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: Seventy girls with Turner syndrome , verified by karyotype , were r and omly assigned to observation or treatment with human growth hormone ( hGH ) , ox and rolone , or a combination of hGH plus ox and rolone for a period of 12 to 24 months , to assess the effect of treatment on growth velocity and adult height . Subsequently , all subjects received either hGH alone or hGH plus ox and rolone . Data are presented for 62 subjects treated for a period of 3 to 6 years . When compared with the anticipated growth rate in untreated patients , the growth rate after treatment with hGH , both alone and in combination with ox and rolone , showed a sustained increase for at least 6 years . Treatment is continuing in over half of the subjects ; at present , 14 ( 82 % ) of 17 girls receiving hGH alone and 41 ( 91 % ) of 45 girls receiving combination therapy exceeded their expected adult heights .  Thirty girls have completed treatment ; mean height for these 30 patients is 151.9 cm , compared with their mean original projected adult height of 143.8 cm . We conclude that therapy with hGH , alone and in combination with ox and rolone , can result in a sustained increase in growth rate and a significant increase in adult height for most prepubertal girls with Turner syndrome In 1983 , a multicenter , collaborative , prospect i ve study was begun to investigate the efficacy of human growth hormone ( hGH ) , alone and in combination with ox and rolone , in girls with Turner syndrome . While subjects in the control group grew 3.8 cm/yr ( -0.1 SD for untreated Turner patients ) , subjects receiving hGH alone  grew 6.6 , 5.4 and 4.6 cm/yr in years 1 - 3 , respectively ( + 3.1 , + 2.0 , + 1.4 SD ) . Subjects in the combination therapy group grew 9.8 , 7.4 and 6.1 cm/yr ( + 6.6 , + 4.3 , + 3.0 SD ) . Turner subjects in both treatment groups showed increased in Bayley-Pinneau predicted adult heights and in Turner projected adult heights Preliminary results are presented after 2 years of the Canadian long-term multicentre study on the impact of hormone therapy on the final height , sexual development and psychological status of girls with Turner syndrome . Girls entering the study were r and omized either to be treated with recombinant human growth hormone or to act as controls . Both groups received oestrogen replacement therapy in the same dose and format at the age of 13 years . However , for the purpose s of the psychological study at this time , children receiving oestrogen were excluded from analysis . Girls treated with GH for a period of 2 years showed a significant increase in growth rate , which declined with continued treatment , while the growth rate in the control group remained constant throughout . There was a correlation between the higher growth rate and the girls ' perceptions of themselves as more intelligent , more attractive , having more friends , greater popularity and experiencing less teasing than the untreated group . Growth rate was not correlated with family or school functioning STUDY OBJECTIVE To determine the influence of the injection frequency and the initial bone age on the efficacy of treatment with biosynthetic growth hormone in Turner 's syndrome . DESIGN R and omized study . SETTING Referral-based pediatric endocrinology departments of seven university medical centers . PATIENTS Fifty-two patients with Turner 's syndrome confirmed with chromosomal analysis . TREATMENT Somatotropin recombinant DNA ( 24 IU/m2 of body surface area ) subcutaneously administered in three or six injections per week for 2 years . Patients who were older than 12 years at the beginning of the study received low doses of estrogen . RESULTS The following statistically significant findings supported the use of six injections per week compared with three injections per week : the mean ( + /- SD ) increment in height during 2 years was 11.3 cm ( 3.8 cm ) with six injections vs 8.6 cm ( 3.4 cm ) with three injections ; the increment in height st and ard deviation score was 0.9 cm ( 0.5 cm ) vs 0.6 cm ( 0.3 cm ) ; the growth velocity was 