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: PURPOSE The purpose of the article was to examine the association of early life growth with age at menarche . METHODS Using data from a prospect i ve birth cohort ( n = 1134 women , 290 sibling sets ) , we assessed the association between postnatal growth at 4 months , 1 year , and 4 years and age at menarche , using generalized estimating equations and generalized linear r and om effects models . RESULTS Overall , 18 % of the cohort experienced early menarche ( < 12 years ) . After accounting for postnatal growth in length , faster postnatal change in weight ( per 10-percentile increase ) in all three periods was associated with an increase ( range 9%-20 % ) in the likelihood of having an early menarche . In adjusted linear models , faster weight gains in infancy and childhood were associated with an average age at menarche that was 1.1 - 1.3 months earlier compared with stable growth . The overall results were consistent for percentile and conditional growth models . Girls who experienced rapid growth ( defined as increasing across two major Centers for Disease Control and Prevention growth percentiles ) in early infancy had an average age at menarche that was 4.6 months earlier than girls whose growth was stable . CONCLUSIONS Faster postnatal weight gains in infancy and early childhood before the age of 4 years are associated with earlier age at menarche Background : Given global trends toward earlier onset of puberty and the adverse psychosocial consequences of early puberty , it is important to underst and the childhood predictors of pubertal timing and tempo . Objective : We examined the association between early growth and the timing and tempo of puberty in adolescents in South Africa . Methods : We analyzed prospect ively collected data from 1060 boys and 1135 girls participating in the Birth-to-Twenty cohort in Soweto , South Africa .  Height-for-age z scores ( HAZs ) and body mass index – for-age z scores ( BMI Zs ) were calculated based on height ( centimeters ) and body mass index ( kilograms per meter squared ) at ages 5 y and 8 y. The development of genitals , breasts , and pubic hair was recorded annually from 9 to 16 y of age with the use of the Tanner sexual maturation scale ( SMS ) . We used latent class growth analysis to identify pubertal trajectory classes and also characterized children as fast or slow developers based on the SMS score at 12 y of age . We used multinomial logistic regression to estimate associations of HAZ and BMI Z at ages 5 and 8 y with pubertal development . Results : We identified 3 classes for pubic hair development ( for both girls and boys ) and 4 classes for breast ( for girls ) and genital ( for boys ) development . In girls , both HAZ and BMI Z at age 5 y were positively associated with pubic hair development [ relative risk ratio ( RRR ) : 1.57 , P < 0.001 and RRR : 1.51 , P < 0.01 , respectively ] , as was BMI at age 8 y ( RRR : 2.06 , P = 0.03 ) ; similar findings were observed for breast development . In boys , HAZ and BMI Z at age 5 y were positively associated with pubic hair development ( RRR : 1.78 , P < 0.001 and RRR : 1.43 , P < 0.01 , respectively ) ; HAZ at age 5 y was associated with development of genitals ( RRR : 2.19 , P < 0.01 ) . Conclusion : In boys and girls , both height and body mass index in early childhood predicted the trajectory of pubertal development . This may provide a tool to identify children at risk of early pubertal onset OBJECTIVE The objective of this study was to determine the influence of  birth weight and postnatal weight gain  on age at menarche . DESIGN , SETTING , AND PARTICIPANTS This was a prospect i ve cohort study where girls from the West Australian Pregnancy ( Raine ) Cohort Study were followed prospect ively from fetal life ( 18 wk of pregnancy ) to adolescence ( 12 - 14 yr ) . MAIN OUTCOME MEASURE Age at menarche was the main outcome measure . RESULTS Growth status at birth was judged by expected birth weight ratio ( EBW ; a ratio of observed infant 's birth weight over median birth weight appropriate for maternal age , weight , height , parity , infant sex , and gestational