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: A population -based cohort study was done to estimate the incidence of different types of injuries and to evaluate certain risk factors in an urban slum ; 4333 slum dwellers in Madras city in India were r and omly selected by cluster sampling  , of whom 1.7 per cent were lost during the 12 months of follow up . The cumulative injury incidence for 12 months for all injuries was 127 per 1000 persons ( 95 per cent confidence interval 117 - 137 ) ; for males 137 per 1000 and for females 118 per 1000 . Incidence of unintentional injury was 121 per 1000 persons . The incidence for road traffic injury was 16 per 1000 persons , for household injuries 57 per 1000 persons and for injury at place of work 19 per 1000 persons . The relative risk of males to females for traffic injuries was 3.04 and for household injuries was 0.39 . The relative risk of traffic injuries among adult males who reported daily alcohol consumption was 2.26 . The incidence of injury is high in an urban slum and it is a priority health problem . This study has identified groups of people who are at high risk for injuries and who may need specific protective measures This pilot aims to better underst and the market for childcare in Saudi Arabia – both the supply and dem and sides – and to design a r and omized controlled experiment to test whether access to affordable day care ( in the form of subsidies , for example ) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired . In addition , the study seeks to underst and the degree to which employment early on in one ’s life impacts employment in later stages . The pilot will provide information on the groups of women the experiment should target , appropriate levels for the childcare subsidy , and the quality and current geographic locations of daycare sites . Expected Impact Determine the effects of facilitating childcare access on Saudi women ’s employment . PRINCIPAL INVESTIGATORS  Boston University Patricia Cortes  Harvard University Claudia Goldin  Swarthmore College Jennifer It is desirable that young women with primary ovarian failure achieve normal peak bone mass to reduce the subsequent risk of osteoporosis , and that there are management strategies to replace bone that is already lost . While estrogen ( E2 ) is generally considered to prevent bone loss by suppressing bone resorption , it is now recognized that estrogen also exerts an anabolic effect on the human skeleton . In this study , we tested whether estrogen could increase bone mass in women with primary ovarian failure . We studied the mechanism underlying this by analyzing biochemical markers of bone turnover and iliac crest biopsy specimens obtained before and 3 years after E2 replacement .  Twenty-one women with Turner 's syndrome , aged 20 - 40 years , were studied . The T scores of bone mineral density at lumbar spine and proximal femur at baseline were -1.4 and -1.1 , respectively . Hormone replacement was given as subcutaneous E2 implants ( 50 mg every 6 months ) with oral medroxy progesterone .  Serum E2 levels increased incrementally from 87.5 pM at baseline to 323 , 506 , 647 , and 713 pM after 6 months and 1 , 2 , and 3 years of hormone replacement therapy ( HRT ) , respectively . The bone mineral density at the lumbar spine and proximal femur increased after 3 years to T scores of -0.2 and -0.4 , respectively . The cancellous bone volume increased significantly from 13.4 % to 18.8 % . There was a decrease in activation frequency , but the active formation period was increased by HRT . There was a significant increase in the wall thickness from 33.4 microm at baseline to 40.9 microm after 3 years of HRT , reflecting an increase in bone formed at individual remodeling units . Although there was an early increase in biochemical markers of bone formation , these declined thereafter . Our results show that estrogen is capable of exerting an anabolic effect in the skeleton of young women with Turner 's syndrome and low bone mass The aim of the present study was to examine the impact of sequential change in the route of estrogen administration on body composition and insulin resistance in patients with Turner syndrome ( TS ) using  cyclical hormone replacement therapy ( HRT ) with conjugated equine estrogens ( CEE ) plus medroxyprogesterone acetate ( MPA ) . We carried out a self-controlled study of nine non-obese patients with TS , with an average age of 23 ± 4.9 years .  