6.6 cm/y ( 2.0 cm/y ) vs 5.2 cm/y ( 1.7 cm/y ) in year 1 and 4.7 cm/y ( 2.0 cm/y ) vs 3.4 cm/y ( 1.7 cm/y ) in year 2 ; and the increment in height st and ard deviation score for bone age was 0.8 cm ( 0.5 cm ) vs 0.4 cm ( 0.6 cm ) . For patients whose initial bone age was more than 13 years , growth velocity increased by 1 to 2 cm in year 1 ; in year 2 no increment was observed . We did not observe adverse effects . CONCLUSIONS Biosynthetic growth hormone in a higher-frequency regimen in Turner 's syndrome is more efficient in terms of increment in height , growth velocity , and height st and ard deviation score for bone age than treatment in a lower-frequency regimen . In patients with an initial bone age of more than 13 years , the response was poor . Longer follow-up is necessary to assess the effect on final height OBJECTIVES To study final height in girls with Turner ’s syndrome treated with once or twice daily injections of growth hormone ( GH ) in combination with low dose ethinyl oestradiol . DESIGN Until final height was reached , the effect of fractionated subcutaneous injections given twice daily was compared with once daily injections of a total GH dose of 6 IU/m2/day . Twice daily injections were given as one third in the morning and two thirds at bedtime . All girls concurrently received low dose oestradiol ( 0.05 μg ethinyl oestradiol/kg/day , increased to 0.10 μg/kg/day after 2.25 years ) . PATIENTS Nineteen girls with Turner ’s syndrome aged ⩾ 11 years ( mean ( SD ) 13.6 ( 1.7 ) years ) . MEASUREMENTS To determine final height gain , we assessed the difference between the attained final height and the final height predictions at the start of treatment . These final height predictions were calculated using the Bayley-Pinneau ( BP ) prediction method , the modified projected adult height ( mPAH ) , the modified index of potential height ( mIPHRUS ) , and the Turner ’s specific prediction method ( PTSRUS ) . RESULTS The gain in final height ( mean ( SD ) ) was not significantly different between the once daily and the twice daily regimens ( 7.6 ( 2.3 ) v 5.1 ( 3.2 ) cm ) . All girls exceeded their adult height prediction ( range , 1.6–12.3 cm ) . Thirteen of the 19 girls  had a final height gain > 5.0 cm . Mean ( SD ) attained final height was 155.5 ( 5.4 ) cm . A “ younger bone age ” at baseline and a higher increase in height st and ard deviation score for chronological age ( Dutch – Swedish – Danish references ) in the first year of GH treatment predicted a higher final height gain  after GH treatment . CONCLUSIONS Division of the total daily GH dose ( 6 IU/m2/day ) into two thirds in the evening and one third in the morning is not advantageous over the once daily GH regimen with respect to final height gain . Treatment with a GH dose of 6 IU/m2/day in combination with low dose oestrogens can result in a significant increase in adult height in girls with Turner ’s syndrome , even if they start GH treatment at a relatively late age Forty patients with Turner 's syndrome , aged 5.0 - 16.6 yr , were r and omly allocated to receive daily sc injections of recombinant human GH ( hGH ) at a dose of 1 IU/kg.week alone ( group I ) or in combination with 25 ng/kg.day ethinyl estradiol ( E2 ; group II ) . The mean pretreatment height velocity was 3.8 cm/yr for both groups . During the first year of treatment height velocity increased significantly ( P less than 0.001 ) in both groups , to 7.5 + /- 1.3 and 8.1 + /- 1.6 cm/yr , respectively . The difference between the two groups was not significant . The mean ( + /- SD ) height velocity expressed as the SD score for chronological age ( Turner references ) was 0.0 + /- 1.2 for group I and 0.2 + /- 1.4 for group II and increased significantly ( P less than 0.001 ) during the first year of treatment to + 4.3 + /- 1.1 in group I and + 5.4 + /- 1.2 in group II . The difference between both groups was statistically significant ( P less than 0.01 ) . Height SD score for chronological age ( Turner references ) increased from -0.2 + /- 0.9 to + 0.6 + /- 1.0 in group I and from -0.2 + /- 1.0 to + 0.7 + /- 1.1 in group II . Mean bone age progressed similarly in both treatment groups ( 1.1 + /- 0.6 yr during 1 yr of treatment ) . However , bone age maturation accelerated more rapidly in younger patients . Twelve girls ( three in group I and nine in group II ) had minor breast development . No major adverse effects were reported . We conclude that daily sc therapy with hGH stimulates height velocity in Turner 's syndrome . The beneficial effect on height velocity increment of E2 addition was small . Furthermore , even very low doses of E2 may induce breast development at an early age and accelerate bone maturation . For these reasons , the addition of E2 to hGH is not warranted in young patients with Turner 's syndrome 91 girls with Turner syndrome ( TS ) with a mean chronological age ( CA ) and bone age ( BA ) of 10.3 + /- 2.3 and 8.9 + /- 1.9 years , respectively , were r and omly assigned to subcutaneous treatment with recombinant human growth hormone ( rhGH ) alone ( n = 47 ) , 2.6 IU/m2 body surface area daily or combination treatment ( n = 44 ) with the same dose of rhGH and ox and rolone 0.1 mg/kg body weight orally , for the first 12 months of this study . During the 1st year of therapy , there was a striking increase in height velocity ( HV ) in both groups , from 4.0 + /- 0.8 to 6.3 + /- 1.3 cm/year [ HV st and ard ( st and ards of untreated Turner patients ) deviation score ( SDS ) for CA from 0.0 + /- 0.7 to 2.9 + /- 1.3 ] in the rhGH group and from 4.2 + /- 1.2 to 8.5 + 2- 1.7 cm/year ( HV SDS-CA from + 0.3 + /- 1.0 to 5.6 + /- 1.6 ) in the combination group . The difference between the groups was statistically significant ( p < 0.01 ) . During the 2nd year of treatment , the rhGH dose was increased to 3.4 IU/m2 daily for the rhGH-alone group , whereas in the combination treatment group the ox and rolone dose was reduced to 0.05 mg/kg daily . HV was maintained at significantly higher levels than those prior to treatment , at 5.3 + /- 1.1 cm/year ( HV SDS-CA : + 2.1 + /- 1.3 ) and 6.2 + /- 1.5 cm/year ( HV SDS-CA : + 3.6 + /- 1.4 ) in the rhGH-alone and the combination group , respectively ( p < 0.001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To carry out a multicenter , prospect i ve , r and omized trial of human growth hormone ( GH ) , alone or in combination with ox and rolone ( OX ) , in patients with Turner 's syndrome ( TS ) . METHODS In an initial phase lasting 12 to 24 months , 70 girls with TS , verified by karyotype , were r and omly assigned to one of four groups : ( 1 ) observation , ( 2 ) OX , ( 3 ) GH , or ( 4 ) GH plus OX . After completion of the first phase , group 3 subjects continued to receive GH only . All other subjects were treated with GH plus OX . Subjects were followed up until attainment of adult height and /or cessation of treatment . Data from this trial were compared with growth characteristics of 25 American historical subjects with TS ( matched for age , height , parental target height , and karyotype ) who never received either GH or and rogens .  RESULTS Of the 70 subjects enrolled , 60 completed the clinical trial . The 17 subjects receiving GH alone all completed the trial and reached a height of 150.4+/-5.5 cm ( mean + /- SD ) , 8.4+/-4.5 cm taller than their mean projected adult height at enrollment ( 95 % confidence interval [ CI ] : 6.3 to 10.6 cm ) . The 43 subjects receiving GH plus OX attained a mean height of 152.1+/-5.9 cm , 10.3+/-4.7 cm taller than their mean projected adult height ( 95 % CI : 8.9 to 11.7 cm ) . The historical control subjects had a mean adult height of 144.2+/-6.0 cm , precisely matching their original projected adult height of 144.2+/-6.1 cm . CONCLUSIONS GH , either alone or in combination with OX , is capable of stimulating short-term growth and augmenting adult height in girls with TS . With early diagnosis and 
    Output:
    
agent
Skeletal maturity was not accelerated by treatment with recombinant growth hormone ( hGH ) .
Adverse effects were minimally reported .
There is little evidence of serious short-term adverse effects in these trials , but they are underpowered to detect rare adverse effects .
