Timing of puberty in boys and girls: A population-based study.
ABSTRACT: BACKGROUND:A secular trend towards earlier puberty has been observed in girls, while a similar trend has been more uncertain in boys. We estimated current ages at pubertal development in both boys and girls. METHODS:In this population-based cohort study, 14 759 of 22 439 invited boys and girls born from 2000 to 2003 in the Danish National Birth Cohort gave half-yearly self-reported information on puberty from the age of 11.5 years and throughout puberty. This late start of follow-up limits the estimation of age at onset of puberty but not later pubertal milestones. We estimated mean age at attaining the following pubertal milestones in years with 95% confidence intervals (CI): age at menarche, voice break, first ejaculation of semen and Tanner stages for pubic hair development and breast development or genital development. Further, the difference in mean age at menarche between mothers and daughters was estimated. RESULTS:In boys, voice break occurred at 13.1 (95% CI 13.0, 13.1) years, first ejaculation of semen occurred at 13.4 (95% CI 13.3, 13.4) years, and Tanner Genital Stage 5 occurred at 15.6 (95% CI 15.5, 15.6) years. In girls, age at menarche occurred at 13.0 (95% CI 13.0, 13.1) years and Tanner Breast Stage 5 occurred at 15.8 (95% CI 15.7, 15.9) years. Daughters had menarche 3.6 (95% CI 3.1, 4.2) months earlier than their mothers had. CONCLUSION:These data indicate that age at menarche has declined and to some extent support a decline in age at attaining other markers of pubertal development among boys.
Project description:Because early puberty has been linked to diseases later in life, identification of modifiable causes of early puberty is of interest. We explored the possible associations between maternal smoking during pregnancy and pubertal development in sons and daughters. Between 2012 and 2017, 15,819 children from the Danish National Birth Cohort, born during 2000-2003, provided half-yearly information on puberty from the age of 11 years. We estimated adjusted age differences (in months) at attaining various pubertal milestones, including Tanner stages, per 10 daily cigarettes smoked in the first trimester of gestation. In sons, exposure to smoking in utero was associated with earlier genital development (Tanner 2, -1.3 months, 95% confidence interval (CI): -2.5, 0.0; Tanner 5, -3.7 months, 95% CI: -5.3, -2.0), pubic hair development (Tanner 2, -1.8 months, 95% CI: -2.9, -0.6; Tanner 5, -2.9 months, 95% CI: -4.2, -1.7), and voice break (-2.4 months, 95% CI: -3.6, -1.3). In daughters, maternal smoking was associated with earlier breast development (Tanner 2, -3.4 months, 95% CI: -5.3, -1.5; Tanner 5, -4.7 months, 95% CI: -6.5, -2.9), pubic hair development stages 3-5 (Tanner 5, -2.5 months, 95% CI: -4.1, -1.0), and menarche (-3.1 months, 95% CI: -4.0, -2.3). Fetal exposure to tobacco smoke might advance timing of puberty in boys and girls.
Project description:BACKGROUND:Polybrominated diphenyl ether (PBDE) flame retardants are endocrine-disrupting chemicals that exhibit estrogenic and androgenic properties and may affect pubertal timing. METHODS:Study subjects were participants between 1999 and 2013 in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a longitudinal cohort study of predominantly Mexican origin families in Northern California. We measured serum concentrations of four PBDEs (BDE-47, -99, -100, -153) in blood collected from mothers during pregnancy (N=263) and their children at age 9years (N=522). We determined timing of pubertal onset in 309 boys and 314 girls using clinical Tanner staging every 9months between 9 and 13years of age, and timing of menarche by self-report. We used Poisson regression for relative risk (RR) of earlier puberty and parametric survival analysis for time ratios (TR) of pubertal milestones. RESULTS:Prenatal concentrations of all 4 congeners and ?PBDEs were associated with later menarche in girls (RRearlier menarche=0.5, 95% confidence interval (CI): 0.3, 0.9 for ?PBDEs) but earlier pubic hair development in boys (RRearlier pubarche=2.0, 95% CI: 1.3, 3.3 for ?PBDEs). No associations were seen between prenatal exposure and girls' breast or pubic hair development or boys' genital development. Childhood PBDE exposure was not associated with any measure of pubertal timing, except for an association of BDE-153 with later menarche. CONCLUSIONS:We found that prenatal PBDE exposure was associated with later menarche in girls but earlier pubarche in boys, suggesting opposite pubertal effects in girls and boys.
