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: The effect of oral oestriol ( 3 mg/day for 4 weeks followed by 2 mg/day for a further 6 weeks ) on the vaginal bacterial flora , vaginal cytology and urogenital symptoms was assessed in a double-blind , placebo-controlled study in 35 women with symptoms of the urogenital oestrogen deficiency syndrome . No significant differences were observed with regard to the occurrence or severity of urogenital symptoms , vaginal pH , karyopyknotic index ( KPI ) or the baseline results of vaginal bacterial cultures in the 18 patients ( mean age 71.6 + /- 1.0 years ) treated with oestriol and the 17 women ( mean age 72.6 + /- 1.4 years ) who received placebo tablets . A decrease in both vaginal pH ( P less than 0.001 ) and the proportion of faecal-type bacteria ( P less than 0.05 ) , and an increase in the KPI ( P less than 0.01 ) and the proportion of lactobacilli ( P less than 0.001 ) were recorded after 10 weeks of treatment with oral oestriol . At the end of the following 10 medication-free weeks all of these parameters except vaginal pH had returned to values that were not significantly altered from the corresponding baseline levels . In the patients treated with placebo no significant changes occurred in vaginal pH , KPI or the proportion of lactobacilli in vaginal cultures during the course of this study . Urogenital symptoms improved in both groups after medication ( and even after the medication-free period ) in relation to the baseline assessment , which reflects the latter 's subjective nature Objective —The effects of hormone replacement therapy ( HRT ) can affect many aspects relevant to cardiovascular disease , including vasomotor function , inflammation , and hemostasis . Recent studies have demonstrated that current doses of HRT exert a mixture of both protective and adverse effects . In the current study , we compared the effects of lower doses of HRT ( L-HRT ) and conventional doses of HRT ( C-HRT ) on a variety of relevant cardiovascular parameters . Methods and Results —This r and omized , double-blind , crossover study included 57 women who received micronized progesterone 100 mg with either conjugated equine estrogen 0.625 mg ( C-HRT ) or 0.3 mg ( L-HRT ) daily for 2 months .  L-HRT showed comparable effects to C-HRT on high-density lipoprotein cholesterol and triglyceride levels , but not on low-density lipoprotein cholesterol levels .  C-HRT and L-HRT significantly improved the percent flow-mediated dilator response to hyperemia from baseline values ( both P < 0.001 ) by a similar degree ( P = 0.719 ) . C-HRT significantly increased high-sensitivity C-reactive protein ( hsCRP ) levels from baseline values ( P < 0.001 ) ; however , L-HRT did not significantly change hsCRP ( P = 0.874 ) . C-HRT and L-HRT significantly decreased antithrombin III from baseline values ( P < 0.001 and P = 0.042 , respectively ) . C-HRT significantly increased prothrombin fragment 1 + 2 ( F1 + 2 ) from baseline values ( P < 0.001 ) ; however , L-HRT did not significantly change F1 + 2 ( P = 0.558 ) . Of interest , the effects of C-HRT and L-HRT on hsCRP , antithrombin III , and F1 + 2 were significantly different ( all P < 0.001 ) . C-HRT and L-HRT significantly reduced plasma PAI-1 antigen levels from baseline values ( P = 0.002 and P = 0.038 , respectively ) to a similar degree ( P = 0.184 ) . Conclusions —Compared with C-HRT , L-HRT has comparable effects on lipoproteins , flow-mediated dilation , and PAI-1 antigen levels . However , L-HRT did not increase hsCRP or F1 + 2 levels , and it decreased antithrombin III less than C-HRT Background and Purpose — Raloxifene , a selective estrogen receptor modulator , reduces risk of invasive breast cancer and osteoporosis , but the effect on risk for stroke and venous thromboembolism in different patient subgroups is not established . The purpose of this analysis was to evaluate the effect of raloxifene on the incidence of all strokes , stroke deaths , and venous thromboembolic events according to participant subgroups . Methods — This was a secondary end point analysis of an international , r and omized , placebo-controlled clinical trial of 10 101 postmenopausal women with or at increased risk of coronary heart disease followed a median of 5.6 years .  