REVIEW ER 'S CONCLUSIONS Recombinant human growth hormone ( hGH ) doses between 0.3 - 0.375 mg/kg/wk increase short-term growth in girls with Turner Syndrome ( TS ) by approximately 3 cm in the first year of treatment and by approximately 2 cm per year after 2 years of treatment .
There is little evidence on the effects of hGH on final height .
***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: Seventy girls with Turner syndrome , verified by karyotype , were r and omly assigned to observation or treatment with human growth hormone ( hGH ) , ox and rolone , or a combination of hGH plus ox and rolone for a period of 12 to 24 months , to assess the effect of treatment on growth velocity and adult height . Subsequently , all subjects received either hGH alone or hGH plus ox and rolone . Data are presented for 62 subjects treated for a period of 3 to 6 years . When compared with the anticipated growth rate in untreated patients , the growth rate after treatment with hGH , both alone and in combination with ox and rolone , showed a sustained increase for at least 6 years . Treatment is continuing in over half of the subjects ; at present , 14 ( 82 % ) of 17 girls receiving hGH alone and 41 ( 91 % ) of 45 girls receiving combination therapy exceeded their expected adult heights .  Thirty girls have completed treatment ; mean height for these 30 patients is 151.9 cm , compared with their mean original projected adult height of 143.8 cm . We conclude that therapy with hGH , alone and in combination with ox and rolone , can result in a sustained increase in growth rate and a significant increase in adult height for most prepubertal girls with Turner syndrome In 1983 , a multicenter , collaborative , prospect i ve study was begun to investigate the efficacy of human growth hormone ( hGH ) , alone and in combination with ox and rolone , in girls with Turner syndrome . While subjects in the control group grew 3.8 cm/yr ( -0.1 SD for untreated Turner patients ) , subjects receiving hGH alone  grew 6.6 , 5.4 and 4.6 cm/yr in years 1 - 3 , respectively ( + 3.1 , + 2.0 , + 1.4 SD ) . Subjects in the combination therapy group grew 9.8 , 7.4 and 6.1 cm/yr ( + 6.6 , + 4.3 , + 3.0 SD ) . Turner subjects in both treatment groups showed increased in Bayley-Pinneau predicted adult heights and in Turner projected adult heights Preliminary results are presented after 2 years of the Canadian long-term multicentre study on the impact of hormone therapy on the final height , sexual development and psychological status of girls with Turner syndrome . Girls entering the study were r and omized either to be treated with recombinant human growth hormone or to act as controls . Both groups received oestrogen replacement therapy in the same dose and format at the age of 13 years . However , for the purpose s of the psychological study at this time , children receiving oestrogen were excluded from analysis . Girls treated with GH for a period of 2 years showed a significant increase in growth rate , which declined with continued treatment , while the growth rate in the control group remained constant throughout . There was a correlation between the higher growth rate and the girls ' perceptions of themselves as more intelligent , more attractive , having more friends , greater popularity and experiencing less teasing than the untreated group . Growth rate was not correlated with family or school functioning STUDY OBJECTIVE To determine the influence of the injection frequency and the initial bone age on the efficacy of treatment with biosynthetic growth hormone in Turner 's syndrome . DESIGN R and omized study . SETTING Referral-based pediatric endocrinology departments of seven university medical centers . PATIENTS Fifty-two patients with Turner 's syndrome confirmed with chromosomal analysis . TREATMENT Somatotropin recombinant DNA ( 24 IU/m2 of body surface area ) subcutaneously administered in three or six injections per week for 2 years . Patients who were older than 12 years at the beginning of the study received low doses of estrogen . RESULTS The following statistically significant findings supported the use of