Onset In Girls Research Articles

Urinary gonadotropin assay on 24-h collections as a tool to detect early central puberty onset in girls: determination of predictive thresholds.

Is the 24-h urinary gonadotropin assay an effective diagnostic tool in central precocious puberty (CPP) in girls? This study is the first to provide 24-h urinary gonadotropin assay data, using an electrochemiluminescent immunoassay (CMIA), and to report its usefulness as a tool for the diagnosis of CPP. Data about the GnRH test in the diagnosis of CPP are variable and there is no consensus regarding its interpretation. The measurement of FSH and LH in urines was previously reported to be an alternative biological tool. This is a retrospective two-cohort study, involving a setting and a validation cohort. A total of 516 girls, included between October 2012 and July 2015, and 632 urinary collections were analyzed in the setting cohort. In the validation cohort, 39 girls were included between January 2021 and May 2023, and 49 urinary collections were analyzed. This study included girls who consulted for an investigation of disturbed growth rate or a clinical suspicion of puberty onset in different medical centres across France (setting cohort). Girls with a suspicion of precocious puberty onset were addressed at the expert centre of paediatric endocrinology of the Groupement Hospitalier Lyon Est (validation cohort). Pelvic ultrasonography was performed and enabled their classification according to clinical and morphologic changes criteria (prepubertal or pubertal groups). The parents collected 24-h urine samples (u24) according to standardized instructions. FSH and LH (urinary or plasmatic) were measured using a current and automated CMIA. The area under the ROC curves for CPP prediction was 0.709 for u24FSH (P < 0.001), 0.767 for u24LH (P < 0.001), and 0.753 for the u24LH/u24FSH ratio (P < 0.001). We retained all possible combinations of the four thresholds in the validation cohort (u24FSH = 1.1 or 2.0 IU/24h; u24LH = 0.035 or 0.08 IU/24h). The combination of u24FSH > 1.1 IU/24h and u24LH > 0.08 IU/24h had a positive PV of 85.7% and a negative PV of 94.3%, a sensitivity of 85.7% and a specificity of 94.3%, for classifying prepubertal and pubertal girls in this cohort. This is a retrospective study, in which a margin of error remains due to the inherent uncertainty regarding the clinical assessment of pubertal onset. It must be considered that the thresholds can only apply to the used reagents; measurements without extractions using other reagents are likely to show important heterogeneity. The assay performed herein is a simple, non-invasive, and analytically robust technique meeting the criteria for an alternative to the GnRH test which could be used to supplement its lack of sensitivity. No specific funding was used. All authors declared no conflict of interest. In-house #23-5214 registered study.

Creatine Acts as a Mediator of the Causal Effect of Obesity on Puberty Onset in Girls: Evidence from Mediation Mendelian Randomization Study.

Epidemiological studies have linked obesity to the onset of puberty, while its causality and the potential metabolite mediators remain unclear. We employed a two-sample Mendelian randomization (MR) design to evaluate the causal effects of obesity on puberty onset and its associated diseases including type 2 diabetes (T2D) and cardiovascular diseases (CVDs). The potential mediators in this pathway were further explored using a two-step MR design. The robustness of our findings was evaluated using sensitivity analyses. Our MR results revealed that childhood obesity/BMI were causally associated with an increased Tanner stage in girls, younger age at menarche, and increased risk of adulthood T2D and CVD. However, neither childhood BMI nor obesity had a causal effect on the Tanner stage in boys. Mediation analysis further indicated that increased creatine served as a mediator for the causal pathway from childhood obesity/BMI to the Tanner stage of girls, while early puberty onset in girls played a mediating role in the pathway linking childhood obesity to increased risk of adulthood T2D and CVD. This study indicated that the risk of early puberty onset in girls and its associated health issues can be potentially reduced by preventing childhood obesity. The involvement of creatine in this process needs to be further validated and explored.

Time trends towards earlier puberty in boys and girls with type 1 diabetes: Insights from the German Diabetes Prospective Follow-up (DPV) registry, 2000 to 2021.