Strokes , venous thromboembolic events , and deaths were adjudicated by expert central ized committees . Strokes were categorized as ischemic , hemorrhagic , or undetermined and venous thromboembolic events were subclassified . Results — The incidences of all strokes did not differ between raloxifene ( incidence rate per 100 woman-years=0.95 ) and placebo ( incidence rate=0.86 ) treatment groups ( P=0.30 ) . In women assigned raloxifene versus placebo , there was a higher incidence of fatal strokes ( incidence rates=0.22 and 0.15 , respectively , P=0.0499 ) and venous thromboembolic events ( incidence rates=0.39 and 0.27 , respectively , P=0.02 ) . No significant subgroup interactions were found except that there was a higher incidence of stroke associated with raloxifene use among current smokers . Conclusions — In postmenopausal women at increased risk for coronary events , the incidences of venous thromboembolism and fatal stroke but not all strokes were higher in those assigned raloxifene versus placebo . Raloxifene ’s effect did not differ across subgroups , except that the risk of stroke differed by smoking status . Treatment decisions about raloxifene should be based on a balance of projected absolute risks and benefits 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 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 study was to determine whether HRT can slow progression of atherosclerosis , measured as intima-media thickness ( IMT ) in carotid arteries . Carotid IMT is an appropriate intermediate end point to investigate clinical ly relevant effects on atherogenesis . This r and omized , controlled , observer-blind , clinical , single-center trial enrolled 321 healthy postmenopausal women with increased IMT in ≥1 segment of the carotid arteries . For a period of 48 weeks , subjects received either 1 mg/d 17&bgr;-estradiol continuously plus 0.025 mg gestodene for 12 days every month ( st and ard-progestin group ) , or 1 mg 17&bgr;-estradiol plus 0.025 mg gestodene for 12 days every third month ( low-progestin group ) , or no HRT . Maximum IMT in 6 carotid artery segments ( common , bifurcation , and internal , both sides ) was measured by B-mode ultrasound before and after intervention . HRT  did not slow IMT progression in carotid arteries . Mean maximum IMT in the carotid arteries increased by 0.02±0.05 mm in the no HRT group and by 0.03±0.05 and 0.03±0.05 mm , respectively , in the HRT groups ( P > 0.2 ) . HRT  significantly decreased LDL cholesterol , fibrinogen , and follicle-stimulating hormone . In conclusion , 1 year of HRT was not effective in slowing progression of sub clinical atherosclerosis in postmenopausal women at increased risk Objective To assess the effect of  combined hormone replacement therapy ( HRT )  on health related quality of life . Design R and omised placebo controlled double blind trial . Setting General practice s in United Kingdom ( 384 ) , Australia ( 94 ) , and New Zeal and ( 24 ) . Participants Postmenopausal women aged 50 - 69 at r and omisation ; 3721 women with a uterus were r and omised to combined oestrogen and progestogen  ( n=1862 ) or placebo  ( n=1859 ) . Data on health related quality of life at one year were available from 1043 and 1087 women , respectively . Interventions Conjugated equine oestrogen 0.625 mg plus medroxyprogesterone acetate 2.5/5.0 mg or matched placebo orally daily for one year . Main outcome measures Health related quality of life and psychological wellbeing as measured by the women ’s health question naire . Changes in emotional and physical menopausal symptoms as measured by a symptoms question naire and depression by the Centre for Epidemiological Studies depression scale ( CES-D ) . Overall health related quality of life and overall quality of life as measured by the European quality of life instrument ( EuroQol ) and visual analogue scale , respectively . Results After one year small but significant improvements were observed in three of nine components of the women ’s health question naire for those taking combined HRT compared with those taking placebo :  vasomotor symptoms ( P<0.001 ) , sexual functioning ( P<0.001 ) , and sleep problems ( P<0.001 ) . Significantly fewer women in the combined HRT group reported hot flushes ( P<0.001 ) , night sweats ( P<0.001 ) , aching joints and muscles ( P=0.001 ) , insomnia ( P<0.001 ) , and vaginal dryness ( P<0.001 ) than in the placebo group , but greater proportions reported breast tenderness ( P<0.001 ) or vaginal discharge ( P<0.001 ) . Hot flushes were experienced in the combined HRT and placebo groups by 30 % and 29 % at trial entry and 9 % and 25 % at one year , respectively . No significant differences in other menopausal symptoms , depression , or overall quality of life were observed at one year . Conclusions Combined HRT started many years after the menopause can improve health related quality of life . Trial registration IS RCT N 63718836 Estrogen deficiency and declining calcium absorption due to reduced calcitriol levels or intestinal resistance to calcitriol , are important factors in the pathogenesis of age-related bone loss . The main objective of this study was to examine the effect of estrogen and 1,25-dihydroxyvitamin D therapy given individually or in combination on  bone loss in elderly women . Four hundred eighty-nine elderly women with normal bone density for their age , aged 65 - 77 yr , were entered into a r and omized double blind , placebo-controlled trial . Women were r and omized to one of four groups : conjugated estrogens ( 0.625 mg , daily ) to women without a uterus ( estrogen replacement therapy ) plus medroxyprogesterone acetate ( 2.5 mg , daily ) to women with a uterus ( hormone replacement therapy ) , calcitriol ( 0.25 microg twice daily ) , a combination of hormone replacement therapy/estrogen replacement therapy plus calcitriol , or placebos for 3 y 
    Output:
    
agent
We found high quality evidence that hormone therapy in both primary and secondary prevention conferred no protective effects for all-cause mortality , cardiovascular death , non-fatal myocardial infa rct ion , angina , or revascularisation .
There was no strong evidence of effect on risk of stroke in this group .
Our review findings provide strong evidence that treatment with hormone therapy in post-menopausal women overall , for either primary or secondary prevention of cardiovascular disease events has little if any benefit and causes an increase in the risk of stroke and venous thromboembolic events
***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: The effect of oral oestriol ( 3 mg/day for 4 weeks followed by 2 mg/day for a further 6 weeks ) on the vaginal bacterial flora , vaginal cytology and urogenital symptoms was assessed in a double-blind , placebo-controlled study in 35 women with symptoms of the urogenital oestrogen deficiency syndrome . No significant differences were observed with regard to the occurrence or severity of urogenital symptoms , vaginal pH , karyopyknotic index ( KPI ) or the baseline results of vaginal bacterial cultures in the 18 patients ( mean age 71.6 + /- 1.0 years ) treated with oestriol and the 17 women ( mean age 72.6 + /- 1.4 years ) who received placebo tablets . A decrease in both vaginal pH ( P less than 0.001 ) and the proportion of faecal-type bacteria ( P less than 0.05 ) , and an increase in the KPI ( P less than 0.01 ) and the proportion of lactobacilli ( P less than 0.001 ) were recorded after 10 weeks of treatment with oral oestriol . At the end of the following 10 medication-free weeks all of these parameters except vaginal pH had returned to values that were not significantly altered from the corresponding baseline levels . In the patients treated with placebo no significant changes occurred in vaginal pH , KPI or the proportion of lactobacilli in vaginal cultures during the course of this study . Urogenital symptoms improved in both groups after medication ( and even after the medication-free period ) in relation to the baseline assessment , which reflects the latter 's subjective nature Objective —The effects of hormone replacement therapy ( HRT ) can affect many aspects relevant to cardiovascular disease , including vasomotor function , inflammation , and hemostasis . Recent studies have demonstrated that current doses of HRT exert a mixture of both protective and adverse effects . In the current study , we compared the effects of lower doses of HRT ( L-HRT ) and conventional doses of HRT ( C-HRT ) on a variety of relevant cardiovascular parameters . Methods and Results —This r and omized , double-blind , crossover study included 57 women who received micronized progesterone 100 mg with either conjugated equine estrogen 0.625 mg ( C-HRT ) or 0.3 mg ( L-HRT ) daily for 2 months .  