six injections per week compared with three injections per week : the mean ( + /- SD ) increment in height during 2 years was 11.3 cm ( 3.8 cm ) with six injections vs 8.6 cm ( 3.4 cm ) with three injections ; the increment in height st and ard deviation score was 0.9 cm ( 0.5 cm ) vs 0.6 cm ( 0.3 cm ) ; the growth velocity was 6.6 cm/y ( 2.0 cm/y ) vs 5.2 cm/y ( 1.7 cm/y ) in year 1 and 4.7 cm/y ( 2.0 cm/y ) vs 3.4 cm/y ( 1.7 cm/y ) in year 2 ; and the increment in height st and ard deviation score for bone age was 0.8 cm ( 0.5 cm ) vs 0.4 cm ( 0.6 cm ) . For patients whose initial bone age was more than 13 years , growth velocity increased by 1 to 2 cm in year 1 ; in year 2 no increment was observed . We did not observe adverse effects . CONCLUSIONS Biosynthetic growth hormone in a higher-frequency regimen in Turner 's syndrome is more efficient in terms of increment in height , growth velocity , and height st and ard deviation score for bone age than treatment in a lower-frequency regimen . In patients with an initial bone age of more than 13 years , the response was poor . Longer follow-up is necessary to assess the effect on final height OBJECTIVES To study final height in girls with Turner ’s syndrome treated with once or twice daily injections of growth hormone ( GH ) in combination with low dose ethinyl oestradiol . DESIGN Until final height was reached , the effect of fractionated subcutaneous injections given twice daily was compared with once daily injections of a total GH dose of 6 IU/m2/day . Twice daily injections were given as one third in the morning and two thirds at bedtime . All girls concurrently received low dose oestradiol ( 0.05 μg ethinyl oestradiol/kg/day , increased to 0.10 μg/kg/day after 2.25 years ) . PATIENTS Nineteen girls with Turner ’s syndrome aged ⩾ 11 years ( mean ( SD ) 13.6 ( 1.7 ) years ) . MEASUREMENTS To determine final height gain , we assessed the difference between the attained final height and the final height predictions at the start of treatment . These final height predictions were calculated using the Bayley-Pinneau ( BP ) prediction method , the modified projected adult height ( mPAH ) , the modified index of potential height ( mIPHRUS ) , and the Turner ’s specific prediction method ( PTSRUS ) . RESULTS The gain in final height ( mean ( SD ) ) was not significantly different between the once daily and the twice daily regimens ( 7.6 ( 2.3 ) v 5.1 ( 3.2 ) cm ) . All girls exceeded their adult height prediction ( range , 1.6–12.3 cm ) . Thirteen of the 19 girls  had a final height gain > 5.0 cm . Mean ( SD ) attained final height was 155.5 ( 5.4 ) cm . A “ younger bone age ” at baseline and a higher increase in height st and ard deviation score for chronological age ( Dutch – Swedish – Danish references ) in the first year of GH treatment predicted a higher final height gain  after GH treatment . CONCLUSIONS Division of the total daily GH dose ( 6 IU/m2/day ) into two thirds in the evening and one third in the morning is not advantageous over the once daily GH regimen with respect to final height gain . Treatment with a GH dose of 6 IU/m2/day in combination with low dose oestrogens can result in a significant increase in adult height in girls with Turner ’s syndrome , even if they start GH treatment at a relatively late age Forty patients with Turner 's syndrome , aged 5.0 - 16.6 yr , were r and omly allocated to receive daily sc injections of recombinant human GH ( hGH ) at a dose of 1 IU/kg.week alone ( group I ) or in combination with 25 ng/kg.day ethinyl estradiol ( E2 ; group II ) . The mean pretreatment height velocity was 3.8 cm/yr for both groups . During the first year of treatment height velocity increased significantly ( P less than 0.001 ) in both groups , to 7.5 + /- 1.3 and 8.1 + /- 1.6 cm/yr , respectively . The difference between the two groups was not significant . The mean ( + /- SD ) height velocity expressed as the SD score for chronological age ( Turner references ) was 0.0 + /- 1.2 for group I and 0.2 + /- 1.4 for group II and increased significantly ( P less than 0.001 ) during the first year of treatment to + 4.3 + /- 1.1 in