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: CONTEXT Lower circulating testosterone concentrations are associated with metabolic syndrome , type 2 diabetes , carotid intima-media thickness , and aortic and lower limb arterial disease in men . However , it is unclear whether lower testosterone levels predict major cardiovascular events . OBJECTIVE We examined whether lower serum testosterone was an independently significant risk factor for symptomatic cerebrovascular events  in older men . DESIGN This was a prospect i ve observational study with median follow-up of 3.5 yr . SETTING Community-dwelling , stroke-free older men were studied . PARTICIPANTS A total of 3443 men at least 70 yr of age participated in the study . MAIN OUTCOME MEASURES  Baseline serum total testosterone , SHBG , and LH were assayed . Free testosterone  was calculated using mass action equations . Incident stroke or transient ischemic attack ( TIA ) was recorded . RESULTS A first stroke or TIA occurred in 119 men ( 3.5 % ) .  Total and free testosterone concentrations in the lowest quartiles ( < 11.7 nmol/liter and < 222 pmol/liter ) were associated with reduced event-free survival ( P = 0.014 and P = 0.01 , respectively ) . After adjustment including age , waist-hip ratio , waist circumference , smoking , hypertension , dyslipidemia , and medical comorbidity , lower total testosterone predicted increased incidence of stroke or TIA ( hazard ratio = 1.99 ; 95 % confidence interval , 1.33 - 2.99 ) . Lower free testosterone was also associated ( hazard ratio = 1.69 ; 95 % confidence interval , 1.15 - 2.48 ) , whereas SHBG and LH were not independently associated with incident stroke or TIA . CONCLUSIONS In older men , lower total testosterone levels predict increased incidence of stroke or TIA after adjusting for conventional risk factors for cardiovascular disease . Men with low-normal testosterone levels had increased risk . Further studies are warranted to determine whether interventions that raise circulating testosterone levels might prevent cerebrovascular disease in men CONTEXT Declining testosterone levels in elderly men are thought to underlie many of the symptoms and diseases of aging ; however , studies demonstrating associations of low testosterone with clinical outcomes are few . OBJECTIVE The objective of the study was to examine the association of endogenous testosterone levels with mortality in older community-dwelling men . DESIGN , SETTING , AND PARTICIPANTS This was a prospect i ve , population -based study of 794 men , aged 50 - 91 ( median 73.6 ) yr who had serum testosterone measurements at baseline ( 1984 - 1987 ) and were followed for mortality through July 2004 . MAIN OUTCOME MEASURE All-cause mortality by serum testosterone level  was measured . RESULTS During an average 11.8-yr follow-up , 538 deaths occurred . Men whose total testosterone levels were in the lowest quartile ( < 241 ng/dl ) were 40 % [ hazards ratio ( HR ) 1.40 ; 95 % confidence interval ( CI ) 1.14 - 1.71 ] more likely to die than those with higher levels , independent of age , adiposity , and lifestyle . Additional adjustment for health status markers , lipids , lipoproteins , blood pressure , glycemia , adipocytokines , and estradiol levels had minimal effect on results . The low testosterone-mortality association was also independent of the metabolic syndrome , diabetes , and prevalent cardiovascular disease but was attenuated by adjustment for IL-6 and C-reactive protein . In cause-specific analyses , low testosterone predicted increased risk of cardiovascular ( HR 1.38 ; 95 % CI 1.02 - 1.85 ) and respiratory disease ( HR 2.29 ; 95 % CI 1.25 - 4.20 ) mortality but was not significantly related to cancer death ( HR 1.34 ; 95 % CI 0.89 - 2.00 ) . Results were similar for bioavailable testosterone . CONCLUSIONS Testosterone insufficiency in older men is associated with increased risk of death over the following 20 yr , independent of multiple risk factors and several preexisting health conditions BACKGROUND Low serum testosterone is a common condition in aging associated with decreased muscle