L-HRT showed comparable effects to C-HRT on high-density lipoprotein cholesterol and triglyceride levels , but not on low-density lipoprotein cholesterol levels .  C-HRT and L-HRT significantly improved the percent flow-mediated dilator response to hyperemia from baseline values ( both P < 0.001 ) by a similar degree ( P = 0.719 ) . C-HRT significantly increased high-sensitivity C-reactive protein ( hsCRP ) levels from baseline values ( P < 0.001 ) ; however , L-HRT did not significantly change hsCRP ( P = 0.874 ) . C-HRT and L-HRT significantly decreased antithrombin III from baseline values ( P < 0.001 and P = 0.042 , respectively ) . C-HRT significantly increased prothrombin fragment 1 + 2 ( F1 + 2 ) from baseline values ( P < 0.001 ) ; however , L-HRT did not significantly change F1 + 2 ( P = 0.558 ) . Of interest , the effects of C-HRT and L-HRT on hsCRP , antithrombin III , and F1 + 2 were significantly different ( all P < 0.001 ) . C-HRT and L-HRT significantly reduced plasma PAI-1 antigen levels from baseline values ( P = 0.002 and P = 0.038 , respectively ) to a similar degree ( P = 0.184 ) . Conclusions —Compared with C-HRT , L-HRT has comparable effects on lipoproteins , flow-mediated dilation , and PAI-1 antigen levels . However , L-HRT did not increase hsCRP or F1 + 2 levels , and it decreased antithrombin III less than C-HRT Background and Purpose — Raloxifene , a selective estrogen receptor modulator , reduces risk of invasive breast cancer and osteoporosis , but the effect on risk for stroke and venous thromboembolism in different patient subgroups is not established . The purpose of this analysis was to evaluate the effect of raloxifene on the incidence of all strokes , stroke deaths , and venous thromboembolic events according to participant subgroups . Methods — This was a secondary end point analysis of an international , r and omized , placebo-controlled clinical trial of 10 101 postmenopausal women with or at increased risk of coronary heart disease followed a median of 5.6 years .  Strokes , venous thromboembolic events , and deaths were adjudicated by expert central ized committees . Strokes were categorized as ischemic , hemorrhagic , or undetermined and venous thromboembolic events were subclassified . Results — The incidences of all strokes did not differ between raloxifene ( incidence rate per 100 woman-years=0.95 ) and placebo ( incidence rate=0.86 ) treatment groups ( P=0.30 ) . In women assigned raloxifene versus placebo , there was a higher incidence of fatal strokes ( incidence rates=0.22 and 0.15 , respectively , P=0.0499 ) and venous thromboembolic events ( incidence rates=0.39 and 0.27 , respectively , P=0.02 ) . No significant subgroup interactions were found except that there was a higher incidence of stroke associated with raloxifene use among current smokers . Conclusions — In postmenopausal women at increased risk for coronary events , the incidences of venous thromboembolism and fatal stroke but not all strokes were higher in those assigned raloxifene versus placebo . Raloxifene ’s effect did not differ across subgroups , except that the risk of stroke differed by smoking status . Treatment decisions about raloxifene should be based on a balance of projected absolute risks and benefits 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 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 study was to determine whether HRT can slow progression of atherosclerosis , measured as intima-media thickness ( IMT ) in carotid arteries . Carotid IMT is an appropriate intermediate end point to investigate clinical ly relevant effects on atherogenesis . This r and omized , controlled , observer-blind , clinical , single-center trial enrolled 321 healthy