group I and + 5.4 + /- 1.2 in group II . The difference between both groups was statistically significant ( P less than 0.01 ) . Height SD score for chronological age ( Turner references ) increased from -0.2 + /- 0.9 to + 0.6 + /- 1.0 in group I and from -0.2 + /- 1.0 to + 0.7 + /- 1.1 in group II . Mean bone age progressed similarly in both treatment groups ( 1.1 + /- 0.6 yr during 1 yr of treatment ) . However , bone age maturation accelerated more rapidly in younger patients . Twelve girls ( three in group I and nine in group II ) had minor breast development . No major adverse effects were reported . We conclude that daily sc therapy with hGH stimulates height velocity in Turner 's syndrome . The beneficial effect on height velocity increment of E2 addition was small . Furthermore , even very low doses of E2 may induce breast development at an early age and accelerate bone maturation . For these reasons , the addition of E2 to hGH is not warranted in young patients with Turner 's syndrome 91 girls with Turner syndrome ( TS ) with a mean chronological age ( CA ) and bone age ( BA ) of 10.3 + /- 2.3 and 8.9 + /- 1.9 years , respectively , were r and omly assigned to subcutaneous treatment with recombinant human growth hormone ( rhGH ) alone ( n = 47 ) , 2.6 IU/m2 body surface area daily or combination treatment ( n = 44 ) with the same dose of rhGH and ox and rolone 0.1 mg/kg body weight orally , for the first 12 months of this study . During the 1st year of therapy , there was a striking increase in height velocity ( HV ) in both groups , from 4.0 + /- 0.8 to 6.3 + /- 1.3 cm/year [ HV st and ard ( st and ards of untreated Turner patients ) deviation score ( SDS ) for CA from 0.0 + /- 0.7 to 2.9 + /- 1.3 ] in the rhGH group and from 4.2 + /- 1.2 to 8.5 + 2- 1.7 cm/year ( HV SDS-CA from + 0.3 + /- 1.0 to 5.6 + /- 1.6 ) in the combination group . The difference between the groups was statistically significant ( p < 0.01 ) . During the 2nd year of treatment , the rhGH dose was increased to 3.4 IU/m2 daily for the rhGH-alone group , whereas in the combination treatment group the ox and rolone dose was reduced to 0.05 mg/kg daily . HV was maintained at significantly higher levels than those prior to treatment , at 5.3 + /- 1.1 cm/year ( HV SDS-CA : + 2.1 + /- 1.3 ) and 6.2 + /- 1.5 cm/year ( HV SDS-CA : + 3.6 + /- 1.4 ) in the rhGH-alone and the combination group , respectively ( p < 0.001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To carry out a multicenter , prospect i ve , r and omized trial of human growth hormone ( GH ) , alone or in combination with ox and rolone ( OX ) , in patients with Turner 's syndrome ( TS ) . METHODS In an initial phase lasting 12 to 24 months , 70 girls with TS , verified by karyotype , were r and omly assigned to one of four groups : ( 1 ) observation , ( 2 ) OX , ( 3 ) GH , or ( 4 ) GH plus OX . After completion of the first phase , group 3 subjects continued to receive GH only . All other subjects were treated with GH plus OX . Subjects were followed up until attainment of adult height and /or cessation of treatment . Data from this trial were compared with growth characteristics of 25 American historical subjects with TS ( matched for age , height , parental target height , and karyotype ) who never received either GH or and rogens .  RESULTS Of the 70 subjects enrolled , 60 completed the clinical trial . The 17 subjects receiving GH alone all completed the trial and reached a height of 150.4+/-5.5 cm ( mean + /- SD ) , 8.4+/-4.5 cm taller than their mean projected adult height at enrollment ( 95 % confidence interval [ CI ] : 6.3 to 10.6 cm ) . The 43 subjects receiving GH plus OX attained a mean height of 152.1+/-5.9 cm , 10.3+/-4.7 cm taller than their mean projected adult height ( 95 % CI : 8.9 to 11.7 cm ) . The historical control subjects had a mean adult height of 144.2+/-6.0 cm , precisely matching their original projected adult height of 144.2+/-6.1 cm . CONCLUSIONS GH , either alone or in combination with OX , is capable of stimulating short-term growth and augmenting adult height in girls with TS . With early diagnosis and 
    Output:
    