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: 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 CONTEXT The Women 's Health Initiative trial of combined estrogen plus progestin was stopped early when overall health risks , including invasive breast cancer , exceeded benefits . Outst and ing issues not previously addressed include characteristics of breast cancers observed among women using hormones and whether diagnosis may be influenced by hormone effects on mammography . OBJECTIVE To determine the relationship among estrogen plus progestin use , breast cancer characteristics , and mammography recommendations . DESIGN , SETTING , AND PARTICIPANTS Following a comprehensive breast cancer risk assessment , 16 608 postmenopausal women aged 50 to 79 years with an intact uterus were r and omly assigned to receive combined conjugated equine estrogens ( 0.625 mg/d ) plus medroxyprogesterone acetate ( 2.5 mg/d ) or placebo from 1993 to 1998 at 40 clinical centers . Screening mammography and clinical breast examinations were performed at baseline and yearly thereafter . MAIN OUTCOME MEASURES Breast cancer number and characteristics , and frequency of abnormal mammograms by estrogen plus progestin exposure . RESULTS In intent-to-treat analyses , estrogen plus progestin increased total ( 245 vs 185 cases ; hazard ratio [ HR ] , 1.24 ; weighted P<.001 ) and invasive ( 199 vs 150 cases ; HR , 1.24 ; weighted P = .003 ) breast cancers compared with placebo . The invasive breast cancers diagnosed in the estrogen plus progestin group were similar in histology and grade but were larger ( mean [ SD ] , 1.7 cm [ 1.1 ] vs 1.5 cm [ 0.9 ] , respectively ; P = .04 ) and were at more advanced stage ( regional/metastatic 25.4 % vs 16.0 % , respectively ; P = .04 ) compared with those diagnosed in the placebo group . After 1 year , the percentage of women with abnormal mammograms was substantially greater in the estrogen plus progestin group ( 716 [ 9.4 % ] of 7656 ) compared with placebo group ( 398 [ 5.4 % ] of 7310 ; P<.001 ) , a pattern which continued for the study duration . CONCLUSIONS Relatively short-term combined estrogen plus progestin use increases incident breast cancers , which are diagnosed at a more advanced stage compared with placebo use , and also substantially increases the percentage of women with abnormal mammograms . These results suggest estrogen plus progestin may stimulate breast cancer growth and hinder breast cancer diagnosis Background Although breast cancer risk is greater in users of estrogen – progestin than estrogen-only formulations of menopausal hormonal therapy  , reports on their effects have been somewhat inconsistent . We investigated whether the timing of these therapies affected breast cancer incidence . Methods A total of 1 129 025 postmenopausal UK women provided prospect i ve information on hormonal therapy use and other factors relevant for breast cancer risk . We used Cox regression to estimate adjusted relative risks ( RRs ) of breast cancer in hormonal therapy  users vs never users and calculated st and ardized incidence rates . All statistical tests were two-sided . Results During 4.05 million woman-years of follow-up , 15 759 incident breast cancers occurred , with 7107 in current users of hormonal therapy .  Breast cancer incidence was increased in current users of hormonal therapy , returning to that of never users a few years after use had ceased . The relative risks for breast cancer in current users were greater if hormonal therapy was begun before or soon after menopause than after a longer gap ( Pheterogeneity < .001 , for both estrogen-only and estrogen-progestin formulations ) . Among current users of estrogen-only formulations , there was little or no increase in risk if use began 5 years or more after menopause ( RR = 1.05 , 95 % confidence interval [ CI ] = 0.89 to 1.24 ) , but risk was statistically significantly increased if use began before or less than 5 years after menopause ( RR = 1.43 , 95 % CI = 1.35 to 1.51 ) . A similar pattern was observed among current users of estrogen – progestin formulations ( RR = 1.53 , 95 % CI = 1.38 to 1.70 , and RR = 2.04 , 95 % CI = 1.95 to 2.14 , respectively ) . At 50–59 years of age , annual st and ardized incidence rates for breast cancer were 0.30 % ( 95 % CI = 0.29 % to 0.31 % ) among never users of hormone therapy and 0.43 % ( 95 % CI = 0.42 % to 0.45 % ) and 0.61 % ( 95 % CI = 0.59 % to 0.64 % ) , respectively , among current users of estrogen-only and estrogen – progestin formulations who began