mass and insulin resistance . This study evaluated whether low testosterone levels are a risk factor for mortality in male veterans . METHODS We used a clinical data base to identify men older than 40 years with repeated testosterone levels obtained from October 1 , 1994 , to December 31 , 1999 , and without diagnosed prostate cancer . A low testosterone level was a total testosterone level of less than 250 ng/dL ( < 8.7 nmol/L ) or a free testosterone level of less than 0.75 ng/dL ( < 0.03 nmol/L ) . Men were classified as having a low testosterone level ( 166 [ 19.3 % ] ) , an equivocal testosterone level ( equal number of low and normal levels ) ( 240 [ 28.0 % ] ) , or a normal testosterone level ( 452 [ 52.7 % ] ) . The risk for all-cause mortality was estimated using Cox proportional hazards regression models , adjusting for demographic and clinical covariates over a follow-up of up to 8 years . RESULTS Mortality in men with normal testosterone levels was 20.1 % ( 95 % confidence interval [ CI ] , 16.2%-24.1 % ) vs 24.6 % ( 95 % CI , 19.2%-30.0 % ) in men with equivocal testosterone levels and 34.9 % ( 95 % CI , 28.5%-41.4 % ) in men with low testosterone levels . After adjusting for age , medical morbidity , and other clinical covariates , low testosterone levels continued to be associated with increased mortality ( hazard ratio , 1.88 ; 95 % CI , 1.34 - 2.63 ; P<.001 ) while equivocal testosterone levels were not significantly different from normal testosterone levels ( hazard ratio , 1.38 ; 95 % CI , 0.99%-1.92 % ; P=.06 ) . In a sensitivity analysis , men who died within the first year ( 50 [ 5.8 % ] ) were excluded to minimize the effect of acute illness , and low testosterone levels continued to be associated with elevated mortality . CONCLUSIONS Low testosterone levels were associated with increased mortality in male veterans . Further prospect i ve studies are needed to examine the association between low testosterone levels and mortality Background —There is a popular belief that chronic stress causes heart disease through psychoneuroendocrine mechanisms . We have examined whether an elevated circulating cortisol-to-testosterone ratio increases the risk of ischemic heart disease . Methods and Results —We undertook a prospect i ve cohort study of 2512 men aged 45 to 59 years between 1979 and 1983 from Caerphilly , South Wales , with a mean follow-up of 16.5 years . Subjects underwent a clinical examination , and morning fasting blood sample s were taken for analysis of cortisol levels , testosterone levels , and other cardiovascular risk factors . The ratio of cortisol to testosterone showed weak associations with potential confounding factors but strong positive associations with components of the insulin resistance syndrome ( P<0.001 ) . A positive linear trend was seen across quintiles of cortisol : testosterone ratio for incident ischemic heart disease ( age-adjusted OR per z score change in ratio 1.22 , 95 % CI 1.07 to 1.38 , P=0.003 ) . This was markedly attenuated after adjustment for components of the insulin resistance syndrome ( age-adjusted OR per z score change in ratio 1.10 , 95 % CI 0.96 to 1.25 , P=0.18 ) . There was no association between the cortisol : testosterone ratio and other causes of death ( age-adjusted hazard ratio 0.99 , 95 % CI 0.88 to 1.11 , P=0.81 ) . Conclusions —This is the first population -based prospect i ve study that has found a specific association between cortisol : testosterone ratio and incident ischemic heart disease , apparently mediated through the insulin resistance syndrome . Whether this reflects the effects of chronic stress , behavioral factors , or genetic influences remains to be determined CONTEXT Age-related reduction of serum testosterone may contribute to the signs and symptoms of aging , but previous studies report conflicting evidence about testosterone levels and male mortality . No large prospect i ve cohort study has determined a possible association between serum estradiol and mortality in men . OBJECTIVE The main objective was to examine the association between serum testosterone and