Body mass index ( BMI ) , waist-to-hip ratio ( WHR ) , fasting glycemia , insulin tolerance ( glucose disappearance constant during an insulin tolerance test , kITT ) and body composition ( dual-energy X-ray absorptiometry ) were studied after 1 year 's use of CEE plus MPA and repeated after 1 year 's use of 17β-estradiol gel with the same schedule of MPA administration . We did not observe any difference between the oral and percutaneous HRT with regard to BMI , WHR and insulin tolerance ( kITT : 4.9 ± 1.5 vs. 5.3 ± 1.5%/min , p = 0.8 ) . During administration of the 17β-estradiol gel a tendency to increased total lean mass ( p = 0.054 ) was observed . We conclude that sequential change in the route of estrogen administration in TS patients using cyclical HRT with CEE and MPA does not affect insulin resistance , although use of percutaneous 17β-estradiol gel seems to exert favorable changes in body composition Background There are limited long-term r and omized controlled trials of growth hormone ( GH ) supplementation to adult height and few published reports of the health-related quality of life ( HRQOL ) following treatment . The present follow-up study of young adults from a long-term controlled trial of GH treatment in patients with Turner syndrome ( TS ) yielded data to examine whether GH supplementation result ed in a higher HRQOL ( either due to taller stature or from the knowledge that active treatment and not placebo had been received ) or alternatively a lower HRQOL ( due to medicalization from years of injections ) . Methods The original trial r and omized 154 Canadian girls with TS aged 7 - 13 years from 13 centres to receive either long-term GH injections at the pharmacologic dose of 0.3 mg/kg/week or to receive no injections ; estrogen prescription for induction of puberty was st and ardized . Patients were eligible for the follow-up study if they were at least 16 years old at the time of follow-up . The instrument used to study HRQOL was the SF-36 , summarized into physical and mental component scales ( PCS and MCS ) ; higher scores indicate better HRQOL . Results Thirty-four of the 48 eligible participants ( 71 % ) consented to participate ; data were missing for one patient . Both groups ( GH and no treatment ) had normal HRQOL at this post-treatment assessment . The GH group had a ( mean ± SD ) PCS score of 56 ± 5 ; the untreated group 58 ± 4 ; mean score for 16 - 24 year old females in the general population 53.5 ± 6.9 . The GH group had a mean MCS score of 52 ± 6 ; the untreated group 49 ± 13 ; mean score for 16 - 24 year old females in the general population 49.6 ± 9.8 . Secondary analyses showed no relationship between HRQOL and height . Conclusions We found no benefit or adverse effect on HRQOL either from receiving or not receiving growth hormone injections in a long-term r and omized controlled trial , confirming larger observational studies . We suggest that it remains ethically acceptable as well as necessary to maintain a long-term untreated control group to estimate the effects of pharmacological agents to manipulate adult height . Young adult women with TS have normal HRQOL suggesting that they adjust well to their challenges in life . Trial Registration Clinical Trials.gov Identifier NCT00191113 OBJECTIVE To determine whether young women with Turner 's syndrome who had normal bone mineral density ( BMD ) before the induction of puberty maintain normal BMD in young adulthood . DESIGN Controlled clinical study . SETTING A private hospital clinical research setting . PATIENTS Young women with Turner 's syndrome in Tanner stage V of puberty with previously normal BMD . INTERVENTIONS Oral conjugated estrogens and progesterone acetate were administered continuously for a mean ( + /-SD ) of 4.1+/-1.0 years . Bone mineral densities and blood sample s were evaluated . MAIN OUTCOME MEASURE(S ) The BMD of the lumbar spine and the femoral neck was determined during young adulthood . The change in BMD over the previous 6 years also was evaluated . Serum concentrations of the carboxy-terminal propeptide of type 1 collagen and of the carboxy-terminal cross-linked telopeptide of type 1 collagen were measured . RESULT ( S ) The BMD of