Project description:BACKGROUND:It remains unsettled whether prenatal exposure to perfluoroalkyl substances (PFASs) affects human reproductive health through potential endocrine disruption. OBJECTIVES:We aimed to explore the associations between prenatal exposure to several PFASs and various aspects of pubertal development in boys and girls. METHODS:We studied two samples ([Formula: see text] and 445) from the Puberty Cohort, nested within the Danish National Birth Cohort (DNBC), measuring PFAS in maternal plasma from early gestation. Data on pubertal development were collected biannually from the age of 11 y until full maturation, using web-based questionnaires. Outcomes were age at menarche, voice break, first ejaculation, and Tanner stages 2 to 5 for pubic hair, breast, genital development, and a combined puberty indicator. A regression model for censored data was used to estimate mean difference (months) in age at achieving the pubertal outcomes across tertiles of PFAS concentrations and with a doubling of PFAS concentrations (continuous). For perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), a meta-analysis was used to provide a weighted average of the point estimates from samples 1 and 2. RESULTS:Overall, prenatal exposure to PFOS, perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PDFA) (girls) and PFHxS and PFHpS (boys) was associated with lower mean age at puberty marker onset. PFDA and PFNA exposure was associated with higher mean age at onset of puberty in boys. Nonmonotonic associations in girls (PFOS, PFHpS, PFDA) and boys (PFDA, PFNA) were observed, showing larger mean age differences for the combined puberty indicator in the middle tertile [girls: PFOS: [Formula: see text] mo, 95% confidence interval (CI): [Formula: see text], [Formula: see text]; PFHpS: [Formula: see text] mo, 95% CI: [Formula: see text], 1.85; PFDA: [Formula: see text] mo, 95% CI: [Formula: see text], 1.83; and boys: PFNA: 4.45 mo, 95% CI: [Formula: see text], 10.21; PFDA: 4.59 mo, 95% CI: [Formula: see text], 10.11] than in the highest tertile with the lowest as reference. CONCLUSIONS:Our population-based cohort study suggests sex-specific associations of altered pubertal development with prenatal exposure to PFASs. These findings are novel, and replication is needed. https://doi.org/10.1289/EHP3567.
Project description:BACKGROUND:Earlier pubertal timing has been observed in many countries. We aimed to explore if prenatal exposure to maternal obesity, smoking, and alcohol intake was associated with timing of puberty by use of a novel marker of pubertal timing: 'the height difference in standard deviations' (HD:SDS). METHODS:HD:SDS is the difference between pubertal height in standard deviations and adult height in standard deviations, and it correlates well with age at peak height velocity. Pubertal height was measured by health care professionals at approximately 13 years in boys and 11 years in girls, and the children's adult height was predicted from parental height reported by the mothers during pregnancy. Information on HD:SDS was available for 42,849 of 56,641 eligible boys and girls from the Danish National Birth Cohort born 2000-2003. In a subsample, HD:SDS was validated against age at the following self-reported pubertal milestones: Tanner stages, menarche, first ejaculation, voice break, acne, and axillary hair. Prenatal exposures were reported by mothers during pregnancy. RESULTS:HD:SDS correlated moderately with the pubertal milestones considered (correlation coefficients: - 0.20 to - 0.53). With normal weight (body mass index (BMI): 18.5-24.9 kg/m2) as the reference, maternal pre-pregnancy obesity (BMI: 30.0+ kg/m2) was associated with earlier pubertal timing: 0.23 (95% confidence interval (CI): 0.18, 0.28) higher HD:SDS in boys and 0.19 (95% CI, 0.14, 0.24) higher HD:SDS in girls. Maternal smoking was not associated with pubertal timing. Compared to alcohol abstainers, maternal intake of > 3 units of alcohol weekly was associated with later puberty in boys only: 0.14 (95% CI, 0.05, 0.24) lower HD:SDS. CONCLUSION:As correlations between HD:SDS and the considered pubertal milestones were comparable to those reported in the literature between age a peak height velocity and the considered pubertal milestones, the validity of HD:SDS seems acceptable. Maternal pre-pregnancy obesity was associated with earlier pubertal timing in both sexes, and maternal alcohol intake during pregnancy was associated with later pubertal timing in boys. Maternal smoking has been linked to earlier timing of puberty, but this was not replicated in our setting using HD:SDS as a marker of pubertal timing.