To examine the time trends and factors associated with the onset of puberty in children with type 1 diabetes (T1D) using data from the German Diabetes Prospective Follow-up (Diabetes-Patienten-Verlaufsdokumentation [DPV]) registry. A total of 13 127 children with T1D, aged 6 to 18 years, were included in the analysis. Regression analysis was performed to investigate the relationship between diabetes duration, body mass index (BMI) standard deviation score (SDS), glycated haemoglobin (HbA1c) level, migration background, and the onset of puberty, stratified by sex. Our findings revealed a significant trend towards earlier puberty in both girls and boys with T1D over the observed period (2000 to 2021). Puberty onset in girls (thelarche Tanner stage B2) decreased from 11.48 (11.35-11.65) years in 2000 to 10.93 (10.79-11.08) years in 2021 and gonadarche (Tanner stage G2/testicular volume >3 mL) decreased from 12.62 (12.42-12.82) years in 2000 to 11.98 (11.79-12.16) years in 2021 in boys (both P < 0.001). Longer diabetes duration, higher BMI SDS, and lower HbA1c level were associated with earlier puberty in both sexes (P < 0.001). Our study highlights earlier puberty in children with T1D, influenced by BMI SDS, HbA1c level, and migration background. This has important implications for diabetes management and supporting healthy development. Further research is needed to understand the underlying mechanisms and develop potential interventions for this vulnerable population.

Persistent high exposure to exogenous phthalates and endogenous sex hormones associated with early pubertal onset among children: A 3.5-year longitudinal cohort study in China

BackgroundEarly onset of puberty could have significant impacts on childhood health, but the extent to which it was affected by phthalate esters (PAEs) and sex hormone disruption was not understood. The aim of this study is to investigate the associations between exposure to PAEs and sex hormone disruption and early onset of puberty in children. MethodsA longitudinal cohort study was conducted in China from May 2017 to Oct 2020, involving 740 children during consecutive visits. The onset of puberty was evaluated using Tanner definition, and early puberty was defined as an onset age less than the first 25 %, with cut-offs of 10.33 and 8.97 years for boys and girls, respectively. Serum testosterone (TT), estradiol (E2) and urinary PAE metabolites were measured during three visits. Generalized linear models were used to explore the associations between PAE and sex hormones with the age of puberty onset, while log-binomial regressions were applied to assess the associations of persistent exposure to PAEs and sex hormones with early pubertal onset. ResultsApproximately 86.0 % of boys and 90.2 % of girls completed puberty onset from pre-puberty, and more than 95 % of participants had PAE concentrations higher than the limit of detection. Boys showed higher exposure to PAE pollutants and higher TT levels. Persistent exposure to PAEs was positively associated with early pubertal onset in girls (ARR = 1.97, 95 %CI = 1.12, 3.46). Moreover, persistent exposure to PAEs and E2 had synergistic associations with early pubertal onset in both boys (ARR = 4.77, 95 %CI = 1.06, 21.54) and girls (ARR = 7.07, 95 %CI = 1.51, 33.10). However, PAEs and TT had antagonistic associations only in boys (ARR = 0.44, 95 %CI = 0.07, 2.58). ConclusionLong-term exposure to PAEs might increase the risk of early pubertal onset, and it appears to work in synergy with E2, while in antagonism with TT in boys’ early pubertal onset. Reducing PAEs exposure might promote pubertal health.

Accuracy of doppler assessment of the uterine arteries for the diagnosis of pubertal onset in girls: a scoping review

The uterine artery pulsatility index (PI) assessed by Doppler ultrasound reflects the impedance to the blood flow in the vessel distal to the sampling point. We aimed to assess the accuracy of the uterine artery PI for the diagnosis of puberty in girls. A PRISMA-ScR-compliant scoping review was performed in the MEDLINE and Embase databases with the search terms “puberty” and “Doppler ultrasonography”. Studies that included girls aged 0–18 years who underwent pelvic Doppler ultrasound with calculation of uterine artery PI were eligible. Ten studies comprising 1385 girls aged 1.2–18 years were included. The selected studies included participants from Italy, Brazil, Iran, Belgium and Denmark, and were published between 1996 and 2021. Six studies selected girls who were referred for evaluation of pubertal disorders, while four studies included only healthy girls. Nine studies found a significant difference in Doppler signal pattern and PI according to pubertal stage, with PI cutoff points ranging from 2.5 to 4.6 for the diagnosis of puberty, with a sensitivity of 77%–94%, specificity of 85%–100%, and accuracy of 79%–98%. Doppler assessment of the uterine arteries with PI calculation is a useful noninvasive tool in the diagnosis of pubertal onset in girls.