the lumbar spine was reduced significantly in our patients . There was no change in the BMD of the femoral neck or lumbar spine over a period of 6.1 years . Concentrations of the carboxy-terminal propeptide of type 1 collagen were decreased , whereas concentrations of the carboxy-terminal cross-linked telopeptide of type 1 collagen were increased . CONCLUSION ( S ) Young women with Turner 's syndrome do not attain normal peak bone mass even when estrogen replacement therapy is begun in adolescence . Their low BMD seems to be due to decreased bone formation and increased bone resorption Background Adolescent females with ovarian failure require estrogen therapy for induction of puberty and other important physiologic effects . Currently , health care providers have varying practice s without evidence -based st and ards , thus investigating potential differences between oral and transdermal preparations is essential . The purpose of this study was to compare the differential effects of treatment with oral conjugated equine estrogen ( OCEE ) , oral 17β estradiol ( OBE ) , or transdermal 17β estradiol ( TBE ) on biochemical profiles and feminization in girls with ovarian failure . Study design 20 prepubertal adolescent females with ovarian failure , ages 12–18 years , were r and omized to OCEE ( n = 8) , OBE ( n = 7 ) , or TBE ( n = 5 ) for 24 months .  Estrogen replacement was initiated at a low dose ( 0.15 mg OCEE , 0.25 mg OBE , or 0.0125 mg TBE ) and doubled every 6 months to a maximum dose of 0.625 mg/d OCEE , 1 mg/d OBE , or 0.05 mg/d TBE . At 18 months , micronized progesterone was added to induce menstrual cycles . Biochemical markers including sex hormones , inflammatory markers , liver enzymes , coagulation factors , and lipids were obtained at baseline and 6 month intervals . Differences in levels of treatment parameters between the groups were evaluated with one-way analysis of variance ( ANOVA ) . The effect of progesterone on biochemical markers was evaluated with the paired t-test . Results Mean ( ±SE ) estradiol levels at maximum estrogen dose ( 18 months ) were higher in the TBE group ( 53 ± 19 pg/mL ) compared to OCEE ( 14 ± 5 pg/mL ) and OBE ( 12 ± 5 pg/mL ) ( p ≤ 0.01 ) . The TBE and OBE groups had more effective feminization ( 100 % Tanner 3 breast stage at 18 months ) . There were no statistical differences in other biochemical markers between treatment groups at 18 months or after the introduction of progesterone . Conclusions Treatment with transdermal 17β estradiol result ed in higher estradiol levels and more effective feminization compared to oral conjugated equine estrogen but did not result in an otherwise different biochemical profile in this limited number of heterogeneous patients . OBE and TBE provide safe and effective alternatives to OCEE to induce puberty in girls , but larger prospect i ve r and omized trials are required . Trial registration Clinical Trials Identifier : NCT01023178 Eight girls with Turner 's syndrome were given low dose oral ethinyl estradiol or transdermal 17 beta-estradiol in order to compare the effect of the route of administration on selected markers of hepatic metabolism , and various hormonal concentrations . Oral estrogen was given at a dose of 100 ng/kg/day and transdermal estrogen via adhesive skin patch at 0.0125 mg/kg/day . The subjects received one form of estradiol for one month , and after a one month washout period , received the other form . Both oral and transdermal estradiol caused a significant decrease in FSH while only transdermal result ed in a significant decrease in LH . Oral estradiol , though not transdermal estradiol , increased serum high density lipoprotein , thyroxine binding protein and growth hormone binding protein . Urinary growth hormone excretion increased after both forms of therapy , while insulin-like growth factor-I and insulin-like growth factor binding protein-3 remained unchanged . Thus , in girls with Turner 's syndrome , estrogen replacement by the transdermal route may have less deleterious effect on hepatic metabolism than oral est 
    Output:
    
agent
Using r and om-effects models , estrogen replacement therapy showed an increase in bone mineral density [ weighted mean change from baseline 0.09 g/cm2 ( 0.04–0.14 ) ] that differed by type of estrogen but not route of administration .