age ) . Postnatal growth status was judged by body mass index ( BMI ) . Both EBW ( P = 0.020 ) and BMI in childhood ( 8 yr of age ) ( P < 0.001 ) were associated with age at menarche . Menarche occurred earlier in girls with lower EBW and higher BMI . CONCLUSIONS We have demonstrated for the first time that both birth weight and weight gain in childhood are associated with age at menarche . Weight gain before birth and subsequent weight gain up to the age of 8 yr were found to have opposing influences on the timing of menarche . Lower EBW combined with higher BMI during childhood predicted early age at menarche , and this relationship existed across normal birth weight and BMI ranges Aims /hypothesisEarlier age at menarche is associated with increased BMI and obesity risk from early childhood through to adulthood . We hypothesised that earlier age at menarche would also predict subsequent diabetes risk . Methods This was a population -based prospect i ve cohort study of 13,308 women , who were aged 40 to 75 years between 1993 and 1997 and participating in the Norfolk cohort of the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC-Norfolk ) . We used data on age at menarche and ascertained diabetes incidence to 2005 . Results There were 734 cases of diabetes ( 363 incident and 371 prevalent cases ) . Mean age at menarche was lower in women with diabetes than in non-diabetic women ( 12.8 vs 13.0 years , p = 0.008 ) . Compared with the earliest quintile ( menarche at 8–11 years ) , women in the oldest quintile ( menarche at 15–18 years ) had lower BMI ( 25.5 vs 27.4 kg/m2 , p < 0.0001 ) and a reduced risk of diabetes ( OR 0.66 [ 95 % CI 0.51–0.86 ] adjusted for age , family history , physical activity , smoking , occupational social class , parity and use of hormonal preparations ) . The association between age at menarche and diabetes was linear ( adjusted OR 0.91 [ 95 % CI 0.87–0.96 ] per 1 year later menarche ) and appeared to be completely mediated by adult BMI or waist circumference ( OR 0.98 [ 95 % CI 0.93–1.03 ] , further adjusted for BMI at age 40–75 years ) . Conclusions /interpretationEarlier age at menarche increases the risk of diabetes in women and this association appears to be mediated by increased adiposity . History of earlier menarche may help to identify women with increased subsequent risk of diabetes Background Lack of appropriate reporting of method ological details has previously been shown to distort risk of bias assessment s in r and omized controlled trials . The same might be true for observational studies . The goal of this study was to compare the Newcastle-Ottawa Scale ( NOS ) assessment for risk of bias between review ers and authors of cohort studies included in a published systematic review on risk factors for severe outcomes in patients infected with influenza . Methods Cohort studies included in the systematic review and published between 2008–2011 were included . The corresponding or first authors completed a survey covering all NOS items . Results were compared with the NOS assessment applied by review ers of the systematic review . Inter-rater reliability was calculated using kappa ( K ) statistics . Results Authors of 65/182 ( 36 % ) studies completed the survey . The overall NOS score was significantly higher ( p < 0.001 ) in the review ers ’ assessment ( median = 6 ; interquartile range [ IQR ] 6–6 ) compared with those by authors ( median = 5 , IQR 4–6 ) . Inter-rater reliability by item ranged from slight ( K = 0.15 , 95 % confidence interval [ CI ] = −0.19 , 0.48 ) to poor ( K = −0.06 , 95 % CI = −0.22 , 0.10 ) . Reliability for the overall score was poor ( K = −0.004 , 95 % CI = −0.11 , 0.11 ) . Conclusions Differences in assessment and low agreement between review ers and authors suggest the need to contact authors for information not published in studies when applying the NOS in systematic review CONTEXT Adult women with polycystic ovary syndrome ( PCOS ) have decreased GnRH pulse generator sensitivity to progesterone (P)-mediated slowing . This defect is and rogen mediated because it is reversed with and rogen receptor blockade . Adolescent hyper and rogenism often precedes PCOS . OBJECTIVE The aim of the study was to evaluate GnRH pulse generator sensitivity to P-mediated slowing in normal and hyper and rogenic girls . DESIGN We conducted a controlled interventional study . SETTING The study was conducted in a general clinical research center . PARTICIPANTS A total of 26 normal control ( NC ) and 26 hyper and rogenic ( HA ) girls were studied . INTERVENTION Frequent blood sampling was performed for 11 h to assess LH pulse frequency before and after 7 d of oral estradiol and P. MAIN OUTCOME MEASURE We measured the slope of the percentage reduction in LH pulse frequency as a function of d 7 P ( slope ) . RESULTS Overall , Tanner 3 - 5 HA subjects were less sensitive to P-mediated slowing than Tanner 3 - 5 NC ( slope , 4.7 + /- 3.4 vs. 10.3 + /- 7.7 ; P = 0.006 ) . However , there was variability in the responses of HA subjects ; 15 had P sensitivities within the range seen in NC , whereas nine were relatively P insensitive . The two groups had similar testosterone levels . Fasting insulin levels were higher in P-insensitive HA girls ( 39.6 + /- 30.6 vs. 22.2 + /- 13.9 microIU/ml ; P = 0.02 ) , and there was an inverse relationship between fasting insulin and P sensitivity in HA girls ( P = 0.02 ) . Tanner 1 - 2 NC had lower testosterone levels and were more P sensitive than Tanner 3 - 5 NC ( slope , 19.3 + /- 5.8 ; P = 0.04 ) . CONCLUSIONS Hyper and rogenism is variably associated with reduced GnRH pulse generator sensitivity to P-mediated slowing during adolescence . In addition to and rogen levels , insulin resistance may modulate P sensitivity CONTEXT Rapid postnatal weight gain has been associated with subsequent increased childhood adiposity . However , the contribution of rapid weight gain during specific infancy periods is not clear . OBJECTIVE We aim ed to determine which periods of infancy weight gain are related to childhood adiposity and also to age at menarche in UK girls . DESIGN , SETTING , AND PARTICIPANTS A total of 2715 girls from a prospect i ve UK birth cohort study participated in the study . MAIN OUTCOME MEASURES Routinely measured weights and lengths at ages 2 , 9 , and 19 months were extracted from the local child health computer data base . Body composition was assessed by dual-energy x-ray absorptiometry at age 10 yr , and age at menarche was assessed by question naire ( categorized into three groups : < 12.0 , 12.0 - 13.0 , and > 13.0 yr ) . RESULTS Faster early infancy weight gain between 0 and 2 months and also 2 to 9 months were associated with increased body fat mass relative to lean mass at age 10 yr and also with earlier age at menarche . Each + 1 unit gain in weight sd score between 0 and 9 months was associated with an odds ratio ( 95 % confidence interval ) = 1.48 ( 1.27 - 1.60 ) for overweight ( body mass index > 85th centile ) at 10 yr , and 1.34 ( 1.21 - 1.49 ) for menarche at less than 12 yr . In contrast , subsequent weight gain between 9 and 19 months was not associated with later adiposity or age at menarche . CONCLUSIONS In developed setting s , rapid weight gain during the first 9 months of life is a risk factor for both increased  childhood adiposity and early menarche in girls STUDY OBJECTIVE To analyze age at menarche and its association with excess weight and body fat percentage . DESIGN School-based cross-sectional survey . SETTING Southwestern region of the Brazilian Amazon . PARTICIPANTS The sample was made up of 727 girls , in the 8- to 16-year age range , divided into 3 groups : early , normal , and late menarche , from public and private schools , selected through proportional stratified r and om sampling . INTERVENTIONS AND MAIN OUTCOME MEASURES  Bioimpedance  was used to  measure body fat percentage and body mass index , applying the Global School-Based Student Health Survey question naire to categorize behavior variables . Age at menarche was determined using the status quo method . Sexual maturity was assessed through self- assessment according to criteria described by Tanner . RESULTS Overall age at menarche was 11. 
    Output:
    
agent
There is no consistent result in the relationship between obesity and timing of pubertal onset in boys .