estradiol and all-cause mortality  in elderly men . DESIGN , SETTING , AND PARTICIPANTS We used specific gas chromatography-mass spectrometry to analyze serum sex steroids at baseline in older men who participated in the prospect i ve population -based MrOS Sweden cohort ( n = 3014 ; mean age , 75 yr ; range , 69 - 80 yr ) . MAIN OUTCOME MEASURE All-cause mortality by serum testosterone and estradiol levels . RESULTS During a mean follow-up period of 4.5 yr , 383 deaths occurred . In multivariate hazards regression models , low levels ( within quartile 1 vs. quartiles 2 - 4 ) of both testosterone [ hazard ratio ( HR ) , 1.65 ; 95 % confidence interval ( CI ) , 1.29 - 2.12 ] and estradiol ( HR , 1.54 ; 95 % CI , 1.22 - 1.95 ) associated with mortality . A model including both hormones showed that both low testosterone ( HR , 1.46 ; 95 % CI , 1.11 - 1.92 ) and estradiol ( HR , 1.33 ; 95 % CI , 1.02 - 1.73 ) predicted mortality . Risk of death nearly doubled ( HR , 1.96 ; 95 % CI , 1.46 - 2.62 ) in subjects with low levels of both testosterone and estradiol compared with subjects within quartiles 2 - 4 of both hormones . CONCLUSIONS Elderly men with low serum testosterone and estradiol have increased risk of mortality , and subjects with low values of both testosterone and estradiol have the highest risk of mortality It has been hypothesized that hyperestrogenemia may underlie myocardial infa rct ion . As a test of this hypothesis , the serum estradiol and testosterone levels were estimated in sample s collected prospect ively from 96 male patients aged 52 - 74 years [ mean age 60.8 + /- 6.3 ( SD ) ] who had had a myocardial infa rct ion and from 96 matched control subjects in the Honolulu Heart Program . Established risk factors for myocardial infa rct ion were measured prospect ively . No significant difference between patients and control subjects in mean estradiol or testosterone level was observed . The only established risk factor that was significantly different was blood pressure , which was higher in the patients . Thus , the data did not confirm the hypothesis . However , two major pitfalls for prospect i ve studies of estradiol in myocardial infa rct ion , which might have affected the validity of the results , were observed , namely , deterioration of estradiol values with prolonged storage ( 8.5 - 12 years in this study ) and intervention . The value of this study , therefore , may lie in pointing out difficulties in carrying out prospect i ve studies on sex hormones Circulating testosterone levels ( T ) decrease with age in men . Low T has been associated with coronary disease and with risk factors for atherosclerosis . This study examines the relationship in men between and rogenic hormones and arterial stiffness , a major risk factor for cardiovascular events . T , sex hormone-binding globulin ( SHBG ) , and dehydroepi and rosterone sulfate ( DHEAS ) were measured longitudinally over 33 yr ( follow-up 11.8 + /- 8.3 yr ) in 901 men from the Baltimore Longitudinal Study of Aging , of whom 206 ( 68.1 + /- 13.7 yr ) underwent carotid duplex ultrasonography .  The 901 men were used to characterize age-associated hormone levels by means of mixed-effects models . Hormone values were estimated for the 206 men at the time of ultrasonography . Free T index ( FTI ) was calculated by dividing T by SHBG . The arterial stiffness index was calculated from peak systolic and end diastolic diameters of the common carotid artery and simultaneous brachial artery blood pressure . T , FTI , and DHEAS were correlated negatively with age , pulse pressure ( PP ) , and stiffness index ( each P < 0.01 ) , whereas SHBG was correlated positively with age and stiffness index ( P < 0.01 ) . However , T was the only hormone that predicted the stiffness index after adjustment for age , PP , fasting plasma glucose , body mass index , and total cholesterol . T values 5 -  
    Output:
    
agent
Age of study population and year of publication modified the relationship between testosterone and CVD .
Results were largely confirmed by separate analyses of free- and bioavailable testosterone .
