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: In order to determine whether treatment of hyperlipidaemia with simvastatin impairs exercise stress responses and so may contribute to an excess of suicides and violent deaths , the effects of simvastatin 20 mg daily and placebo on exercise physiology were compared in 19 patients . After 6 weeks of treatment there was no evidence of reduced exercise capacity , or of reduced cortisol or catecholamine responses . It is concluded that treatment of hyperlipidaemia with an inhibitor of HMG-CoA reductase does not significantly modify stress responses , and so the explanation for a possible increase in non-cardiac mortality must be sought elsewhere Objective . The present study was design ed to evaluate the lipid-altering efficacy , safety , and tolerability of lovastatin treatment in adolescent girls with heterozygous familial hypercholesterolemia . Methods . A total of 54 postmenarchal girls , aged 10 to 17 years , were enrolled in a 24-week , double-blind , r and omized , placebo-controlled study . After a 4-week diet/placebo run-in period , patients were r and omized to 1 of 2 groups : ( 1 ) treatment with diet plus lovastatin 20 mg/day for 4 weeks , followed by diet plus lovastatin 40 mg/day for 20 weeks , or ( 2 ) diet plus placebo for 24 weeks . Results . Baseline values of lipids , lipoproteins , and apolipoproteins ( apo ) were comparable between treatment groups . Lovastatin treatment was efficacious at reducing low-density lipoprotein cholesterol by 23 % to 27 % , total cholesterol by 17 % to 22 % , and apo B by 20 % to 23 % at weeks 4 and 24 , respectively . Between-treatment group differences were not statistically significant for triglycerides , very-low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , or apo A-I.  Lovastatin was generally safe and well tolerated . There were no clinical ly significant alterations in vital signs ( blood pressure and pulse rate ) , anthropomorphic measurements ( height , weight , and BMI ) , hormone levels ( luteinizing hormone , follicle-stimulating hormone , dehydroepi and rosterone sulfate , estradiol , and cortisol ) , menstrual cycle length , or tests of liver and muscle function . Conclusions . Lovastatin offers an efficacious and well-tolerated treatment option for improving lipid profiles in adolescent girls with familial hypercholesterolemia CONTEXT Heterozygous familial hypercholesterolemia ( HeFH ) is a common disorder associated with early coronary artery disease , especially in men . The age at which drug therapy should be started is still controversial , as is the use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) . OBJECTIVE To assess the lipid-lowering efficacy , biochemical safety , and effect on growth and sexual development of lovastatin in adolescent boys with HeFH . DESIGN One-year , double-blind , placebo-controlled , balanced , 2-period , 2-arm r and omized trial . In the first period ( 24 weeks ) , lovastatin was increased at 8 and 16 weeks and the dosage remained stable during the second period ( 24 weeks ) . The study was conducted between 1990 and 1994 . SETTING Fourteen pediatric outpatient clinics in the United States and Finl and . PATIENTS Boys aged 10 to 17 years with HeFH . Of 132 r and omized subjects ( 67 intervention , 65 placebo ) , 122 ( 63 intervention , 59 placebo ) and 110 ( 61 intervention , 49 placebo ) completed the first and second periods , respectively . INTERVENTION Lovastatin , starting at 10 mg/d , with a forced titration at 8 and 16 weeks to 20 and 40 mg/d , respectively , or placebo . MAIN OUTCOME MEASURES The primary efficacy outcome measure was low-density lipoprotein cholesterol ( LDL-C ) . Primary safety measures were growth and sexual development . RESULTS Compared with placebo , LDL-C levels of patients receiving lovastatin decreased significantly ( P<.001 ) by 17 % , 24 % , and 27 % receiving dosages of 10 , 20 , and 40 mg/d , respectively , and remained 25 % lower than baseline at 48 weeks . Growth and sexual maturation assessed by Tanner staging and testicular volume were not significantly different between the lovastatin and placebo groups at 24 weeks ( P = .85 ) and 48 