postmenopausal women with increased IMT in ≥1 segment of the carotid arteries . For a period of 48 weeks , subjects received either 1 mg/d 17&bgr;-estradiol continuously plus 0.025 mg gestodene for 12 days every month ( st and ard-progestin group ) , or 1 mg 17&bgr;-estradiol plus 0.025 mg gestodene for 12 days every third month ( low-progestin group ) , or no HRT . Maximum IMT in 6 carotid artery segments ( common , bifurcation , and internal , both sides ) was measured by B-mode ultrasound before and after intervention . HRT  did not slow IMT progression in carotid arteries . Mean maximum IMT in the carotid arteries increased by 0.02±0.05 mm in the no HRT group and by 0.03±0.05 and 0.03±0.05 mm , respectively , in the HRT groups ( P > 0.2 ) . HRT  significantly decreased LDL cholesterol , fibrinogen , and follicle-stimulating hormone . In conclusion , 1 year of HRT was not effective in slowing progression of sub clinical atherosclerosis in postmenopausal women at increased risk Objective To assess the effect of  combined hormone replacement therapy ( HRT )  on health related quality of life . Design R and omised placebo controlled double blind trial . Setting General practice s in United Kingdom ( 384 ) , Australia ( 94 ) , and New Zeal and ( 24 ) . Participants Postmenopausal women aged 50 - 69 at r and omisation ; 3721 women with a uterus were r and omised to combined oestrogen and progestogen  ( n=1862 ) or placebo  ( n=1859 ) . Data on health related quality of life at one year were available from 1043 and 1087 women , respectively . Interventions Conjugated equine oestrogen 0.625 mg plus medroxyprogesterone acetate 2.5/5.0 mg or matched placebo orally daily for one year . Main outcome measures Health related quality of life and psychological wellbeing as measured by the women ’s health question naire . Changes in emotional and physical menopausal symptoms as measured by a symptoms question naire and depression by the Centre for Epidemiological Studies depression scale ( CES-D ) . Overall health related quality of life and overall quality of life as measured by the European quality of life instrument ( EuroQol ) and visual analogue scale , respectively . Results After one year small but significant improvements were observed in three of nine components of the women ’s health question naire for those taking combined HRT compared with those taking placebo :  vasomotor symptoms ( P<0.001 ) , sexual functioning ( P<0.001 ) , and sleep problems ( P<0.001 ) . Significantly fewer women in the combined HRT group reported hot flushes ( P<0.001 ) , night sweats ( P<0.001 ) , aching joints and muscles ( P=0.001 ) , insomnia ( P<0.001 ) , and vaginal dryness ( P<0.001 ) than in the placebo group , but greater proportions reported breast tenderness ( P<0.001 ) or vaginal discharge ( P<0.001 ) . Hot flushes were experienced in the combined HRT and placebo groups by 30 % and 29 % at trial entry and 9 % and 25 % at one year , respectively . No significant differences in other menopausal symptoms , depression , or overall quality of life were observed at one year . Conclusions Combined HRT started many years after the menopause can improve health related quality of life . Trial registration IS RCT N 63718836 Estrogen deficiency and declining calcium absorption due to reduced calcitriol levels or intestinal resistance to calcitriol , are important factors in the pathogenesis of age-related bone loss . The main objective of this study was to examine the effect of estrogen and 1,25-dihydroxyvitamin D therapy given individually or in combination on  bone loss in elderly women . Four hundred eighty-nine elderly women with normal bone density for their age , aged 65 - 77 yr , were entered into a r and omized double blind , placebo-controlled trial . Women were r and omized to one of four groups : conjugated estrogens ( 0.625 mg , daily ) to women without a uterus ( estrogen replacement therapy ) plus medroxyprogesterone acetate ( 2.5 mg , daily ) to women with a uterus ( hormone replacement therapy ) , calcitriol ( 0.25 microg twice daily ) , a combination of hormone replacement therapy/estrogen replacement therapy plus calcitriol , or placebos for 3 y 
    Output:
    