The systematic review displayed no association between endogenous testosterone and risk for CVD in middle-aged men .
In elderly men , testosterone may weakly protect against CVD .
Alternatively , low testosterone may indicate a poor general health
***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: CONTEXT Lower circulating testosterone concentrations are associated with metabolic syndrome , type 2 diabetes , carotid intima-media thickness , and aortic and lower limb arterial disease in men . However , it is unclear whether lower testosterone levels predict major cardiovascular events . OBJECTIVE We examined whether lower serum testosterone was an independently significant risk factor for symptomatic cerebrovascular events  in older men . DESIGN This was a prospect i ve observational study with median follow-up of 3.5 yr . SETTING Community-dwelling , stroke-free older men were studied . PARTICIPANTS A total of 3443 men at least 70 yr of age participated in the study . MAIN OUTCOME MEASURES  Baseline serum total testosterone , SHBG , and LH were assayed . Free testosterone  was calculated using mass action equations . Incident stroke or transient ischemic attack ( TIA ) was recorded . RESULTS A first stroke or TIA occurred in 119 men ( 3.5 % ) .  Total and free testosterone concentrations in the lowest quartiles ( < 11.7 nmol/liter and < 222 pmol/liter ) were associated with reduced event-free survival ( P = 0.014 and P = 0.01 , respectively ) . After adjustment including age , waist-hip ratio , waist circumference , smoking , hypertension , dyslipidemia , and medical comorbidity , lower total testosterone predicted increased incidence of stroke or TIA ( hazard ratio = 1.99 ; 95 % confidence interval , 1.33 - 2.99 ) . Lower free testosterone was also associated ( hazard ratio = 1.69 ; 95 % confidence interval , 1.15 - 2.48 ) , whereas SHBG and LH were not independently associated with incident stroke or TIA . CONCLUSIONS In older men , lower total testosterone levels predict increased incidence of stroke or TIA after adjusting for conventional risk factors for cardiovascular disease . Men with low-normal testosterone levels had increased risk . Further studies are warranted to determine whether interventions that raise circulating testosterone levels might prevent cerebrovascular disease in men CONTEXT Declining testosterone levels in elderly men are thought to underlie many of the symptoms and diseases of aging ; however , studies demonstrating associations of low testosterone with clinical outcomes are few . OBJECTIVE The objective of the study was to examine the association of endogenous testosterone levels with mortality in older community-dwelling men . DESIGN , SETTING , AND PARTICIPANTS This was a prospect i ve , population -based study of 794 men , aged 50 - 91 ( median 73.6 ) yr who had serum testosterone measurements at baseline ( 1984 - 1987 ) and were followed for mortality through July 2004 . MAIN OUTCOME MEASURE All-cause mortality by serum testosterone level  was measured . RESULTS During an average 11.8-yr follow-up , 538 deaths occurred . Men whose total testosterone levels were in the lowest quartile ( < 241 ng/dl ) were 40 % [ hazards ratio ( HR ) 1.40 ; 95 % confidence interval ( CI ) 1.14 - 1.71 ] more likely to die than those with higher levels , independent of age , adiposity , and lifestyle . Additional adjustment for health status markers , lipids , lipoproteins , blood pressure , glycemia , adipocytokines , and estradiol levels had minimal effect on results . The low testosterone-mortality association was also independent of the metabolic syndrome , diabetes , and prevalent cardiovascular disease but was attenuated by adjustment for IL-6 and C-reactive protein . In cause-specific analyses , low testosterone predicted increased risk of cardiovascular ( HR 1.38 ; 95 % CI 1.02 - 1.85 ) and respiratory disease ( HR 2.29 ; 95 % CI 1.25 - 4.20 ) mortality but was not significantly related to cancer death ( HR 1.34 ; 95 % CI 0.89 - 2.00 ) . Results were similar for bioavailable testosterone . CONCLUSIONS Testosterone insufficiency in older men is associated