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Objective: To demonstrate sexual dimorphism in serum leptin levels not only during puberty, but also in childhood in Japan. Design: Cross-sectional study. Setting: Hamamatsu-Hokuen study in Japan. Subjects: Body weight and height were measured in normal-weight Japanese children and adolescents (143 boys, 178 girls), and 161 boys and 129 girls whose percentage of overweight for the standard (%Wt) was more than+25%. Serum leptin levels were compared with %Wt. Subjects were divided into group 1 (6–10 y of age) and group 2 (11–15 y of age) according to their age. Results: In overweight subjects, leptin was more highly correlated with %Wt in boys of group 2 (r=0.67, P

Polycyclic aromatic hydrocarbons (PAHs) are endocrine-disrupting chemicals. Few studies have evaluated the association between pubertal development in girls and PAH exposures quantified by urinary biomarkers.We examined associations of urinary PAH metabolites with pubertal development in 358 girls 6-16 years of age from the San Francisco Bay Area enrolled in a prospective cohort from 2011 to 2013 and followed until 2020. Using baseline data, we assessed associations of urinary PAH metabolites with pubertal development stage. In prospective analyses limited to girls who at baseline had not yet started breast (N = 176) or pubic hair (N = 179) development or menstruation (N = 267), we used multivariable Cox proportional hazards regression to assess associations of urinary PAH metabolites with the onset of breast and pubic hair development, menstruation, and pubertal tempo (interval between the onset of breast development and menstruation).We detected PAH metabolites in98% of girls. In cross-sectional analyses using baseline data, PAH metabolites were not associated with the pubertal development stage. In prospective analyses, higher concentrations (≥ median) of some PAH metabolites were associated with two-fold higher odds of earlier breast development (2-hydroxy naphthalene, 1-hydroxy phenanthrene, summed hydroxy phenanthrenes) or pubic hair development (1-hydroxy naphthalene) among girls overweight at baseline (body mass index-for-age percentile ≥85) compared with nonoverweight girls with lower metabolites concentrations. PAH metabolites were not associated with age at menarche or pubertal tempo.PAH exposures were widespread in our sample. Our results support the hypothesis that, in overweight girls, PAHs impact the timing of pubertal development, an important risk factor for breast cancer.

Previous empirical research on pubertal development among Black boys is limited. The present study examined the ethnic-racial composition of neighborhoods as a moderator in the relation between pubertal indicators and depressive symptoms among a nationally representative sample of African American and Caribbean Black boys.The present study utilized the male sample (The results indicate that Black boys with early developing hair growth who lived in neighborhoods with higher percentages of Black residents had higher depressive symptoms compared to their early developing counterparts in neighborhoods with fewer Black residents. African American males with early developing hair growth had higher depressive symptoms compared to Caribbean Black males with early developing hair growth regardless of neighborhood context.Early pubertal timing is a risk for African American boys' mental health regardless of neighborhood context. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

In brief Sex differences in the gut microbiome may impact multiple aspects of human health and disease. In this study, we review the evidence for microbial sex differences in puberty and adulthood and discuss potential mechanisms driving differentiation of the sex-specific gut microbiome. Abstract In humans, the gut microbiome is strongly implicated in numerous sex-specific physiological processes and diseases. Given this, it is important to understand how sex differentiation of the gut microbiome occurs and how these differences contribute to host health and disease. While it is commonly believed that the gut microbiome stabilizes after 3 years of age, our review of the literature found considerable evidence that the gut microbiome continues to mature during and after puberty in a sex-dependent manner. We also review the intriguing, though sparse, literature on potential mechanisms by which host sex may influence the gut microbiome, and vice versa, via sex steroids, bile acids, and the immune system. We conclude that the evidence for the existence of a sex-specific gut microbiome is strong but that there is a dearth of research on how host–microbe interactions lead to this differentiation. Finally, we discuss the types of future studies needed to understand the processes driving the maturation of sex-specific microbial communities and the interplay between gut microbiota, host sex, and human health.

[Abstract] Derry Girls (2018–present), Channel 4’s major success since Max and Paddy’s Road to Nowhere (2004), is a teen sitcom set in pre-ceasefire Northern Ireland, which inevitably brings issues such as place and space to the fore by relying on teen drama tropes. This is particularly visible in “The Concert”, Derry Girls’ third episode in season two, directed by Michael Lennox and written by Lisa McGee, an episode where the dominant tropes are those of a road movie but genuinely overturned upside down. Such a subversion will be directly connected to notions of space, identity and containment during the Troubles in the 1990s, as well as youth, gender, ethnicity and class divides. [Resumen] Derry Girls (2018–presente), el mayor éxito de Channel 4 desde Max y Paddy’s Road to Nowhere (2004), es una comedia de situación para adolescentes ambientada en Irlanda del Norte antes del alto el fuego que, como no podría ser de otra manera, aborda cuestiones como el espacio a través de tropos habituales en la audiovisual adolescente. Esto es particularmente apreciable en “El concierto”, el tercer episodio de su segunda temporada, dirigido por Michael Lennox y escrito por Lisa McGee, un episodio donde los tropos dominantes son los del género de la road movie pero invertidos. Tal subversión estará directamente relacionada con cuestiones como espacio, identidad y contención durante el Conflicto norirlandés en la década de los noventa, así como con los confines de la adolescencia, el género, la etnia o clase social.