Project description:<h4>Background</h4>The factors influencing pubertal timing have gained much attention due to a secular trend toward earlier pubertal onset in many countries. However, no studies have investigated the association between the Great earthquake and early puberty. We aimed to assess whether the Wenchuan earthquake is associated with early puberty, in both boys and girls.<h4>Methods</h4>We used data from two circles of a survey on reproductive health in China to explore the impact of the Wenchuan earthquake on early puberty , and a total of 9,785 adolescents (4,830 boys, 49.36%) aged 12-20 years from 29 schools in eight provinces were recruited. Wenchuan earthquake exposure was defined as those Sichuan students who had not experienced oigarche/menarche before May 12, 2008. Early puberty was identified as a reported onset of oigarche/menarche at 11 years or earlier. We tested the association between the Wenchuan earthquake and early puberty in boys and girls. Then, subgroup analysis stratified by the age at earthquake exposure also was performed.<h4>Results</h4>In total, 8,883 adolescents (4,543 boys, 51.14%) with a mean (SD) age of 15.13 (1.81) were included in the final sample. In general, children exposed to the earthquake had three times greater risk of early puberty (boys, RR [95% CI] = 3.18 [2.21-4.57]; girls: RR [95%CI] =3.16 [2.65-3.78]). Subgroup analysis showed that the adjusted RR was 1.90 [1.19-3.03] for boys and 2.22 [1.75-2.80] for girls. Earthquake exposure predicted almost a fourfold (RR [95%CI] = 3.91 [1.31-11.72]) increased risk of early puberty in preschool girls, whereas the increase was about twofold (RR [95%CI] = 2.09 [1.65-2.64]) in schoolgirls. Among boys, only older age at earthquake exposure was linked to early puberty (RR [95%CI] = 1.93 [1.18-3.16]).<h4>Conclusions</h4>Wenchuan earthquake exposure increased the risk of early puberty in boys and girls, and preschoolers were more at risk than schoolchildren. The implications are relevant to support policies for those survivors, especially children, to better rebuild after disasters.
Project description:BACKGROUND:Systemic inflammation may play a role in shaping breast composition, one of the strongest risk factors for breast cancer. Pubertal development presents a critical window of breast tissue susceptibility to exogenous and endogenous factors, including pro-inflammatory markers. However, little is known about the role of systemic inflammation on adolescent breast composition and pubertal development among girls. METHODS:We investigated associations between circulating levels of inflammatory markers (e.g., interleukin-6 (IL-6), tumor necrosis factor receptor 2 (TNFR2), and C-reactive protein (CRP)) at Tanner stages 2 and 4 and breast composition at Tanner stage 4 in a cohort of 397 adolescent girls in Santiago, Chile (Growth and Obesity Cohort Study, 2006-2018). Multivariable linear models were used to examine the association between breast composition and each inflammatory marker, stratifying by Tanner stage at inflammatory marker measurement. Accelerated failure time models were used to evaluate the association between inflammatory markers concentrations at each Tanner stage and time to menarche. RESULTS:In age-adjusted linear regression models, a doubling of TNFR2 at Tanner 2 was associated with a 26% (95% CI 7-48%) increase in total breast volume at Tanner 4 and a 22% (95% CI 10-32%) decrease of fibroglandular volume at Tanner 4. In multivariable models further adjusted for body fatness and other covariates, these associations were attenuated to the null. The time to menarche was 3% (95% CI 1-5%) shorter among those in the highest quartile of IL-6 at Tanner 2 relative to those in the lowest quartile in fully adjusted models. Compared to those in the lowest quartile of CRP at Tanner 4, those in the highest quartile experienced 2% (95% CI 0-3%) longer time to menarche in multivariable models. CONCLUSIONS:Systemic inflammation during puberty was not associated with breast volume or breast density at the conclusion of breast development among pubertal girls after adjusting for body fatness; however, these circulating inflammation biomarkers, specifically CRP and IL-6, may affect the timing of menarche onset.