with increased risk of death over the following 20 yr , independent of multiple risk factors and several preexisting health conditions BACKGROUND Low serum testosterone is a common condition in aging associated with decreased muscle mass and insulin resistance . This study evaluated whether low testosterone levels are a risk factor for mortality in male veterans . METHODS We used a clinical data base to identify men older than 40 years with repeated testosterone levels obtained from October 1 , 1994 , to December 31 , 1999 , and without diagnosed prostate cancer . A low testosterone level was a total testosterone level of less than 250 ng/dL ( < 8.7 nmol/L ) or a free testosterone level of less than 0.75 ng/dL ( < 0.03 nmol/L ) . Men were classified as having a low testosterone level ( 166 [ 19.3 % ] ) , an equivocal testosterone level ( equal number of low and normal levels ) ( 240 [ 28.0 % ] ) , or a normal testosterone level ( 452 [ 52.7 % ] ) . The risk for all-cause mortality was estimated using Cox proportional hazards regression models , adjusting for demographic and clinical covariates over a follow-up of up to 8 years . RESULTS Mortality in men with normal testosterone levels was 20.1 % ( 95 % confidence interval [ CI ] , 16.2%-24.1 % ) vs 24.6 % ( 95 % CI , 19.2%-30.0 % ) in men with equivocal testosterone levels and 34.9 % ( 95 % CI , 28.5%-41.4 % ) in men with low testosterone levels . After adjusting for age , medical morbidity , and other clinical covariates , low testosterone levels continued to be associated with increased mortality ( hazard ratio , 1.88 ; 95 % CI , 1.34 - 2.63 ; P<.001 ) while equivocal testosterone levels were not significantly different from normal testosterone levels ( hazard ratio , 1.38 ; 95 % CI , 0.99%-1.92 % ; P=.06 ) . In a sensitivity analysis , men who died within the first year ( 50 [ 5.8 % ] ) were excluded to minimize the effect of acute illness , and low testosterone levels continued to be associated with elevated mortality . CONCLUSIONS Low testosterone levels were associated with increased mortality in male veterans . Further prospect i ve studies are needed to examine the association between low testosterone levels and mortality Background —There is a popular belief that chronic stress causes heart disease through psychoneuroendocrine mechanisms . We have examined whether an elevated circulating cortisol-to-testosterone ratio increases the risk of ischemic heart disease . Methods and Results —We undertook a prospect i ve cohort study of 2512 men aged 45 to 59 years between 1979 and 1983 from Caerphilly , South Wales , with a mean follow-up of 16.5 years . Subjects underwent a clinical examination , and morning fasting blood sample s were taken for analysis of cortisol levels , testosterone levels , and other cardiovascular risk factors . The ratio of cortisol to testosterone showed weak associations with potential confounding factors but strong positive associations with components of the insulin resistance syndrome ( P<0.001 ) . A positive linear trend was seen across quintiles of cortisol : testosterone ratio for incident ischemic heart disease ( age-adjusted OR per z score change in ratio 1.22 , 95 % CI 1.07 to 1.38 , P=0.003 ) . This was markedly attenuated after adjustment for components of the insulin resistance syndrome ( age-adjusted OR per z score change in ratio 1.10 , 95 % CI 0.96 to 1.25 , P=0.18 ) . There was no association between the cortisol : testosterone ratio and other causes of death ( age-adjusted hazard ratio 0.99 , 95 % CI 0.88 to 1.11 , P=0.81 ) . Conclusions —This is the first population -based prospect i ve study that has found a specific association between cortisol : testosterone ratio and incident ischemic heart disease , apparently mediated through the insulin resistance syndrome . Whether this reflects the effects of chronic stress , behavioral factors , or genetic influences remains to be determined CONTEXT Age-related reduction of serum testosterone may contribute to the signs and symptoms of aging , but previous studies report conflicting evidence about testosterone levels and male mortality . No large prospect i ve cohort study has determined a possible association between serum estradiol and mortality in men . OBJECTIVE The main objective was to examine the association between serum testosterone and estradiol and all-cause mortality  in elderly men . DESIGN , SETTING , AND PARTICIPANTS We used specific gas chromatography-mass spectrometry to analyze serum sex steroids at baseline in older men who participated in the prospect i ve population -based MrOS Sweden cohort ( n = 3014 ; mean age , 75 yr ; range , 69 - 80 yr ) . MAIN OUTCOME MEASURE All-cause mortality by serum testosterone and estradiol levels . RESULTS During a mean follow-up period of 4.5 yr , 383 deaths occurred . In multivariate hazards regression models , low levels ( within quartile 1 vs. quartiles 2 - 4 ) of both testosterone [ hazard ratio ( HR ) , 1.65 ; 95 % confidence interval ( CI ) , 1.29 - 2.12 ] and estradiol ( HR , 1.54 ; 95 % CI , 1.22 - 1.95 ) associated with mortality . A model including both hormones showed that both low testosterone ( HR , 1.46 ; 95 % CI , 1.11 - 1.92 ) and estradiol ( HR , 1.33 ; 95 % CI , 1.02 - 1.73 ) predicted mortality . Risk of death nearly doubled ( HR , 1.96 ; 95 % CI , 1.46 - 2.62 ) in subjects with low levels of both testosterone and estradiol compared with subjects within quartiles 2 - 4 of both hormones . CONCLUSIONS Elderly men with low serum testosterone and estradiol have increased risk of mortality , and subjects with low values of both testosterone and estradiol have the highest risk of mortality It has been hypothesized that hyperestrogenemia may underlie myocardial infa rct ion . As a test of this hypothesis , the serum estradiol and testosterone levels were estimated in sample s collected prospect ively from 96 male patients aged 52 - 74 years [ mean age 60.8 + /- 6.3 ( SD ) ] who had had a myocardial infa rct ion and from 96 matched control subjects in the Honolulu Heart Program . Established risk factors for myocardial infa rct ion were measured prospect ively . No significant difference between patients and control subjects in mean estradiol or testosterone level was observed . The only established risk factor that was significantly different was blood pressure , which was higher in the patients . Thus , the data did not confirm the hypothesis . However , two major pitfalls for prospect i ve studies of estradiol in myocardial infa rct ion , which might have affected the validity of the results , were observed , namely , deterioration of estradiol values with prolonged storage ( 8.5 - 12 years in this study ) and intervention . The value of this study , therefore , may lie in pointing out difficulties in carrying out prospect i ve studies on sex hormones Circulating testosterone levels ( T ) decrease with age in men . Low T has been associated with coronary disease and with risk factors for atherosclerosis . This study examines the relationship in men between and rogenic hormones and arterial stiffness , a major risk factor for cardiovascular events . T , sex hormone-binding globulin ( SHBG ) , and dehydroepi and rosterone sulfate ( DHEAS ) were measured longitudinally over 33 yr ( follow-up 11.8 + /- 8.3 yr ) in 901 men from the Baltimore Longitudinal Study of Aging , of whom 206 ( 68.1 + /- 13.7 yr ) underwent carotid duplex ultrasonography .  The 901 men were used to characterize age-associated hormone levels by means of mixed-effects models . Hormone values were estimated for the 206 men at the time of ultrasonography . Free T index ( FTI ) was calculated by dividing T by SHBG . The arterial stiffness index was calculated from peak systolic and end diastolic diameters of the common carotid artery and simultaneous brachial artery blood pressure . T , FTI , and DHEAS were correlated negatively with age , pulse pressure ( PP ) , and stiffness index ( each P < 0.01 ) , whereas SHBG was correlated positively with age and stiffness index ( P < 0.01 ) . However , T was the only hormone that predicted the stiffness index after adjustment for age , PP , fasting plasma glucose , body mass index , and total cholesterol . T values 5 -  
    Output:
    