weeks ( P = .33 ) ; neither were serum hormone levels or biochemical parameters of nutrition . However , the study was underpowered to detect significant differences in safety parameters . Serum vitamin E levels were reduced with lovastatin treatment consistent with reductions in LDL-C , the major carrier of vitamin E in the circulation . CONCLUSIONS This study in adolescent boys with HeFH confirmed the LDL-C-reducing effectiveness of lovastatin . Comprehensive clinical and biochemical data on growth , hormonal , and nutritional status indicated no significant differences between lovastatin and placebo over 48 weeks , although further study is required Effects of cortisol on human mood during stress situations are still incompletely understood , although this topic has important clinical implication s. In this experiment , the mood of 44 healthy young women ( all oral contraceptive users ) was examined . A double-blind , r and omized , placebo-controlled time series paradigm was used . Subjects were treated with either 30-mg cortisol or placebo orally . Forty-five minutes later , subjects attended a psychosocial stress procedure ( Trier Social Stress Test ; TSST ; C. Kirschbaum , K. M. Pirke , & D. H. Hellhammer , 1993 ) . The course of the subjects ' mood as well as salivary cortisol and alpha-amylase levels were measured before and after the TSST . With regard to mood , it was found that the groups did not differ in mood before the TSST . After stress exposure , the subjective ratings of current mood state of cortisol-treated women were significantly less negative than that of placebo-treated subjects . These findings show that raising cortisol levels prior to acute stress has a protective effect on mood during stress situations . Results are discussed with regard to the context of specific adaptive effects of cortisol and the role of cortisol in posttraumatic stress disorder Statine reduzieren die Cholesterin- und Isoprenoid-de-novo-Biosynthese , darüber hinaus die rezeptorvermittelte Aufnahme von Cholesterin für die Steroidhormonsynthese . In der vorgelegten r and omisierten , placebo-kontrollierten Studie wurde der Effekt von Pravastatin ( 40 mg/Tag ) auf die Plasmakonzentrationen von Steroidhormonen und Gonadotropinen untersucht . Die Patienten ( n = 22 ; 15 Männer , 7 Frauen ) wurden mit Pravastatin 40 mg/Tag oder Placebo beh and elt . Die Konzentrationen des Gesamtcholesterins sowie des LDL-Cholesterins und der Steroidhormone Östradiol , Testosteron , Cortisol und Dehydroepi and rosteron-Sulfat ( DHEAS ) sowie der Gonadotropine FSH und LH wurden untersucht . Pravastatin führte zu einer signifikanten Reduktion der Serumkonzentration des Gesamtcholesterins und des LDL-Cholesterins . Signifikante Veränderungen von Östradiol , Testosteron , Cortisol oder DHEAS wurden nicht beobachtet . Kompensatorische Veränderungen von FSH oder LH f and en sich nicht . Es wird schlussgefolgert , dass die Pravastatin-Therapie , die zu einer signifikanten Reduktion des Gesamtcholesterins und des LDL-Cholesterins führte , in therapeutisch verwendeten Dosierungen keinen Einfluss auf die Steroidhormon- Synthese oder die Freisetzung von Gonadotropinen hat . Statins reduce cholesterol and isoprenoid de novo bio synthesis as well as receptormediated uptake of cholesterol for steroidogenesis . The present r and omized placebo-controlled trial investigated whether pravastatin ( 40 mg/day ) reduces the plasma concentrations of steroid hormones as well as of gonadotropins .  Patients ( n = 22 ; 15 males , 7 females ) were treated with pravastatin ( 40 mg/day ) or placebo . Levels of total and LDL cholesterol , the steroid hormones estradiol , testosterone , cortisol and dehydroepi and rosterone sulphate ( DHEAS ) as well as FSH and LH were studied . Pravastatin led to a significant reduction of total cholesterol and LDL cholesterol . There was no significant change in estradiol , testosterone , cortisol or DHEAS plasma concentrations . There was no compensatory change in FSH or LH . It is concluded that pravastatin does not alter steroid hormones or gonadotropins in a clinical ly applicable dose , which significantly reduces total and LDL cholesterol In this