Comparison of physician- and self-assessed pubertal onset in Japanese children.

Physical examinations to assess pubertal development are challenging in large epidemiological surveys. This study aimed to assess the reliability of judgment of pubertal onset in Japanese children by the original pubertal self-assessment sheet. A total of 144 children aged 10 or 12 years were recruited between March 2019 and September 2020 from the pediatric endocrine outpatient clinics of participating institutions. Agreement between the physician- and participantassessed pubertal onsets was determined using unweighted kappa (UK) and Gwet's agreement coefficient (AC1). The physician's assessment of pubertal onset was in slight agreement with that of the self-assessment sheet in 10-year-old boys (UK: 0.23 and AC1: 0.14), whereas the agreement between the physician's assessment and self-assessment sheet results was good and the physician's assessment was fair (UK: 0.64 and AC1: 0.94) in 12-year-old boys. The physician's assessment of pubertal onset were in good and moderate agreement with the self-assessment sheet in 10-year-old girls (UK/AC1: 0.74/0.78, respectively). In 12-year-old girls, although it showed poor agreement with UK (0.46), there was a very good agreement with AC1 (0.88). Although self-assessment of breast development was in good agreement with that of the physician's assessment for determining pubertal onset in girls, large-scale epidemiological studies are difficult to conduct for adolescent boys, especially for those in the early pubertal stage.

Neighborhood Racial and Economic Privilege and Timing of Pubertal Onset in Girls

PurposeEarly puberty is associated with adverse health outcomes over the life course, and Black and Hispanic girls experience puberty earlier than girls of other racial/ethnic backgrounds. Neighborhood racial and economic privilege may contribute to these disparities by conferring differential exposure to mechanisms (e.g., stress, obesity, endocrine disruptors) underlying early puberty. We examined associations between neighborhood privilege, measured by the Index of Concentration at the Extremes (ICE), and age at pubic hair onset (pubarche) and breast development onset (thelarche) in a large multiethnic cohort. MethodsA cohort of 46,299 girls born 2005–2011 at Kaiser Permanente Northern California medical facilities were followed until 2021. Pubertal development was assessed routinely by pediatricians using the Sexual Maturity Rating scale. ICE quintiles for race/ethnicity, income, and income + race/ethnicity were calculated using American Community Survey 2010 5-year estimates and linked to census tract at birth. We fit multilevel Weibull regression models accommodating left, right, and interval censoring for all analyses. ResultsICE measures were monotonically associated with pubertal onset, with the strongest associations observed for ICE–race/ethnicity. Adjusting for maternal education, age at delivery, and parity, girls from the least versus most privileged ICE–race/ethnicity quintiles were at increased risk for earlier pubarche (hazard ratio: 1.30, 95% confidence interval: 1.21, 1.38) and thelarche (hazard ratio: 1.45, 95% confidence interval: 1.36, 1.54). These associations remained significant after adjusting for girls' race/ethnicity and childhood body mass index. Additionally, adjustment for ICE partially attenuated Black–White and Hispanic–White disparities in pubertal onset. DiscussionNeighborhood privilege may contribute to pubertal timing and related disparities.

Exposure to a mixture of personal care product and plasticizing chemicals in relation to reproductive hormones and menarche timing among 12-19 years old girls in NHANES 2013-2016.