use less than 5 years after menopause . Conclusions There was substantial heterogeneity in breast cancer risk among current users of hormonal therapy . Risks were greater among users of estrogen – progestin than estrogen-only formulations and if hormonal therapy started at around the time of menopause than later CONTEXT The Women 's Health Initiative Estrogen-Aone trial comparing conjugated equine estrogens ( CEE ) with placebo was stopped early because of an increased stroke incidence and no reduction in risk of coronary heart disease . Preliminary results suggesting possible reduction in breast cancers warranted more detailed analysis . OBJECTIVE To determine the effects of CEE on breast cancers and mammographic findings . DESIGN , SETTING , AND PARTICIPANTS Following breast cancer risk assessment , 10,739 postmenopausal women aged 50 to 79 years with prior hysterectomy were r and omized to CEE or placebo at 40 US clinical centers from 1993 through 1998 . Mammography screenings and clinical breast examinations were performed at baseline and annually . All breast cancers diagnosed through February 29 , 2004 , are included . INTERVENTION A dose of 0.625 mg/d of CEE or an identical-appearing placebo . MAIN OUTCOME MEASURES Breast cancer incidence , tumor characteristics , and mammogram findings . RESULTS After a mean ( SD ) follow-up of 7.1 ( 1.6 ) years , the invasive breast cancer hazard ratio ( HR ) for women assigned to CEE vs placebo was 0.80 ( 95 % confidence interval [ CI ] , 0.62 - 1.04 ; P = .09 ) with annualized rates of 0.28 % ( 104 cases in the CEE group ) and 0.34 % ( 133 cases in the placebo group ) . In exploratory analyses , ductal carcinomas ( HR , 0.71 ; 95 % CI , 0.52 - 0.99 ) were reduced in the CEE group vs placebo group ; however , the test for interaction by tumor type was not significant ( P = .054 ) . At 1 year , 9.2 % of women in the CEE group had mammograms with abnormalities requiring follow-up vs 5.5 % in the placebo group ( P<.001 ) , a pattern that continued through the trial to reach a cumulative percentage of 36.2 % vs 28.1 % , respectively ( P<.001 ) ; however , this difference was primarily in assessment s requiring short interval follow-up . CONCLUSIONS Treatment with CEE alone for 7.1 years does not increase breast cancer incidence in postmenopausal women with prior hysterectomy . However , treatment with CEE increases the frequency of mammography screening requiring short interval follow-up . Initiation of CEE should be based on consideration of the individual woman 's potential risks and benefits . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000611 The authors further analyzed results from the Women 's Health Initiative r and omized trials ( 1993 - 2004 ) of conjugated equine estrogens , with or without medroxyprogesterone acetate , focusing on health benefits versus risks among women who initiated hormone therapy soon after menopause . Data from the Women 's Health Initiative observational study ( 1993 - 2004 ) were included in some analyses for additional precision . Results are presented here for incident coronary heart disease , stroke , venous thromboembolism , breast cancer , colorectal cancer , endometrial cancer , or hip fracture ; death from other causes ; a summary global index ; total cancer ; and total mortality . Hazard ratios for breast cancer and total cancer were comparatively higher ( P < 0.05 ) among women who initiated hormone therapy soon after menopause , for both regimens . Among these women , use of conjugated equine estrogens appeared to produce elevations in venous thromboembolism and stroke and a reduction in hip fracture .  Estrogen plus progestin results among women who initiated use soon after menopause were similar for venous thromboembolism , stroke , and hip fracture but also included evidence of longer-term elevations in breast cancer , total cancer , and the global index . These analyses provide little support for the hypothesis of favorable effects among women who initiate postmenopausal estrogen use soon after menopause , either for coronary heart disease or for health benefits versus risk indices considered BACKGROUND Observational studies examining the role of estrogen in the risk of kidney stone formation have shown conflicting results . However , r and omized trial evidence on nephrolithiasis risk with  estrogen therapy in postmenopausal women is lacking . METHODS We review ed the incidence of nephrolithiasis in the Women 's Health Initiative estrogen-alone and estrogen plus progestin trials conducted at 