Obesity may contribute to early onset of puberty in girls , while in boys , there is insufficient data .
***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: PURPOSE The purpose of the article was to examine the association of early life growth with age at menarche . METHODS Using data from a prospect i ve birth cohort ( n = 1134 women , 290 sibling sets ) , we assessed the association between postnatal growth at 4 months , 1 year , and 4 years and age at menarche , using generalized estimating equations and generalized linear r and om effects models . RESULTS Overall , 18 % of the cohort experienced early menarche ( < 12 years ) . After accounting for postnatal growth in length , faster postnatal change in weight ( per 10-percentile increase ) in all three periods was associated with an increase ( range 9%-20 % ) in the likelihood of having an early menarche . In adjusted linear models , faster weight gains in infancy and childhood were associated with an average age at menarche that was 1.1 - 1.3 months earlier compared with stable growth . The overall results were consistent for percentile and conditional growth models . Girls who experienced rapid growth ( defined as increasing across two major Centers for Disease Control and Prevention growth percentiles ) in early infancy had an average age at menarche that was 4.6 months earlier than girls whose growth was stable . CONCLUSIONS Faster postnatal weight gains in infancy and early childhood before the age of 4 years are associated with earlier age at menarche Background : Given global trends toward earlier onset of puberty and the adverse psychosocial consequences of early puberty , it is important to underst and the childhood predictors of pubertal timing and tempo . Objective : We examined the association between early growth and the timing and tempo of puberty in adolescents in South Africa . Methods : We analyzed prospect ively collected data from 1060 boys and 1135 girls participating in the Birth-to-Twenty cohort in Soweto , South Africa .  Height-for-age z scores ( HAZs ) and body mass index – for-age z scores ( BMI Zs ) were calculated based on height ( centimeters ) and body mass index ( kilograms per meter squared ) at ages 5 y and 8 y. The development of genitals , breasts , and pubic hair was recorded annually from 9 to 16 y of age with the use of the Tanner sexual maturation scale ( SMS ) . We used latent class growth analysis to identify pubertal trajectory classes and also characterized children as fast or slow developers based on the SMS score at 12 y of age . We used multinomial logistic regression to estimate associations of HAZ and BMI Z at ages 5 and 8 y with pubertal development . Results : We identified 3 classes for pubic hair development ( for both girls and boys ) and 4 classes for breast ( for girls ) and genital ( for boys ) development . In girls , both HAZ and BMI Z at age 5 y were positively associated with pubic hair development [ relative risk ratio ( RRR ) : 1.57 , P < 0.001 and RRR : 1.51 , P < 0.01 , respectively ] , as was BMI at age 8 y ( RRR : 2.06 , P = 0.03 ) ; similar findings were observed for breast development . In boys , HAZ and BMI Z at age 5 y were positively associated with pubic hair development ( RRR : 1.78 , P < 0.001 and RRR : 1.43 , P < 0.01 , respectively ) ; HAZ at age 5 y was associated with development of genitals ( RRR : 2.19 , P < 0.01 ) . Conclusion : In boys and girls , both height and body mass index in early childhood predicted the trajectory of pubertal development . This may provide a tool to identify children at risk of early pubertal onset OBJECTIVE The objective of this study was to determine the influence of  birth weight and postnatal weight gain  on age at menarche . DESIGN , SETTING , AND PARTICIPANTS This was a prospect i ve cohort study where girls from the West Australian Pregnancy ( Raine ) Cohort Study were followed prospect ively from fetal life ( 18 wk of pregnancy ) to adolescence ( 12 - 14 yr ) . MAIN OUTCOME MEASURE Age at menarche was the main outcome measure . RESULTS Growth status at birth was judged by expected birth weight ratio ( EBW ; a ratio of observed infant 's birth weight over