The effects of co-exposure to personal care product and plasticizing chemicals (PCPPCs) on reproductive hormones and menarche timing has rarely been studied. We used Bayesian kernel machine regression (BKMR), adaptive least absolute shrinkage and selection operator (adaptive LASSO), and generalized linear model (GLM) to explore the mixture effects of 16 PCPPCs on reproductive hormones and early menarche among 297 girls aged 12-19 years in the National Health and Nutrition Examination Survey (NHANES) 2013-2016. In the BKMR, the mixture of PCPPCs was negatively and positively associated with testosterone (TT) and sex hormone-binding globulin (SHBG), respectively. In the adaptive LASSO, 2,5-dichlorophenol (2, 5-DCP), Mono (carboxyisoctyl) phthalate (MCOP), and Mono-benzyl phthalate (MBzP) were positively associated with estrogen (E2), whereas Mono-ethyl phthalate (MEP), Monoisobutyl phthalate (MiBP) and Mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) were inversely associated with E2. Bisphenol A (BPA) and MBzP were positively associated with SHBG, whereas Mono (carboxyisonony) phthalate (MCNP) and Mono (2-ethyl-5-carboxypentyl) phthalate (MECPP) were inversely associated with SHBG. In GLM, Benzophenone-3 (BZP) and MECPP were negatively associated with TT, whereas 2,4-dichlorophenol (2,4-DCP) revealed a positive association with early menarche onset. In conclusion, PCPPCs in the mixture and individually are associated with reproductive hormones and early menarche onset in girls.

ODP376 Accuracy of Doppler Assessment of the Uterine Arteries for the Diagnosis of Pubertal Onset in Girls: A Scoping Review

Abstract Introduction The uterine artery pulsatility index (PI) assessed by Doppler ultrasonography (US) reflects the blood flow impedance in the vessel distal to the sampling point and tends to decrease with the onset of puberty, being suggested as a parameter to define pubertal development. Objective To evaluate the accuracy of the uterine artery PI for the diagnosis of puberty in girls. Methods A PRISMA-ScR-compliant scoping review was performed in the MEDLINE and Embase databases with "puberty" and "Doppler ultrasonography" as search terms. Studies that included girls aged 0-18 years who underwent pelvic US with Doppler of the uterine arteries and calculation of the PI were considered eligible. Results Ten studies comprising 1385 girls aged 1.2-18 years were included. The selected studies were published between 1996 and 2021 and included participants from five countries (Italy, Brazil, Iran, Belgium and Denmark). Six studies included girls who were referred for evaluation of pubertal disorders, mainly thelarche or early-onset pubarche, while four studies selected only healthy girls. Nine studies found a significant difference in Doppler and PI according to pubertal stage, with PI cutoff points ranging from 2.5 to 4.6 for the diagnosis of onset of puberty, with a sensitivity of 77-94%, specificity of 85-100% and accuracy of 79-98%. Conclusion Doppler assessment of the uterine arteries with PI calculation is a useful noninvasive tool in the diagnosis of onset of secondary sexual characteristics in girls. Presentation: No date and time listed

ISPAD Clinical Practice Consensus Guidelines 2022: Diabetes in adolescence.

ISPAD Clinical Practice Consensus Guidelines 2022: Diabetes in adolescence.

Polycyclic aromatic hydrocarbons are associated with later puberty in girls: A longitudinal study