40 US clinical centers . A total of 10 739 postmenopausal women with hysterectomy were r and omized to receive 0.625 mg/d of conjugated equine estrogens ( CEE ) or placebo , and 16 608 postmenopausal women without hysterectomy were r and omized to receive placebo or estrogen plus progestin given as CEE plus medroxyprogesterone acetate ( 2.5 mg/d ) . The incidence of nephrolithiasis was determined for an average follow-up of 7.1 years for the CEE trial and 5.6 years for the estrogen plus progestin trial . RESULTS Baseline demographic characteristics and risk factors for nephrolithiasis were similar in the placebo and treatment arms . Estrogen therapy was associated with a significant increase in nephrolithiasis risk from 34 to 39 cases per 10 000 person-years ( hazard ratio , 1.21 ; 95 % confidence interval , 1.03 - 1.44 ) . Censoring data from women when they ceased to adhere to study medication increased the hazard ratio to 1.39 ( 95 % confidence interval , 1.08 - 1.78 ) . The increased nephrolithiasis risk was independent of progestin coadministration , and effects did not vary significantly according to prer and omization history of nephrolithiasis . CONCLUSIONS These data suggest that estrogen therapy increases the risk of nephrolithiasis  in healthy postmenopausal women . These findings should be considered in decision making regarding postmenopausal estrogen use . The mechanisms underlying this higher susceptibility remain to be determined . Trial Registration clinical trials.gov Identifier : NCT0000611 OBJECTIVES To determine whether small decrements in global cognitive function that conjugated equine estro 
    Output:
    
agent
In relatively healthy women , combined continuous HT significantly increased the risk of venous thrombo-embolism or coronary event ( after one year 's use ) , stroke ( after three years ) , breast cancer and gallbladder disease .
Long-term oestrogen-only HT significantly increased the risk of venous thrombo-embolism , stroke and gallbladder disease ( after one to two years , three years and seven years ' use respectively ) , but did not significantly increase the risk of breast cancer .
The only statistically significant benefits of HT were a decreased incidence of fractures and ( for combined HT ) colon cancer , with long-term use .
Among women aged over 65 who were relatively healthy ( i.e. generally fit , without overt disease ) and taking continuous combined HT , there was a statistically significant increase in the incidence of dementia .
Among women with cardiovascular disease , long-term use of combined continuous HT significantly increased the risk of venous thrombo-embolism .
AUTHORS ' CONCLUSIONS HT is not indicated for the routine management of chronic disease .
We need more evidence on the safety of HT for menopausal symptom control , though short-term use appears to be relatively safe for healthy younger women
***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: 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 CONTEXT The Women 's Health Initiative trial of combined estrogen plus progestin was stopped early when overall health risks , including invasive breast cancer , exceeded benefits . Outst and ing issues not previously addressed include characteristics of breast cancers observed among women using hormones and whether diagnosis may be influenced by hormone effects on mammography . OBJECTIVE To determine the relationship among estrogen plus progestin use , breast cancer characteristics , and mammography recommendations . DESIGN , SETTING , AND PARTICIPANTS Following a comprehensive breast cancer risk assessment , 16 608 postmenopausal women aged 50 to 79 years with an intact uterus were r and omly assigned to receive combined conjugated equine estrogens ( 0.625 mg/d ) plus medroxyprogesterone acetate ( 2.5 mg/d ) or placebo from 1993 to 1998 at 40 clinical centers . Screening mammography and clinical breast examinations were performed at baseline and yearly thereafter . MAIN OUTCOME MEASURES Breast cancer number and characteristics , and frequency of abnormal mammograms by estrogen plus progestin exposure . RESULTS In intent-to-treat analyses , estrogen plus progestin increased total ( 245 vs 185 cases ; hazard ratio [ HR ] , 1.24 ; weighted P<.001 ) and invasive ( 199 vs 150 cases ; HR , 1.24 ; weighted P = .003 ) breast cancers compared with placebo . The invasive breast cancers diagnosed in the estrogen plus progestin group were similar in histology and grade but were larger ( mean [ SD ] , 1.7 cm [ 1.1 ] vs 1.5 cm [ 0.9 ] , respectively ; P = .04 ) and were at more advanced stage ( regional/metastatic 25.4 % vs 16.0 % , respectively ; P = .04 ) compared with those diagnosed in the placebo group . After 1 year , the percentage of women with abnormal mammograms was substantially greater in the estrogen plus progestin group ( 716 [ 9.4 % ] of 7656 ) compared with placebo group ( 398 [ 5.4 % ] of 7310 ; P<.001 ) , a pattern which continued for the study duration . CONCLUSIONS Relatively short-term combined estrogen plus progestin use increases incident breast cancers , which are diagnosed at a more advanced stage compared with placebo use , and also substantially increases the percentage of women with abnormal mammograms . These results suggest estrogen plus progestin may stimulate breast cancer growth and hinder breast cancer diagnosis Background Although breast cancer risk is greater in users of estrogen – progestin than estrogen-only formulations of menopausal hormonal therapy  , reports on their effects have been somewhat inconsistent . We investigated whether the timing of these therapies affected breast cancer incidence . Methods A total of 1 129 025 postmenopausal UK women provided prospect i ve information on hormonal therapy use and other factors relevant for breast cancer risk . We used Cox regression to estimate adjusted relative risks ( RRs ) of breast cancer in hormonal therapy  users vs never users and calculated st and ardized incidence rates . All statistical tests were two-sided . Results During 4.05 million woman-years of follow-up , 15 759 incident breast cancers occurred , with 7107 in current users of hormonal therapy .  Breast cancer incidence was increased in current users of hormonal therapy , returning to that of never users a few years after use had ceased . The relative risks for breast cancer in current users were greater if hormonal therapy was begun before or soon after menopause than after a longer gap ( Pheterogeneity < .001 , for both estrogen-only and estrogen-progestin formulations ) . Among current users of estrogen-only formulations , there was little or no increase in risk if use began 5 years or more after menopause ( RR = 1.05 , 95 % confidence interval [ CI ] = 0.89 to 1.24 ) , but risk was statistically significantly increased if use began before or less than 5 years after menopause ( RR = 1.43 , 95 % CI = 1.35 to 1.51 ) . A similar pattern was observed among current users of estrogen – progestin formulations ( RR = 1.53 , 95 % CI = 1.38 to 1.70 , and RR = 2.04 , 95 % CI = 1.95 to 2.14 , respectively ) . At 50–59 years of age , annual st and ardized incidence rates for breast cancer were 0.30 % ( 95 % CI = 0.29 % to 0.31 % ) among never users of hormone therapy and 0.43 % ( 95 % CI = 0.42 % to 0.45 % ) and 0.61 % ( 95 % CI = 0.59 % to 0.64 % ) , respectively , among current users of estrogen-only and estrogen – progestin formulations who began use less than 5 years after menopause . Conclusions There was substantial heterogeneity in breast cancer risk among current users of hormonal therapy . Risks were greater among users of estrogen – progestin than estrogen-only formulations and if hormonal therapy started at around the time of menopause than later CONTEXT The Women 's Health Initiative Estrogen-Aone trial comparing conjugated equine estrogens ( CEE ) with placebo was stopped early because of an increased stroke incidence and no reduction in risk of coronary heart disease . Preliminary results suggesting possible reduction in breast cancers warranted more detailed analysis . OBJECTIVE To determine the effects of CEE on breast cancers and mammographic findings . DESIGN , SETTING , AND PARTICIPANTS Following breast cancer risk assessment , 10,739 postmenopausal women aged 50 to 79 years with prior hysterectomy were r and omized to CEE or placebo at 40 US clinical centers from 1993 through 1998 . Mammography screenings and clinical breast examinations were performed at baseline and annually . All breast cancers diagnosed through February 29 , 2004 , are included . INTERVENTION A dose of 0.625 mg/d of CEE or an identical-appearing placebo . MAIN OUTCOME MEASURES Breast cancer incidence , tumor characteristics , and mammogram findings . RESULTS After a mean ( SD ) follow-up of 7.1 ( 1.6 ) years , the invasive breast cancer hazard ratio ( HR ) for women assigned to CEE vs placebo was 0.80 ( 95 % confidence interval [ CI ] , 0.62 - 1.04 ; P = .09 ) with annualized rates of 0.28 % ( 104 cases in the CEE group ) and 0.34 % ( 133 cases in the placebo group ) . In exploratory