open-label , balanced , r and omized , placebo-controlled , parallel study , healthy male volunteers were r and omly divided into two groups . Each group received either a single oral dose of rosuvastatin 20 mg or placebo . Estimations were done at predose on day 1 of dosing ( baseline ) and 24 h postdose after days 7 and 14 . Serum cortisol and serum lipid levels were estimated using enzyme-linked immunosorbent assay kits and serum mevalonic acid ( MVA ) levels were measured using vali date d liquid chromatography – t and em mass spectrometry method . Rosuvastatin produced a statistically significant ( P < 0.05 ) decrease in total cholesterol , low-density lipoprotein cholesterol , very low-density lipoprotein cholesterol , and triglycerides . However , the increase in high-density lipoprotein cholesterol and decrease in cortisol and MVA were not statistically significant when compared to the placebo-treated group . The study showed that rosuvastatin at a dose of 20 mg/day for a period of 14 days was very potent as cholesterol-lowering agent , without any significant change in serum cortisol level in the healthy Indian male population BACKGROUND The West of Scotl and Coronary Prevention Study was a r and omized clinical trial comparing pravastatin with placebo in men with hypercholesterolemia who did not have a history of myocardial infa rct ion , with an average follow-up of approximately 5 years . The combined outcome of death from definite coronary heart disease or definite nonfatal myocardial infa rct ion was reduced from 7.9 to 5.5 % ( P<0.001 ) in the treatment group . Extended follow-up data were obtained for approximately 10 years after completion of the trial . METHODS For the survivors of the trial , all deaths , hospitalizations and deaths due to coronary events and stroke , and incident cancers and deaths from cancer were tracked with the use of a national computerized record-linkage system . The results were analyzed with time-to-event analyses and use of Cox proportional-hazards models . RESULTS Five years after the trial ended , 38.7 % of the original statin group and 35.2 % of the original placebo group were being treated with a statin . In the period approximately 10 years after completion of the trial , the risk of death from coronary heart disease or nonfatal myocardial infa rct ion was 10.3 % in the placebo group and 8.6 % in the pravastatin group ( P=0.02 ) ; over the entire follow-up period , the rate was 15.5 % in the placebo group and 11.8 % in the pravastatin group ( P<0.001 ) . Similar percentage reductions were seen in the combined rate of death from coronary heart disease and hospitalization for coronary events for both periods . The rate of death from cardiovascular causes was reduced ( P=0.01 ) , as was the rate of death from any cause ( P=0.03 ) , over the entire follow-up period . There were no excess deaths from noncardiovascular causes or excess fatal or incident cancers . CONCLUSIONS In this analysis , 5 years of treatment with pravastatin was associated with a significant reduction in coronary events for a subsequent 10 years in men with hypercholesterolemia who did not have a history of myocardial infa rct ion Objective —The intercellular adhesion molecule-1 ( ICAM-1/CD54 ) and its lig and , CD11a/CD18 , mediate endothelial adhesion of leukocytes and their consecutive transmigration . Anti-inflammatory effects of statins are considered to be exerted in part through inhibition of leukocyte – endothelial interactions . We investigated the in vivo effects of simvastatin treatment in hypercholesterolemic patients and the influence of various statins on expression of cellular adhesion molecules in vitro . Methods and Results —A total number of 107 hypercholesterolemic patients were treated with 20 mg ( n=52 ) or 40 mg ( n=55 ) of simvastatin daily . After 6 weeks of treatment , peripheral blood mononuclear cells ( P BMC s ) expressed lower amounts of CD54- , CD18- , and CD11a-mRNA compared with pretreatment values . Surface expression 
    Output:
    
agent
In the meta-regression analysis , changes in plasma cortisol concentrations following statin therapy were found to be independent of treatment duration .