The objective of this study is to explore associations between PAH exposures and puberty timing in girls. Beginning in May 2014, 734 girls age 7.2–11.8 years in Chongqing, China, were enrolled in a prospective cohort study. They were followed up every 6 months from enrollment through June 2021, at which point participants were ages 13.6–18.3 years. Metabolite concentrations of four PAHs (1-hydroxypyrene [1-OHPyr], 2-hydroxynaphthalene [2-OHNap], 2-hydroxyfluorine [2-OHFlu], and 9-hydroxyphenanthrene [9-OHPhe]) were measured in urine samples at baseline. At each follow up visit, the Tanner's Sexual Maturity Rating scale was administered. Cox proportional hazards models were used to estimate associations between four urinary PAH metabolite concentrations and four markers of puberty: menarche, breast development, pubic hair development, and axillary hair development. Geometric mean concentrations of 1-OHPyr, 2-OHNap, 2-OHFlu and 9-OHPhe in urine were 0.47 μg/L, 3.31 μg/L, 1.49 μg/L, 3.75 μg/L, respectively. There were statistically significant associations between several urinary PAH metabolite concentrations and puberty outcomes. PAH metabolite concentrations were grouped as Low (<25th percentile, referent group), Moderate (25th–75th percentile) or High (>75th). Girls with moderate levels of 1-OHPyr were at higher risk of delayed pubic hair development (hazard ratio [HR]: 0.82, 95 % confidence interval [CI]: 0.68–0.99). Delayed breast development (HR: 0.77, 95 % CI: 0.60–0.99) and pubic hair development (HR: 0.76, 95 % CI: 0.60–0.95) were associated with high 2-OHNap. High c 2-OHFlu was associated with delayed pubic hair development (HR: 0.77, 95 % CI: 0.61–0.96). Delayed breast (HR: 0.79, 95 % CI: 0.64–0.97), pubic hair (HR: 0.79, 95 % CI: 0.65–0.96) and axillary hair development (HR: 0.80, 95 % CI: 0.65–0.99) was associated with moderate 9-OHPhe. In conclusion, PAH exposure may delay puberty onset in girls.

Adiposity Status, Trajectories, and Earlier Puberty Onset: Results From a Longitudinal Cohort Study.

Adiposity is associated with earlier puberty onset in girls, but such an association among boys is controversial. To estimate the association of prepubertal adiposity status, trajectories, and the earlier puberty onset based on a cohort study. A total of 1322 children were included in 2017 (mean age of 8.1 ± 0.6 years for girls and 9.1 ± 0.6 years for boys) and were followed every 6 months until October 2020. Anthropometric profiles, including BMI, WC, and body composition indicators, were used to determine adiposity status. Group-based trajectory modeling was used to identify trajectory groups of anthropometric profiles. Testicular volume for boys and breast stage for girls were clinically assessed. Pubertal development was assessed through clinical inspection and palpation by using The Tanner rating map and Prader orchidometer. Covariate information was obtained through questionnaires. Childhood adiposity was associated with increased risk of earlier puberty onset. Body composition was more sensitive to earlier puberty onset than BMI and WC. Boys and girls with high-level body fat percentage had increased risk of earlier puberty onset compared with those with low-level body fat percentage. However, boys and girls with high-level FFM (fat-free mass)/FM (fat mass) had a decreased risk of earlier puberty onset compared with those with low-level FFM/FM. High-level trajectories of rapid increase in anthropometric profiles, in addition to FFM/FM, were also significantly associated with higher risk of earlier puberty onset. Prepubertal adiposity and distinct trajectories were associated with earlier puberty onset. It is important to maintain healthy adiposity status to prevent earlier puberty onset in children.

Prenatal and postnatal exposures to endocrine disrupting chemicals and timing of pubertal onset in girls and boys: a systematic review and meta-analysis.

Globally, the ages at pubertal onset for girls and boys have been decreasing during recent decades, partly attributed to excess body fat accumulation. However, a growing body of literature has recognized that endocrine disrupting chemicals (EDCs) may play an important role in this global trend, but the association has not yet been fully established. EDCs can interfere with normal hormone function and metabolism and play a role in pubertal onset. We aimed to systematically identify and evaluate the current evidence on the timing of pubertal onset in girls and boys following prenatal or postnatal exposures to xenobiotic EDCs. Following PRISMA guidelines, we performed a systematic literature search of original peer-reviewed publications in the PubMed database through a block search approach using a combination of index MeSH and free text search terms. Publications were considered if they covered biomarkers of prenatal or postnatal exposures to xenobiotic EDCs (European Commission's list of category 1 EDCs) measured in maternal or child biospecimen and pubertal onset defined by the progression of the following milestones (and assessed in terms of the following measures): menarche (age), thelarche (Tanner staging) and pubarche (Tanner staging), in girls, and genital stage (Tanner staging), testicular volume (ml) and pubarche (Tanner staging), in boys. The literature search resulted in 703 references, of which we identified 52 publications fulfilling the eligibility criteria for the qualitative trend synthesis and 23 publications for the meta-analysis. The qualitative trend synthesis provided data on 103 combinations of associations between prenatal or postnatal exposure to EDC compounds groups and puberty outcomes and the meta-analysis enabled 18 summary risk estimates of meta-associations. Statistically significant associations in the qualitative trend synthesis suggested that postnatal exposure to phthalates may be associated with earlier thelarche and later pubarche. However, we did not find consistent evidence in the meta-analysis for associations between timing of pubertal onset in girls and boys and exposures to any of the studied xenobiotic EDCs. We were not able to identify specific pre- or postnatal windows of exposure as particularly critical and susceptible for effects of EDCs. Current evidence is subject to several methodological challenges and inconsistencies and evidence on specific exposure-outcome associations remains too scarce to firmly confirm EDC exposure as a risk factor for changes in age of pubertal onset in the general child population. To create a more uniform foundation for future comparison of evidence and to strengthen pooled studies, we recommend the use of more standardized approaches in the choice of statistical analyses, with exposure transformations, and in the definitions and assessments of puberty outcomes. The impact of mixtures of EDC exposures on the association also remains unestablished and would be valuable to elucidate for prenatal and postnatal windows of exposure. Future large, longitudinal epidemiological studies are needed to clarify the overall association.