median birth weight appropriate for maternal age , weight , height , parity , infant sex , and gestational age ) . Postnatal growth status was judged by body mass index ( BMI ) . Both EBW ( P = 0.020 ) and BMI in childhood ( 8 yr of age ) ( P < 0.001 ) were associated with age at menarche . Menarche occurred earlier in girls with lower EBW and higher BMI . CONCLUSIONS We have demonstrated for the first time that both birth weight and weight gain in childhood are associated with age at menarche . Weight gain before birth and subsequent weight gain up to the age of 8 yr were found to have opposing influences on the timing of menarche . Lower EBW combined with higher BMI during childhood predicted early age at menarche , and this relationship existed across normal birth weight and BMI ranges Aims /hypothesisEarlier age at menarche is associated with increased BMI and obesity risk from early childhood through to adulthood . We hypothesised that earlier age at menarche would also predict subsequent diabetes risk . Methods This was a population -based prospect i ve cohort study of 13,308 women , who were aged 40 to 75 years between 1993 and 1997 and participating in the Norfolk cohort of the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC-Norfolk ) . We used data on age at menarche and ascertained diabetes incidence to 2005 . Results There were 734 cases of diabetes ( 363 incident and 371 prevalent cases ) . Mean age at menarche was lower in women with diabetes than in non-diabetic women ( 12.8 vs 13.0 years , p = 0.008 ) . Compared with the earliest quintile ( menarche at 8–11 years ) , women in the oldest quintile ( menarche at 15–18 years ) had lower BMI ( 25.5 vs 27.4 kg/m2 , p < 0.0001 ) and a reduced risk of diabetes ( OR 0.66 [ 95 % CI 0.51–0.86 ] adjusted for age , family history , physical activity , smoking , occupational social class , parity and use of hormonal preparations ) . The association between age at menarche and diabetes was linear ( adjusted OR 0.91 [ 95 % CI 0.87–0.96 ] per 1 year later menarche ) and appeared to be completely mediated by adult BMI or waist circumference ( OR 0.98 [ 95 % CI 0.93–1.03 ] , further adjusted for BMI at age 40–75 years ) . Conclusions /interpretationEarlier age at menarche increases the risk of diabetes in women and this association appears to be mediated by increased adiposity . History of earlier menarche may help to identify women with increased subsequent risk of diabetes Background Lack of appropriate reporting of method ological details has previously been shown to distort risk of bias assessment s in r and omized controlled trials . The same might be true for observational studies . The goal of this study was to compare the Newcastle-Ottawa Scale ( NOS ) assessment for risk of bias between review ers and authors of cohort studies included in a published systematic review on risk factors for severe outcomes in patients infected with influenza . Methods Cohort studies included in the systematic review and published between 2008–2011 were included . The corresponding or first authors completed a survey covering all NOS items . Results were compared with the NOS assessment applied by review ers of the systematic review . Inter-rater reliability was calculated using kappa ( K ) statistics . Results Authors of 65/182 ( 36 % ) studies completed the survey . The overall NOS score was significantly higher ( p < 0.001 ) in the review ers ’ assessment ( median = 6 ; interquartile range [ IQR ] 6–6 ) compared with those by authors ( median = 5 , IQR 4–6 ) . Inter-rater reliability by item ranged from slight ( K = 0.15 , 95 % confidence interval [ CI ] = −0.19 , 0.48 ) to poor ( K = −0.06 , 95 % CI = −0.22 , 0.10 ) . Reliability for the overall score was poor ( K = −0.004 , 95 % CI = −0.11 , 0.11 ) . Conclusions Differences in assessment and low agreement between review ers and authors suggest the need to contact authors for information not published in studies when applying the NOS in systematic review CONTEXT Adult women with polycystic ovary syndrome ( PCOS ) have decreased GnRH pulse generator sensitivity to progesterone (P)-mediated slowing . This defect is and rogen mediated