Results of this meta- analysis of RCTs suggest a significant elevation in plasma cortisol levels following statin therapy
***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: In order to determine whether treatment of hyperlipidaemia with simvastatin impairs exercise stress responses and so may contribute to an excess of suicides and violent deaths , the effects of simvastatin 20 mg daily and placebo on exercise physiology were compared in 19 patients . After 6 weeks of treatment there was no evidence of reduced exercise capacity , or of reduced cortisol or catecholamine responses . It is concluded that treatment of hyperlipidaemia with an inhibitor of HMG-CoA reductase does not significantly modify stress responses , and so the explanation for a possible increase in non-cardiac mortality must be sought elsewhere Objective . The present study was design ed to evaluate the lipid-altering efficacy , safety , and tolerability of lovastatin treatment in adolescent girls with heterozygous familial hypercholesterolemia . Methods . A total of 54 postmenarchal girls , aged 10 to 17 years , were enrolled in a 24-week , double-blind , r and omized , placebo-controlled study . After a 4-week diet/placebo run-in period , patients were r and omized to 1 of 2 groups : ( 1 ) treatment with diet plus lovastatin 20 mg/day for 4 weeks , followed by diet plus lovastatin 40 mg/day for 20 weeks , or ( 2 ) diet plus placebo for 24 weeks . Results . Baseline values of lipids , lipoproteins , and apolipoproteins ( apo ) were comparable between treatment groups . Lovastatin treatment was efficacious at reducing low-density lipoprotein cholesterol by 23 % to 27 % , total cholesterol by 17 % to 22 % , and apo B by 20 % to 23 % at weeks 4 and 24 , respectively . Between-treatment group differences were not statistically significant for triglycerides , very-low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , or apo A-I.  Lovastatin was generally safe and well tolerated . There were no clinical ly significant alterations in vital signs ( blood pressure and pulse rate ) , anthropomorphic measurements ( height , weight , and BMI ) , hormone levels ( luteinizing hormone , follicle-stimulating hormone , dehydroepi and rosterone sulfate , estradiol , and cortisol ) , menstrual cycle length , or tests of liver and muscle function . Conclusions . Lovastatin offers an efficacious and well-tolerated treatment option for improving lipid profiles in adolescent girls with familial hypercholesterolemia CONTEXT Heterozygous familial hypercholesterolemia ( HeFH ) is a common disorder associated with early coronary artery disease , especially in men . The age at which drug therapy should be started is still controversial , as is the use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) . OBJECTIVE To assess the lipid-lowering efficacy , biochemical safety , and effect on growth and sexual development of lovastatin in adolescent boys with HeFH . DESIGN One-year , double-blind , placebo-controlled , balanced , 2-period , 2-arm r and omized trial . In the first period ( 24 weeks ) , lovastatin was increased at 8 and 16 weeks and the dosage remained stable during the second period ( 24 weeks ) . The study was conducted between 1990 and 1994 . SETTING Fourteen pediatric outpatient clinics in the United States and Finl and . PATIENTS Boys aged 10 to 17 years with HeFH . Of 132 r and omized subjects ( 67 intervention , 65 placebo ) , 122 ( 63 intervention , 59 placebo ) and 110 ( 61 intervention , 49 placebo ) completed the first and second periods , respectively . INTERVENTION Lovastatin , starting at 10 mg/d , with a forced titration at 8 and 16 weeks to 20 and 40 mg/d , respectively , or placebo . MAIN OUTCOME MEASURES The primary efficacy outcome measure was low-density lipoprotein cholesterol ( LDL-C ) . Primary safety measures were growth and sexual development . RESULTS Compared with placebo , LDL-C levels of patients receiving lovastatin decreased significantly ( P<.001 ) by 17 % , 24 % , and 27 % receiving dosages of 10 , 20 , and 40 mg/d , respectively , and remained 25 % lower than baseline at 48 weeks . Growth and sexual maturation assessed by Tanner