Accuracy of Doppler assessment of the uterine arteries in healthy girls for the diagnosis of pubertal onset.

To evaluate the accuracy of the uterine artery pulsatility index (PI) for the diagnosis of pubertal onset in girls. Cross-sectional study of girls with normal pubertal development. Puberty was diagnosed by the presence of Tanner breast development score ≥2. All girls underwent pelvic ultrasound and Doppler imaging of the uterine arteries. We evaluated the uterine artery PI and uterine, endometrial, and ovarian measurements. We used ROC curves with cutoffs determined by Youden index for data analysis. We included 169 girls aged 5-16 years who underwent 202 pelvic ultrasound examinations. Prepubertal girls had a significantly higher mean PI (6.70 ± 2.15) than girls in initial puberty (4.14 ± 1.55) and in late puberty (2.81 ± 1.05) (P < 0.001 for all comparisons), which reflects a progressive increase in blood flow to the uterus with the progression of puberty. ROC curve analysis showed that the PI was able to identify the onset of puberty with a mean area under the curve of 0.838 ± 0.04 (P < 0.001), and the PI cutoff point of 5.05 had a sensitivity of 77%, specificity of 85%, positive predictive value (PPV) of 92%, and accuracy of 79%. The combination of PI < 5.05 plus uterine volume >3.75 cm³ had a sensitivity of 73%, specificity of 95%, PPV of 97%, and accuracy of 79% to detect initial puberty. We found a significant reduction in the PI during pubertal development, which can possibly be a valuable noninvasive tool in the evaluation of pubertal disorders, alone or in combination with uterine and ovarian volumes.

Disorders of Puberty in Girls

Puberty is the process through which reproductive competence is achieved and comprises gonadarche and adrenarche. Breast development is the initial physical finding of pubertal onset in girls and typically occurs between 8 and 13 years. Menarche normally occurs 2 to 3 years after the onset of breast development. Pubertal onset is controlled by the gonadotropin-releasing hormone pulse generator in the hypothalamus; however, environmental factors such as alterations in energy balance and exposure to endocrine-disrupting chemicals can alter the timing of pubertal onset. Improvement in nutritional and socioeconomic conditions over the past two centuries has been associated with a secular trend in earlier pubertal onset. Precocious puberty is defined as onset of breast development prior to 8 years and can be central or peripheral. Delayed puberty can be hypogonadotropic or hypergonadotropic and is defined as lack of breast development by 13 years or lack of menarche by 16 years. Both precocious and delayed puberty may have negative effects on self-esteem, potentially leading to psychosocial stress. Patients who present with pubertal differences require a comprehensive assessment to determine the underlying etiology and to devise an effective treatment plan.

Endocrine-Disrupting Chemicals and Early Puberty in Girls.