Oral estrogen replacement therapy showed a higher increase in high density lipoprotein cholesterol levels when compared to transdermal [ weighted mean difference 9.33 mg/dl ( 4.82–13.85 ) ] with no significant effect on other lipid fractions .
The current evidence suggests possible benefit of estrogen replacement therapy  on bone mineral density and high density lipoprotein cholesterol .
***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: A population -based cohort study was done to estimate the incidence of different types of injuries and to evaluate certain risk factors in an urban slum ; 4333 slum dwellers in Madras city in India were r and omly selected by cluster sampling  , of whom 1.7 per cent were lost during the 12 months of follow up . The cumulative injury incidence for 12 months for all injuries was 127 per 1000 persons ( 95 per cent confidence interval 117 - 137 ) ; for males 137 per 1000 and for females 118 per 1000 . Incidence of unintentional injury was 121 per 1000 persons . The incidence for road traffic injury was 16 per 1000 persons , for household injuries 57 per 1000 persons and for injury at place of work 19 per 1000 persons . The relative risk of males to females for traffic injuries was 3.04 and for household injuries was 0.39 . The relative risk of traffic injuries among adult males who reported daily alcohol consumption was 2.26 . The incidence of injury is high in an urban slum and it is a priority health problem . This study has identified groups of people who are at high risk for injuries and who may need specific protective measures This pilot aims to better underst and the market for childcare in Saudi Arabia – both the supply and dem and sides – and to design a r and omized controlled experiment to test whether access to affordable day care ( in the form of subsidies , for example ) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired . In addition , the study seeks to underst and the degree to which employment early on in one ’s life impacts employment in later stages . The pilot will provide information on the groups of women the experiment should target , appropriate levels for the childcare subsidy , and the quality and current geographic locations of daycare sites . Expected Impact Determine the effects of facilitating childcare access on Saudi women ’s employment . PRINCIPAL INVESTIGATORS  Boston University Patricia Cortes  Harvard University Claudia Goldin  Swarthmore College Jennifer It is desirable that young women with primary ovarian failure achieve normal peak bone mass to reduce the subsequent risk of osteoporosis , and that there are management strategies to replace bone that is already lost . While estrogen ( E2 ) is generally considered to prevent bone loss by suppressing bone resorption , it is now recognized that estrogen also exerts an anabolic effect on the human skeleton . In this study , we tested whether estrogen could increase bone mass in women with primary ovarian failure . We studied the mechanism underlying this by analyzing biochemical markers of bone turnover and iliac crest biopsy specimens obtained before and 3 years after E2 replacement .  Twenty-one women with Turner 's syndrome , aged 20 - 40 years , were studied . The T scores of bone mineral density at lumbar spine and proximal femur at baseline were -1.4 and -1.1 , respectively . Hormone replacement was given as subcutaneous E2 implants ( 50 mg every 6 months ) with oral medroxy progesterone .  Serum E2 levels increased incrementally from 87.5 pM at baseline to 323 , 506 , 647 , and 713 pM after 6 months and 1 , 2 , and 3 years of hormone replacement therapy ( HRT ) , respectively . The bone mineral density at the lumbar spine and proximal femur increased after 3 years to T scores of -0.2 and -0.4 , respectively . The cancellous bone volume increased significantly from 13.4 % to 18.8 % . There was a decrease in activation frequency , but the active formation period was increased by HRT . There was a significant increase in the wall thickness from 33.4 microm at baseline to 40.9 microm after 3 years of HRT , reflecting an increase in bone formed at individual remodeling units . Although there was an early increase in biochemical markers of bone formation , these declined thereafter . Our results show that estrogen is capable of exerting an anabolic effect in the skeleton of young women with Turner 's syndrome and low bone mass The aim of the present study was to examine the impact of sequential change in the route of estrogen administration on body composition and insulin resistance in patients with Turner syndrome ( TS ) using  cyclical hormone replacement therapy ( HRT ) with conjugated equine estrogens ( CEE ) plus medroxyprogesterone acetate ( MPA ) . We carried out a self-controlled study of nine non-obese patients with TS , with an average age of 23 ± 4.9 years .  