staging and testicular volume were not significantly different between the lovastatin and placebo groups at 24 weeks ( P = .85 ) and 48 weeks ( P = .33 ) ; neither were serum hormone levels or biochemical parameters of nutrition . However , the study was underpowered to detect significant differences in safety parameters . Serum vitamin E levels were reduced with lovastatin treatment consistent with reductions in LDL-C , the major carrier of vitamin E in the circulation . CONCLUSIONS This study in adolescent boys with HeFH confirmed the LDL-C-reducing effectiveness of lovastatin . Comprehensive clinical and biochemical data on growth , hormonal , and nutritional status indicated no significant differences between lovastatin and placebo over 48 weeks , although further study is required Effects of cortisol on human mood during stress situations are still incompletely understood , although this topic has important clinical implication s. In this experiment , the mood of 44 healthy young women ( all oral contraceptive users ) was examined . A double-blind , r and omized , placebo-controlled time series paradigm was used . Subjects were treated with either 30-mg cortisol or placebo orally . Forty-five minutes later , subjects attended a psychosocial stress procedure ( Trier Social Stress Test ; TSST ; C. Kirschbaum , K. M. Pirke , & D. H. Hellhammer , 1993 ) . The course of the subjects ' mood as well as salivary cortisol and alpha-amylase levels were measured before and after the TSST . With regard to mood , it was found that the groups did not differ in mood before the TSST . After stress exposure , the subjective ratings of current mood state of cortisol-treated women were significantly less negative than that of placebo-treated subjects . These findings show that raising cortisol levels prior to acute stress has a protective effect on mood during stress situations . Results are discussed with regard to the context of specific adaptive effects of cortisol and the role of cortisol in posttraumatic stress disorder Statine reduzieren die Cholesterin- und Isoprenoid-de-novo-Biosynthese , darüber hinaus die rezeptorvermittelte Aufnahme von Cholesterin für die Steroidhormonsynthese . In der vorgelegten r and omisierten , placebo-kontrollierten Studie wurde der Effekt von Pravastatin ( 40 mg/Tag ) auf die Plasmakonzentrationen von Steroidhormonen und Gonadotropinen untersucht . Die Patienten ( n = 22 ; 15 Männer , 7 Frauen ) wurden mit Pravastatin 40 mg/Tag oder Placebo beh and elt . Die Konzentrationen des Gesamtcholesterins sowie des LDL-Cholesterins und der Steroidhormone Östradiol , Testosteron , Cortisol und Dehydroepi and rosteron-Sulfat ( DHEAS ) sowie der Gonadotropine FSH und LH wurden untersucht . Pravastatin führte zu einer signifikanten Reduktion der Serumkonzentration des Gesamtcholesterins und des LDL-Cholesterins . Signifikante Veränderungen von Östradiol , Testosteron , Cortisol oder DHEAS wurden nicht beobachtet . Kompensatorische Veränderungen von FSH oder LH f and en sich nicht . Es wird schlussgefolgert , dass die Pravastatin-Therapie , die zu einer signifikanten Reduktion des Gesamtcholesterins und des LDL-Cholesterins führte , in therapeutisch verwendeten Dosierungen keinen Einfluss auf die Steroidhormon- Synthese oder die Freisetzung von Gonadotropinen hat . Statins reduce cholesterol and isoprenoid de novo bio synthesis as well as receptormediated uptake of cholesterol for steroidogenesis . The present r and omized placebo-controlled trial investigated whether pravastatin ( 40 mg/day ) reduces the plasma concentrations of steroid hormones as well as of gonadotropins .  