiol ( t-E2 ) plus 200 mg/d m-P for the first 12 d of each month , and 262 women r and omized to receive placebo pills and patches . Primary outcomes included the Modified Mini-Mental State examination ; four cognitive factors : verbal learning/memory , auditory attention/working memory , visual attention/executive function , and speeded language /mental flexibility ; and a mood measure , the Profile of Mood States ( POMS )  . MHT effects were analyzed using linear mixed-effects ( LME ) models , which make full use of all available data from each participant , including those with missing data . Data from those with and without full data were compared to assess for potential biases result ing from missing observations . For statistically significant results , we calculated effect sizes ( ESs ) to evaluate the magnitude of changes . On average , participants were 52.6 y old , and 1.4 y past their last menstrual period . By month 48 , 169 ( 24.4 % ) and 158 ( 22.8 % ) of the 693 women who consented for ancillary KEEPS-Cog were lost to follow-up for cognitive assessment ( 3MS and cognitive factors ) and mood evaluations ( POMS ) , respectively . However , because LME models make full use all available data , including data from women with missing data , 95.5 % of participants were included in the final analysis ( n = 662 in cognitive analyses , and n = 661 in mood analyses ) . To be included in analyses , women must have provided baseline data , and data from at least one post-baseline visit . The mean length of follow-up was 2.85 y ( st and ard deviation [ SD ] = 0.49 ) for cognitive outcomes and 2.76 ( SD = 0.57 ) for mood outcomes . No treatment-related benefits were found on cognitive outcomes . For mood , model estimates indicated that women treated with o-CEE showed improvements in depression and anxiety symptoms over the 48 mo of treatment , compared to women on placebo . The model estimate for the depression subscale was −5.36 × 10−2 ( 95 % CI , −8.27 × 10−2 to −2.44 × 10−2 ; ES = 0.49 , p < 0.001 ) and for the anxiety subscale was −3.01 × 10−2 ( 95 % CI , −5.09 × 10−2 to −9.34 × 10−3 ; ES = 0.26 , p < 0.001 ) . Mood outcomes for women r and omized to t-E2 were similar to those for women on placebo . Importantly , the KEEPS-Cog results can not be extrapolated to treatment longer than 4 y. Conclusions The KEEPS-Cog findings suggest that for recently postmenopausal women , MHT did not alter cognition as hypothesized . However , beneficial mood effects with small to medium ESs were noted with 4 y of o-CEE , but not with 4 y of t-E2 . The generalizability of these findings is limited to recently postmenopausal women with low cardiovascular risk profiles . Trial Registration Clinical Trials.gov NCT00154180 and OBJECTIVES To evaluate the effects of hormone replacement therapy ( HRT ) on lipids and lipoproteins in postmenopausal women with coronary artery disease . SETTING In this single-centre , controlled and r and omized study taking place in a tertiary referral clinic , patients were examined at baseline , and after 3 and 12 months . All analyses were performed examiner-blind . SUBJECTS Postmenopausal women ( n = 118 ) with angiographically verified coronary artery disease were recruited consecutively from patients referred for investigational procedures due to coronary artery disease . INTERVENTIONS The women were r and omized to HRT , i.e. transdermal application of continuous 17-beta oestradiol with cyclic medroxyprogesterone actetate tablets every 3rd month for 14 days , or to a control group . MAIN OUTCOMES Effects on lipids and lipoproteins . RESULTS After 3 months of unopposed oestradiol , triglycerides decreased significantly compared to the control group ( P = 0.006 ) . Sequential administration of medroxyprogesterone caused a decrease in HDL cholesterol ( P = 0.01 ) , concomitantly with a decrease in ApoA1 lipoproteins ( P = 0.007 ) . No other changes in lipids or lipoproteins were observed . After 12 months of therapy , no significant differences were observed between the two groups in lipid or lipoprotein levels . Concomitant statin treatment did not alter the main findings . CONCLUSIONS In postmenopausal women with established coronary artery disease in whom the majority is treated with statins , no additional effect of HRT on lipids or lipoproteins could be observed except for a transient decrease in triglycerides in the initial unopposed oestradiol phase . No deleterious effect could be observed during medroxyprogesterone administration except for a small transient decrease in HDL cholesterol and ApoA1 lipoproteins Abstract —Postmenopausal hormone replacement therapy ( HRT ) is associated with low cardiovascular morbidity and mortality in epidemiological studies . Yet , no r and omized trial has examined whether HRT is effective for prevention of coronary heart disease ( CHD ) in women with increased risk . The objective of this 
    Output:
    