Prospective Association Of Hair Cortisol Concentration As Biomarker Of Chronic Stress With Pubertal Secondary Sexual Characteristics Development

ObjectiveThe hypothesis of association between chronic stress with early puberty development in boys and girls"is tested in this study by using hair cortisol concentration（HCC）as a biomarker of chronic stress.MethodsParticipants were recruited directly in grades 1 through 3 from 2 large elementary schools of Bengbu,Anhui Province,China,in March 2016.According to the principle of informed consent,a child development and health queue was established.Hair samples from 1 263 children were obtained.A commercially available enzyme-linked immunosorbent assay kit for salivary cortisol was used to measure cortisol concentrations.At the same time,parental and children’s questionnaire was implemented to collect information on birth dates,physical activity,screen time,sleep duration,sugar-beverage consumption,weight status,as well as socio-economic status.Follow-up of adolescent secondary sexual development（boys’testicular volume,girl’s breast Tanner staging）until March 2017.1 069（518 boys and 551 girls）Children with HCC and adolescent development follow-up data were included in the study.The cortisol content was non-normally distributed and expressed as P₅₀(P₂₅^P₇₅).Mann-Whitney U test was used to compare gender differences.The Kruskal-Wallis test of k independent samples was used to compare HCC concentrations in children with different body weight status and different family economic conditions.According to testicular or breast development of boys and girls,puberty development is divided into developmental non-progression group,new development group and developmental progress group.The Kruskal-Wallis test was used to compare the differences in HCC between children with different stages of adolescent development.According to the"Chinese Age of Childhood Adolescent Growth Phase Assessment"prepared by the research group,we evaluated whether puberty development at the end of follow-up was advanced.HCC is divided into Q1^Q4 four groups（quartile Q1 as the reference group）according to the quartiles concentration,corrected for age,physical activity,video time,sleep time,sugar-sweetened beverage intake,weight status and family economy Condition,a multivariate Logistic regression model was used to analyze the correlation between different quartiles of cortisol distribution and early adolescent development at the end of follow-up.ResultsBaseline survey of 2 326 children,including qualified hair samples and successful detection of 1 263 children with cortisol concentrations,598 boys and 665 girls,with an average age of（8.0±0.8）years.One year later,1069 children were successfully followed up,with an average age of（9.0±0.8）years.Of these,518 were boys and 551were girls.The average BMI was（18.32±3.29）kg/m2.At the end of follow-up,the detection rates of the undeveloped breast development group,new development group,and developmental group were 55.9%（308）,30.1%（166）,and 14%（77）respectively;the testicular volume of boys was not developed.The detection rates of the progress,new development group and developmental progress group were 94.2%（488）,5.4%（28）,and 0.4%（2）respectively.The rate of early detection of breast development in girls was 23.2%（128 persons）,and the detection rate of testicular volume in boys was6.9%（36 persons）.The median cortisol concentration（HCC）[interquartile range]concentration was11.76[IQR:10.56,13.09]pg/mg.HCC in girls was significantly higher in the newly developed group（12.02[IQR:10.57,13.57]）and developmental progression group（12.47[IQR:11.26,13.49]）than in the undeveloped group（11.50[IQR:10.47,12.78]）.Statistical significance（χ²=15.51,P<0.001）.There was no statistical difference in HCC of boys in the undeveloped group（11.81[IQR:10.58,13.05]）,newly developed group（12.37[IQR:11.08,13.54]）and developmental progress group（13.11[IQR:12.51,13.11]）.Significance（χ²=2.68,P=0.262）.There was no significant difference in the development of testicular volume between the advanced and non-advanced age groups in boys with HCC（Z=1.056,P=0.291）;in the girls’early breast development(P₅₀=12.45)and non-advanced group(P₅₀=11.53)The difference was statistically significant（Z=3.049,P=0.002）.After age,physical activity,screen time,sleep duration,sugar-beverage consumption,weight status,as well as socio-economic status,compared with HCC in Q1 level,girls whose HCC in Q4 level had 1.87（1.20³.20）higher rates in early breast development.ConclusionThis study was based on a cohort of healthy children and used cortisol concentration as a biomarker of childhood chronic stress to objectively evaluate the developmental level of secondary sexual characteristics in boys and girls and to carry out a one-year follow-up.The results suggest that chronic stress and the risk of early breast development in girls closely related.This study expands the limitations of chronic stress assessment methods and cross-sectional surveys that rely on subjective reporting in previous related studies,and further supports the hypothesis that“social stress accelerates adolescent development in advance”proposed by the theory of social psychological acceleration.