Body mass index ( BMI ) , waist-to-hip ratio ( WHR ) , fasting glycemia , insulin tolerance ( glucose disappearance constant during an insulin tolerance test , kITT ) and body composition ( dual-energy X-ray absorptiometry ) were studied after 1 year 's use of CEE plus MPA and repeated after 1 year 's use of 17β-estradiol gel with the same schedule of MPA administration . We did not observe any difference between the oral and percutaneous HRT with regard to BMI , WHR and insulin tolerance ( kITT : 4.9 ± 1.5 vs. 5.3 ± 1.5%/min , p = 0.8 ) . During administration of the 17β-estradiol gel a tendency to increased total lean mass ( p = 0.054 ) was observed . We conclude that sequential change in the route of estrogen administration in TS patients using cyclical HRT with CEE and MPA does not affect insulin resistance , although use of percutaneous 17β-estradiol gel seems to exert favorable changes in body composition Background There are limited long-term r and omized controlled trials of growth hormone ( GH ) supplementation to adult height and few published reports of the health-related quality of life ( HRQOL ) following treatment . The present follow-up study of young adults from a long-term controlled trial of GH treatment in patients with Turner syndrome ( TS ) yielded data to examine whether GH supplementation result ed in a higher HRQOL ( either due to taller stature or from the knowledge that active treatment and not placebo had been received ) or alternatively a lower HRQOL ( due to medicalization from years of injections ) . Methods The original trial r and omized 154 Canadian girls with TS aged 7 - 13 years from 13 centres to receive either long-term GH injections at the pharmacologic dose of 0.3 mg/kg/week or to receive no injections ; estrogen prescription for induction of puberty was st and ardized . Patients were eligible for the follow-up study if they were at least 16 years old at the time of follow-up . The instrument used to study HRQOL was the SF-36 , summarized into physical and mental component scales ( PCS and MCS ) ; higher scores indicate better HRQOL . Results Thirty-four of the 48 eligible participants ( 71 % ) consented to participate ; data were missing for one patient . Both groups ( GH and no treatment ) had normal HRQOL at this post-treatment assessment . The GH group had a ( mean ± SD ) PCS score of 56 ± 5 ; the untreated group 58 ± 4 ; mean score for 16 - 24 year old females in the general population 53.5 ± 6.9 . The GH group had a mean MCS score of 52 ± 6 ; the untreated group 49 ± 13 ; mean score for 16 - 24 year old females in the general population 49.6 ± 9.8 . Secondary analyses showed no relationship between HRQOL and height . Conclusions We found no benefit or adverse effect on HRQOL either from receiving or not receiving growth hormone injections in a long-term r and omized controlled trial , confirming larger observational studies . We suggest that it remains ethically acceptable as well as necessary to maintain a long-term untreated control group to estimate the effects of pharmacological agents to manipulate adult height . Young adult women with TS have normal HRQOL suggesting that they adjust well to their challenges in life . Trial Registration Clinical Trials.gov Identifier NCT00191113 OBJECTIVE To determine whether young women with Turner 's syndrome who had normal bone mineral density ( BMD ) before the induction of puberty maintain normal BMD in young adulthood . DESIGN Controlled clinical study . SETTING A private hospital clinical research setting . PATIENTS Young women with Turner 's syndrome in Tanner stage V of puberty with previously normal BMD . INTERVENTIONS Oral conjugated estrogens and progesterone acetate were administered continuously for a mean ( + /-SD ) of 4.1+/-1.0 years . Bone mineral densities and blood sample s were evaluated . MAIN OUTCOME MEASURE(S ) The BMD of the lumbar spine and the femoral neck