In recent decades, pubertal onset in girls has been considered to occur at an earlier age than previously. Exposure to endocrine-disrupting chemicals (EDCs) has been associated with alterations in pubertal timing, with several reports suggesting that EDCs may have a role in the secular trend in pubertal maturation, at least in girls. However, relevant studies give inconsistent results. On the other hand, the majority of girls with idiopathic precocious or early puberty present the growth pattern of constitutional advancement of growth (CAG), i.e., growth acceleration soon after birth. Herein, we show that the growth pattern of CAG is unrelated to exposure to endocrine-disrupting chemicals and is the major determinant of precocious or early puberty. Presented data suggest that EDCs, at most, have a minor effect on the timing of pubertal onset in girls.

Association of Infant Physical Development and Rapid Growth With Pubertal Onset Among Girls in Rural China

Whether physical development and rapid growth during the first 2 years of life are associated with puberty onset in girls remains unclear. To examine the associations of infant physical development and rapid growth with the timing of puberty onset in girls. This prospective birth cohort study included girls whose mothers had participated in a randomized, double-blind cluster trial of micronutrient supplementation with a daily capsule of folic acid, iron and folic acid, or multiple micronutrients during pregnancy. A total of 547 singleton girls in rural western China who were born after 2004 were followed up at 3, 6, 12, and 24 months of age and were eligible for long-term follow-up. Of these, 294 adolescent girls (aged 10-12 years), representing 53.7% of the total sample, were included in the follow-up interview that was conducted from June 1 through December 31, 2016. Data analyses were conducted from November 1, 2019, to May 30, 2020. Infant weight and length were assessed at birth and 3, 6, 12, and 24 months of age. Rapid growth, defined as a weight-for-age or length-for-age z score increase of greater than 0.67, was calculated during 5 periods: birth to 3 months, birth to 6 months, 6 to 12 months, 12 to 24 months, and birth to 24 months of age. Puberty stage was assessed using the standardized Tanner staging system. Onset of puberty was defined as attaining Tanner stage 2 of breast development or pubic hair growth, and the corresponding age at follow-up was recorded. Of 294 girls included in the analysis (mean [SD] age, 11.25 [0.57] years), the median age of puberty onset was 11 (interquartile range, 10-11) years. A significant association with puberty onset was found for infancy weight-for-age z score at 12 months of age (adjusted hazard ratio [HR], 1.20; 95% CI, 1.01-1.44) and rapid weight gain from birth to 24 months of age (adjusted HR, 1.40; 95% CI, 1.01-1.93) and birth to 3 months of age (adjusted HR, 1.39; 95% CI, 1.02-1.91). However, length-related indicators during early life were not associated with adolescent puberty onset. This study found that a higher weight-for-age z score and rapid weight gain during infancy, particularly from birth to 3 months of age, were associated with an increased likelihood of puberty onset in girls. These findings suggest that weight-related indicators may serve as proxies of puberty onset among adolescent girls.

Doppler Assessment of the Uterine Arteries for the Definition of Pubertal Onset in Girls