Project description:OBJECTIVES:To estimate age at attaining Tanner stages in Ugandan/Zimbabwean HIV-infected children initiating antiretroviral therapy (ART) in older childhood and investigate predictors of delayed puberty, particularly age at ART initiation. DESIGN:Observational analysis within a randomized trial. METHODS:Tanner staging was assessed every 24 weeks from 10 years of age, menarche every 12 weeks and height every 4-6 weeks. Age at attaining different Tanner stages was estimated using normal interval regression, considering predictors using multivariable regression. Growth was estimated using multilevel models with child-specific intercepts and trajectories. RESULTS:Median age at ART initiation was 9.4 years (inter-quartile range 7.8, 11.3) (n?=?582). At the first assessment, the majority (80.2%) were in Tanner stage 1; median follow-up with staging was 2.8 years. There was a strong delaying effect of older age at ART initiation on age at attaining all Tanner stages (P?<?0.05) and menarche (P?=?0.02); in boys the delaying effect generally weakened with older age. There were additional significant delays associated with greater impairments in pre-ART height-for-age Z-score (P?<?0.05) in both sexes and pre-ART BMI-for-age in girls (P?<?0.05). There was no evidence that pre-ART immuno-suppression independently delayed puberty or menarche. However, older children/adolescents had significant growth spurts in intermediate Tanner stages, and were still significantly increasing their height when in Tanner stage 5 (P?<?0.01). CONCLUSION:Delaying ART initiation until older childhood substantially delays pubertal development and menarche, independently of immuno-suppression. This highlights that factors other than CD4, such as pubertal development, need consideration when making decisions about timing of ART initiation in older children.
Project description:The COPENHAGEN Puberty Study is a combined cross sectional and longitudinal population based cohort study of healthy Danish children and adolescents. The clinical evaluations were performed by trained physicians and included pubertal staging of breast development according to Tanner´s classification evaluated by palpation. As a measure of pubertal onset a testicular volume of 4 ml or a breast tanner stage of B2 or more was used for boys and girls, respectively. The mean age between two examinations where this threshold was reached was used as their age of pubertal onset. Pre- and post-pubertal samples from 20 girls and 31 boys, in total 102 samples, were normalised using a Subset quantile Within-Array Normalization (SWAN) procedure and probes containing SNPs in the CpG or extension sites were removed.
Project description:The aim of this study was to examine the relative contributions of body mass index (BMI) and pubertal measures for risk and age of onset of pediatric MS.Case-control study of 254 (63% female) MS cases (onset<18 years of age) and 420 (49% female) controls conducted at 14 U.S. Pediatric MS Centers. Sex- and age-stratified BMI percentiles were calculated using CDC growth charts from height and weight measured at enrollment for controls, and within 1 year of onset for MS cases. Sex-stratified associations between MS risk and age at symptom onset with both BMI and pubertal factors were estimated controlling for race and ethnicity.Only 11% of girls and 15% of boys were prepubertal (Tanner stage I) at MS onset. 80% of girls had onset of MS after menarche. BMI percentiles were higher in MS cases versus controls (girls: P < 0.001; boys: P = 0.018). BMI was associated with odds of MS in multivariate models in postpubertal girls (OR = 1.60, 95% confidence interval [CI]: 1.12, 2.27, P = 0.009) and boys (OR = 1.43, 95% CI: 1.08, 1.88, P = 0.011). In girls with MS onset after menarche, higher BMI was associated with younger age at first symptoms (P = 0.031). Younger menarche was associated with stronger effects of BMI through mediation and interaction analysis. In pubertal/postpubertal boys, 89% of whom were obese/overweight, earlier sexual maturity was associated with earlier onset of MS (P < 0.001).Higher BMI in early adolescence is a risk factor for MS in girls and boys. Earlier age at sexual maturity contributes to earlier age at MS onset, particularly in association with obesity.
Project description:Early pubertal timing has been associated with adult diseases, and identifying preventable causes is of importance. In utero exposure to exogenous glucocorticoids, has been associated with changes in the reproductive hormonal axes in the children, which may influence pubertal timing. Exogenous glucocorticoids can be indicated for diseases such as asthma, allergy, skin diseases, as well as muscle and joint diseases. The aim was to explore the association between in utero exposure to glucocorticoids and pubertal timing in the children. This population-based study was conducted in the Puberty Cohort including 15,819 children, which is a sub-cohort of the Danish National Birth Cohort. Information on maternal glucocorticoid treatment was collected through interviews during pregnancy. Information on pubertal timing was obtained by questionnaires every 6 months throughout puberty, including Tanner Stages, axillary hair, acne, voice break, first ejaculation and menarche. The potential impact of confounding by indication was explored by stratifying on indication and treatment status. Overall, 6.8% of the children were exposed to glucocorticoids in utero. Exposure to glucocorticoids in utero was not associated with earlier puberty for neither boys nor girls with combined estimates of 0.4 months (95% CI: -1.5; 2.2) and -0.7 months (95% CI: -2.5; 1.2).