because it is reversed with and rogen receptor blockade . Adolescent hyper and rogenism often precedes PCOS . OBJECTIVE The aim of the study was to evaluate GnRH pulse generator sensitivity to P-mediated slowing in normal and hyper and rogenic girls . DESIGN We conducted a controlled interventional study . SETTING The study was conducted in a general clinical research center . PARTICIPANTS A total of 26 normal control ( NC ) and 26 hyper and rogenic ( HA ) girls were studied . INTERVENTION Frequent blood sampling was performed for 11 h to assess LH pulse frequency before and after 7 d of oral estradiol and P. MAIN OUTCOME MEASURE We measured the slope of the percentage reduction in LH pulse frequency as a function of d 7 P ( slope ) . RESULTS Overall , Tanner 3 - 5 HA subjects were less sensitive to P-mediated slowing than Tanner 3 - 5 NC ( slope , 4.7 + /- 3.4 vs. 10.3 + /- 7.7 ; P = 0.006 ) . However , there was variability in the responses of HA subjects ; 15 had P sensitivities within the range seen in NC , whereas nine were relatively P insensitive . The two groups had similar testosterone levels . Fasting insulin levels were higher in P-insensitive HA girls ( 39.6 + /- 30.6 vs. 22.2 + /- 13.9 microIU/ml ; P = 0.02 ) , and there was an inverse relationship between fasting insulin and P sensitivity in HA girls ( P = 0.02 ) . Tanner 1 - 2 NC had lower testosterone levels and were more P sensitive than Tanner 3 - 5 NC ( slope , 19.3 + /- 5.8 ; P = 0.04 ) . CONCLUSIONS Hyper and rogenism is variably associated with reduced GnRH pulse generator sensitivity to P-mediated slowing during adolescence . In addition to and rogen levels , insulin resistance may modulate P sensitivity CONTEXT Rapid postnatal weight gain has been associated with subsequent increased childhood adiposity . However , the contribution of rapid weight gain during specific infancy periods is not clear . OBJECTIVE We aim ed to determine which periods of infancy weight gain are related to childhood adiposity and also to age at menarche in UK girls . DESIGN , SETTING , AND PARTICIPANTS A total of 2715 girls from a prospect i ve UK birth cohort study participated in the study . MAIN OUTCOME MEASURES Routinely measured weights and lengths at ages 2 , 9 , and 19 months were extracted from the local child health computer data base . Body composition was assessed by dual-energy x-ray absorptiometry at age 10 yr , and age at menarche was assessed by question naire ( categorized into three groups : < 12.0 , 12.0 - 13.0 , and > 13.0 yr ) . RESULTS Faster early infancy weight gain between 0 and 2 months and also 2 to 9 months were associated with increased body fat mass relative to lean mass at age 10 yr and also with earlier age at menarche . Each + 1 unit gain in weight sd score between 0 and 9 months was associated with an odds ratio ( 95 % confidence interval ) = 1.48 ( 1.27 - 1.60 ) for overweight ( body mass index > 85th centile ) at 10 yr , and 1.34 ( 1.21 - 1.49 ) for menarche at less than 12 yr . In contrast , subsequent weight gain between 9 and 19 months was not associated with later adiposity or age at menarche . CONCLUSIONS In developed setting s , rapid weight gain during the first 9 months of life is a risk factor for both increased  childhood adiposity and early menarche in girls STUDY OBJECTIVE To analyze age at menarche and its association with excess weight and body fat percentage . DESIGN School-based cross-sectional survey . SETTING Southwestern region of the Brazilian Amazon . PARTICIPANTS The sample was made up of 727 girls , in the 8- to 16-year age range , divided into 3 groups : early , normal , and late menarche , from public and private schools , selected through proportional stratified r and om sampling . INTERVENTIONS AND MAIN OUTCOME MEASURES  Bioimpedance  was used to  measure body fat percentage and body mass index , applying the Global School-Based Student Health Survey question naire to categorize behavior variables . Age at menarche was determined using the status quo method . Sexual maturity was assessed through self- assessment according to criteria described by Tanner . RESULTS Overall age at menarche was 11. 
    Output:
    