Abstract Pelvic ultrasonography (US) is a quick, non-invasive and low-cost method, and doppler analysis facilitates assessment of flow impedance measurement in the uterine vascular tree. The pulsatility index (PI) reflects blood flow impedance in the vessel distal to the sampling point and has been suggested as a parameter to define pubertal development. In order to evaluate the PI and US measurements of uterus and ovaries in girls with different pubertal stages, we performed a cross-sectional study in girls with normal pubertal development. US and Doppler assessed PI of the uterine arteries (defined as the difference between the peak systolic flow and end-diastolic flow divided by the mean maximum flow velocity), endometrial thickness, uterine and ovarian volumes were evaluated. All the US exams were performed with the same equipment by the same radiologist. Clinical data such as the age of menarche, pubarche and thelarche were recorded. Statistical analyses were performed in SPSS, with ANOVA test, Spearman correlation and ROC curve with Youden. One hundred and sixty-nine girls aged 5-16 years (mean 11.3 ± 1.8) who performed two hundred and two pelvic US were included (Tanner 1=20%, Tanner 2=22%, Tanner 3=23%, Tanner 4=17%, Tanner 5=17%). Mean age of thelarche, pubarche and menarche were 11.1 ± 1.8, 10.2 ± 1.2 and 12.2 ± 1.1 years respectively. Prepubertal girls (Tanner 1) had mean PI significantly higher than girls in initial puberty (Tanner 2 and 3 grouped) and in late puberty (Tanner 4 and 5 grouped), respectively 6.5 ± 2.27 vs. 4.15 ± 1.55 vs. 2.82 ± 1.06, p&amp;lt;0.001 for all the comparisons. ROC curve analysis demonstrated that the PI is able to identify the onset of puberty with an area under the curve of 0.80 ± 0.04, P&amp;lt;0.001, and a cutoff point of IP=5.05 presented a sensitivity of 0.77 and a specificity of 0.80 to identify the onset of puberty. When we combined the cutoffs of IP &amp;lt;5.05 plus uterine volume &amp;gt;3.75 cm³, we found a sensitivity of 0.72 and specificity of 0.90 to detect puberty. We identified a strong negative correlation between PI and uterine volume (rs=-0.72, p&amp;lt;0.001) and a moderate negative correlation with endometrial thickness (rs=-0.68, p&amp;lt;0.001) and right (rs=-0.60, p&amp;lt;0.001) and left (rs=-0.59, p&amp;lt;0.001) ovarian volumes. In conclusion, we found a significant reduction of the PI during pubertal development, reflecting a progressive increase in blood flow to the uterus, which can be a valuable non-invasive and highly specific tool to confirm the onset of puberty.

Timing of Pubertal Onset in Girls and Boys With Constitutional Delay.

The decision whether to treat a child with delayed puberty with sex steroids is primarily based on patient, family, and provider preference. Knowing when children with constitutional delay eventually enter puberty would inform this decision. To estimate and compare rates of pubertal entry, we conducted a retrospective cohort study by reviewing medical records of children evaluated for delayed puberty at a large academic medical center between 2000 and 2015, extracting data on pubertal status for all clinical visits, then conducting time-to-event analyses. Of 392 girls and 683 boys with delayed puberty, constitutional delay was the most common cause, found in 32% of girls and 70% of boys. In a subcohort of 97 girls and 243 boys who were prepubertal at one or more visits, we observed a broad age range for pubertal entry, up to >16 years for girls and >17 years for boys. The probability of entering puberty within the next year for 12- to 15.5-year-old girls and 13.5- to 16.5-year-old boys with delayed puberty ranged between 38% and 74%. No differences in the rates of pubertal entry were seen between girls and boys after data harmonization. The broad range of ages at pubertal entry for children with constitutional delay challenges the concept that constitutional delay is merely an extreme of normal variation. Discussions with patients and families about management should consider the possibility that some children may need to wait years after presentation until puberty starts.

Exposure to non-persistent pesticides and puberty timing: a systematic review of the epidemiological evidence

Numerous modern non-persistent pesticides have demonstrated estrogenic/anti-androgenic activity and have been classified as endocrine-disrupting chemicals (EDCs). Processes involved in puberty development are vulnerable to EDCs, such as compounds that interfere with the metabolism or activity of sex steroids. To conduct a systematic review of epidemiological studies on the relationship between early-life exposure to non-persistent pesticides and puberty timing and/or sexual maturation in girls and boys. A systematic search was carried out using MEDLINE and SCOPUS databases, including original articles published up to November 2020. Thirteen studies were selected after excluding non-original and non-human studies. Exposure to different types of pesticides has been associated with altered puberty timing in girls and/or boys in eight studies. In utero exposure to atrazine has been related to earlier age of menarche in girls; exposure to organophosphate (OP) pesticides has been related to delayed sexual development in boys and girls; childhood pyrethroid exposure has been associated with pubertal delay in girls and pubertal advancement in boys; and prenatal/childhood exposure to multiple pesticides has been linked to earlier puberty onset in girls and pubertal delay in boys. Most of the reviewed studies describe a relationship between pesticide exposure and changes in the age of puberty onset or sex hormone levels, although the quality of the evidence is generally low. Further well-designed longitudinal studies are warranted on specific classes of pesticides and on possible interactions between different types of compounds.