analyses , ductal carcinomas ( HR , 0.71 ; 95 % CI , 0.52 - 0.99 ) were reduced in the CEE group vs placebo group ; however , the test for interaction by tumor type was not significant ( P = .054 ) . At 1 year , 9.2 % of women in the CEE group had mammograms with abnormalities requiring follow-up vs 5.5 % in the placebo group ( P<.001 ) , a pattern that continued through the trial to reach a cumulative percentage of 36.2 % vs 28.1 % , respectively ( P<.001 ) ; however , this difference was primarily in assessment s requiring short interval follow-up . CONCLUSIONS Treatment with CEE alone for 7.1 years does not increase breast cancer incidence in postmenopausal women with prior hysterectomy . However , treatment with CEE increases the frequency of mammography screening requiring short interval follow-up . Initiation of CEE should be based on consideration of the individual woman 's potential risks and benefits . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000611 The authors further analyzed results from the Women 's Health Initiative r and omized trials ( 1993 - 2004 ) of conjugated equine estrogens , with or without medroxyprogesterone acetate , focusing on health benefits versus risks among women who initiated hormone therapy soon after menopause . Data from the Women 's Health Initiative observational study ( 1993 - 2004 ) were included in some analyses for additional precision . Results are presented here for incident coronary heart disease , stroke , venous thromboembolism , breast cancer , colorectal cancer , endometrial cancer , or hip fracture ; death from other causes ; a summary global index ; total cancer ; and total mortality . Hazard ratios for breast cancer and total cancer were comparatively higher ( P < 0.05 ) among women who initiated hormone therapy soon after menopause , for both regimens . Among these women , use of conjugated equine estrogens appeared to produce elevations in venous thromboembolism and stroke and a reduction in hip fracture .  Estrogen plus progestin results among women who initiated use soon after menopause were similar for venous thromboembolism , stroke , and hip fracture but also included evidence of longer-term elevations in breast cancer , total cancer , and the global index . These analyses provide little support for the hypothesis of favorable effects among women who initiate postmenopausal estrogen use soon after menopause , either for coronary heart disease or for health benefits versus risk indices considered BACKGROUND Observational studies examining the role of estrogen in the risk of kidney stone formation have shown conflicting results . However , r and omized trial evidence on nephrolithiasis risk with  estrogen therapy in postmenopausal women is lacking . METHODS We review ed the incidence of nephrolithiasis in the Women 's Health Initiative estrogen-alone and estrogen plus progestin trials conducted at 40 US clinical centers . A total of 10 739 postmenopausal women with hysterectomy were r and omized to receive 0.625 mg/d of conjugated equine estrogens ( CEE ) or placebo , and 16 608 postmenopausal women without hysterectomy were r and omized to receive placebo or estrogen plus progestin given as CEE plus medroxyprogesterone acetate ( 2.5 mg/d ) . The incidence of nephrolithiasis was determined for an average follow-up of 7.1 years for the CEE trial and 5.6 years for the estrogen plus progestin trial . RESULTS Baseline demographic characteristics and risk factors for nephrolithiasis were similar in the placebo and treatment arms . Estrogen therapy was associated with a significant increase in nephrolithiasis risk from 34 to 39 cases per 10 000 person-years ( hazard ratio , 1.21 ; 95 % confidence interval , 1.03 - 1.44 ) . Censoring data from women when they ceased to adhere to study medication increased the hazard ratio to 1.39 ( 95 % confidence interval , 1.08 - 1.78 ) . The increased nephrolithiasis risk was independent of progestin coadministration , and effects did not vary significantly according to prer and omization history of nephrolithiasis . CONCLUSIONS These data suggest that estrogen therapy increases the risk of nephrolithiasis  in healthy postmenopausal women . These findings should be considered in decision making regarding postmenopausal estrogen use . The mechanisms underlying this higher susceptibility remain to be determined . Trial Registration clinical trials.gov Identifier : NCT0000611 OBJECTIVES To determine whether small decrements in global cognitive function that conjugated equine estro 
    Output:
    