Patients ( n = 22 ; 15 males , 7 females ) were treated with pravastatin ( 40 mg/day ) or placebo . Levels of total and LDL cholesterol , the steroid hormones estradiol , testosterone , cortisol and dehydroepi and rosterone sulphate ( DHEAS ) as well as FSH and LH were studied . Pravastatin led to a significant reduction of total cholesterol and LDL cholesterol . There was no significant change in estradiol , testosterone , cortisol or DHEAS plasma concentrations . There was no compensatory change in FSH or LH . It is concluded that pravastatin does not alter steroid hormones or gonadotropins in a clinical ly applicable dose , which significantly reduces total and LDL cholesterol In this open-label , balanced , r and omized , placebo-controlled , parallel study , healthy male volunteers were r and omly divided into two groups . Each group received either a single oral dose of rosuvastatin 20 mg or placebo . Estimations were done at predose on day 1 of dosing ( baseline ) and 24 h postdose after days 7 and 14 . Serum cortisol and serum lipid levels were estimated using enzyme-linked immunosorbent assay kits and serum mevalonic acid ( MVA ) levels were measured using vali date d liquid chromatography – t and em mass spectrometry method . Rosuvastatin produced a statistically significant ( P < 0.05 ) decrease in total cholesterol , low-density lipoprotein cholesterol , very low-density lipoprotein cholesterol , and triglycerides . However , the increase in high-density lipoprotein cholesterol and decrease in cortisol and MVA were not statistically significant when compared to the placebo-treated group . The study showed that rosuvastatin at a dose of 20 mg/day for a period of 14 days was very potent as cholesterol-lowering agent , without any significant change in serum cortisol level in the healthy Indian male population BACKGROUND The West of Scotl and Coronary Prevention Study was a r and omized clinical trial comparing pravastatin with placebo in men with hypercholesterolemia who did not have a history of myocardial infa rct ion , with an average follow-up of approximately 5 years . The combined outcome of death from definite coronary heart disease or definite nonfatal myocardial infa rct ion was reduced from 7.9 to 5.5 % ( P<0.001 ) in the treatment group . Extended follow-up data were obtained for approximately 10 years after completion of the trial . METHODS For the survivors of the trial , all deaths , hospitalizations and deaths due to coronary events and stroke , and incident cancers and deaths from cancer were tracked with the use of a national computerized record-linkage system . The results were analyzed with time-to-event analyses and use of Cox proportional-hazards models . RESULTS Five years after the trial ended , 38.7 % of the original statin group and 35.2 % of the original placebo group were being treated with a statin . In the period approximately 10 years after completion of the trial , the risk of death from coronary heart disease or nonfatal myocardial infa rct ion was 10.3 % in the placebo group and 8.6 % in the pravastatin group ( P=0.02 ) ; over the entire follow-up period , the rate was 15.5 % in the placebo group and 11.8 % in the pravastatin group ( P<0.001 ) . Similar percentage reductions were seen in the combined rate of death from coronary heart disease and hospitalization for coronary events for both periods . The rate of death from cardiovascular causes was reduced ( P=0.01 ) , as was the rate of death from any cause ( P=0.03 ) , over the entire follow-up period . There were no excess deaths from noncardiovascular causes or excess fatal or incident cancers . CONCLUSIONS In this analysis , 5 years of treatment with pravastatin was associated with a significant reduction in coronary events for a subsequent 10 years in men with hypercholesterolemia who did not have a history of myocardial infa rct ion Objective —The intercellular adhesion molecule-1 ( ICAM-1/CD54 ) and its lig and , CD11a/CD18 , mediate endothelial adhesion of leukocytes and their consecutive transmigration . Anti-inflammatory effects of statins are considered to be exerted in part through inhibition of leukocyte – endothelial interactions . We investigated the in vivo effects of simvastatin treatment in hypercholesterolemic patients and the influence of various statins on expression of cellular adhesion molecules in vitro . Methods and Results —A total number of 107 hypercholesterolemic patients were treated with 20 mg ( n=52 ) or 40 mg ( n=55 ) of simvastatin daily . After 6 weeks of treatment , peripheral blood mononuclear cells ( P BMC s ) expressed lower amounts of CD54- , CD18- , and CD11a-mRNA compared with pretreatment values . Surface expression 
    Output:
    