was determined during young adulthood . The change in BMD over the previous 6 years also was evaluated . Serum concentrations of the carboxy-terminal propeptide of type 1 collagen and of the carboxy-terminal cross-linked telopeptide of type 1 collagen were measured . RESULT ( S ) The BMD of the lumbar spine was reduced significantly in our patients . There was no change in the BMD of the femoral neck or lumbar spine over a period of 6.1 years . Concentrations of the carboxy-terminal propeptide of type 1 collagen were decreased , whereas concentrations of the carboxy-terminal cross-linked telopeptide of type 1 collagen were increased . CONCLUSION ( S ) Young women with Turner 's syndrome do not attain normal peak bone mass even when estrogen replacement therapy is begun in adolescence . Their low BMD seems to be due to decreased bone formation and increased bone resorption Background Adolescent females with ovarian failure require estrogen therapy for induction of puberty and other important physiologic effects . Currently , health care providers have varying practice s without evidence -based st and ards , thus investigating potential differences between oral and transdermal preparations is essential . The purpose of this study was to compare the differential effects of treatment with oral conjugated equine estrogen ( OCEE ) , oral 17β estradiol ( OBE ) , or transdermal 17β estradiol ( TBE ) on biochemical profiles and feminization in girls with ovarian failure . Study design 20 prepubertal adolescent females with ovarian failure , ages 12–18 years , were r and omized to OCEE ( n = 8) , OBE ( n = 7 ) , or TBE ( n = 5 ) for 24 months .  Estrogen replacement was initiated at a low dose ( 0.15 mg OCEE , 0.25 mg OBE , or 0.0125 mg TBE ) and doubled every 6 months to a maximum dose of 0.625 mg/d OCEE , 1 mg/d OBE , or 0.05 mg/d TBE . At 18 months , micronized progesterone was added to induce menstrual cycles . Biochemical markers including sex hormones , inflammatory markers , liver enzymes , coagulation factors , and lipids were obtained at baseline and 6 month intervals . Differences in levels of treatment parameters between the groups were evaluated with one-way analysis of variance ( ANOVA ) . The effect of progesterone on biochemical markers was evaluated with the paired t-test . Results Mean ( ±SE ) estradiol levels at maximum estrogen dose ( 18 months ) were higher in the TBE group ( 53 ± 19 pg/mL ) compared to OCEE ( 14 ± 5 pg/mL ) and OBE ( 12 ± 5 pg/mL ) ( p ≤ 0.01 ) . The TBE and OBE groups had more effective feminization ( 100 % Tanner 3 breast stage at 18 months ) . There were no statistical differences in other biochemical markers between treatment groups at 18 months or after the introduction of progesterone . Conclusions Treatment with transdermal 17β estradiol result ed in higher estradiol levels and more effective feminization compared to oral conjugated equine estrogen but did not result in an otherwise different biochemical profile in this limited number of heterogeneous patients . OBE and TBE provide safe and effective alternatives to OCEE to induce puberty in girls , but larger prospect i ve r and omized trials are required . Trial registration Clinical Trials Identifier : NCT01023178 Eight girls with Turner 's syndrome were given low dose oral ethinyl estradiol or transdermal 17 beta-estradiol in order to compare the effect of the route of administration on selected markers of hepatic metabolism , and various hormonal concentrations . Oral estrogen was given at a dose of 100 ng/kg/day and transdermal estrogen via adhesive skin patch at 0.0125 mg/kg/day . The subjects received one form of estradiol for one month , and after a one month washout period , received the other form . Both oral and transdermal estradiol caused a significant decrease in FSH while only transdermal result ed in a significant decrease in LH . Oral estradiol , though not transdermal estradiol , increased serum high density lipoprotein , thyroxine binding protein and growth hormone binding protein . Urinary growth hormone excretion increased after both forms of therapy , while insulin-like growth factor-I and insulin-like growth factor binding protein-3 remained unchanged . Thus , in girls with Turner 's syndrome , estrogen replacement by the transdermal route may have less deleterious effect on hepatic metabolism than oral est 
    Output:
    