Objective: The current study aimed to determine the onset of sesamoid bones (Sbs) ossification at the thumb metacarpophalangeal (MCP) joint of the hand and its relationship with puberty. Methods: This retrospective radiographic study included patients aged 5-17 years. The presence of Sbs was investigated separately for each age group. Patients were classified based on their age, gender, and the presence of radial and ulnar sesamoids. Results: A total of 1,020 radiographs from 939 patients were analyzed. Sbs began to ossify in girls at the age of 8 years and in boys at the age of 9 years. The ulnar-radial sesamoids were present in all individuals in the same age group at the age of 13-14 years in girls and 15 years in boys. The age at which 50% of the individuals in the same age group had a sesamoid was 10.4 years in girls and 11.9 years in boys on the radial side, 9.5 years in girls, and 11.5 years in boys on the ulnar side. Conclusions: In all individuals, the time between the onset of sesamoids of the MCP joint and development corresponds to the physiological period of puberty. However, the age at which puberty begins coincides with the time when Sbs begin to ossify in 50% of both sexes in the same age group Amaç: Bu çalışma, elin başparmak metakarpofalangeal (MKP) ekleminde sesamoid kemiklerin (Sbs) kemikleşme zamanının başlangıcını ve ergenlik dönemi ile ilişkisini belirlemeyi amaçlamıştır. Yöntemler: Bu retrospektif radyografik çalışmaya 5-17 yaş arası hastalar dahil edildi. Her yaş grubu için ayrı ayrı Sbs varlığı araştırıldı. Hastalar yaş, cinsiyet ve radyal-ulnar sesamoid varlığına göre kaydedildi. Bulgular: Dokuz yüz otuz dokuz hastanın 1.020 radyografisi incelendi. Sbs kızlarda 8, erkeklerde 9 yaşında kemikleşmeye başladı. Aynı yaş grubundaki tüm bireylerde ulnar-radyal sesamoidlerin bulunduğu yaş kızlarda 13-14, erkeklerde 15 idi. Sesamoidin aynı yaş grubundaki bireylerin %50’sinde görüldüğü yaş radyal taraf için kızlarda 10,4, erkeklerde 11,9 iken ulnar taraf için ise kızlarda 9,5, erkeklerde 11,5 yaş olarak belirlendi. Sonuçlar: Örneklemimizde ergenlik başlangıç zamanı ve süresi ile karşılaştırıldığında; 1. MKP eklemdeki sesamoidlerin görülmeye başladığı yaştan tüm bireylerde görülmeye başladığı yaşa kadar geçen süre fizyolojik ergenlik süresi ile benzerdir. Ergenlik başlangıç yaşı ise aynı yaş grubundaki hem cinslerinin %50’sinde Sbs’nin görüldüğü zamana denk gelmektedir

Background: In the Netherlands, treatment with puberty suppression is available to transgender adolescents younger than age 18 years. When gender dysphoria persists testosterone or oestradiol can be added as gender-affirming hormones in young people who go on to transition. We investigated the proportion of people who continued gender-affirming hormone treatment at follow-up after having started puberty suppression and gender-affirming hormone treatment in adolescence. Methods: In this cohort study, we used data from the Amsterdam Cohort of Gender dysphoria (ACOG), which included people who visited the gender identity clinic of the Amsterdam UMC, location Vrije Universiteit Medisch Centrum, Netherlands, for gender dysphoria. People with disorders of sex development were not included in the ACOG. We included people who started medical treatment in adolescence with a gonadotropin-releasing hormone agonist (GnRHa) to suppress puberty before the age of 18 years and used GnRHa for a minimum duration of 3 months before addition of gender-affirming hormones. We linked this data to a nationwide prescription registry supplied by Statistics Netherlands (Centraal Bureau voor de Statistiek) to check for a prescription for gender-affirming hormones at follow-up. The main outcome of this study was a prescription for gender-affirming hormones at the end of data collection (Dec 31, 2018). Data were analysed using Cox regression to identify possible determinants associated with a higher risk of stopping gender-affirming hormone treatment. Findings: 720 people were included, of whom 220 (31%) were assigned male at birth and 500 (69%) were assigned female at birth. At the start of GnRHa treatment, the median age was 14·1 (IQR 13·0–16·3) years for people assigned male at birth and 16·0 (14·1–16·9) years for people assigned female at birth. Median age at end of data collection was 20·2 (17·9–24·8) years for people assigned male at birth and 19·2 (17·8–22·0) years for those assigned female at birth. 704 (98%) people who had started gender-affirming medical treatment in adolescence continued to use gender-affirming hormones at follow-up. Age at first visit, year of first visit, age and puberty stage at start of GnRHa treatment, age at start of gender-affirming hormone treatment, year of start of gender-affirming hormone treatment, and gonadectomy were not associated with discontinuing gender-affirming hormones. Interpretation: Most participants who started gender-affirming hormones in adolescence continued this treatment into adulthood. The continuation of treatment is reassuring considering the worries that people who started treatment in adolescence might discontinue gender-affirming treatment. Funding: None.

Background Resource trade-off theory suggests that increased performance on a given trait comes at the cost of decreased performance on other traits. Methods Growth data from 1889 subjects (996 girls) were used from the GrowUp1974 Gothenburg study. Energy Trade-Off (ETO) between height and weight for individuals with extreme body types was characterized using a novel ETO-Score (ETOS). Four extreme body types were defined based on height and ETOI at early adulthood: tall-slender, short-stout, short-slender, and tall-stout; their growth trajectories assessed from ages 0.5-17.5 years.A GWAS using UK BioBank data was conducted to identify gene variants associated with height, BMI, and for the first time with ETOS. Results Height and ETOS trajectories show a two-hit pattern with profound changes during early infancy and at puberty for tall-slender and short-stout body types. Several loci (including FTO, ADCY3, GDF5, ) and pathways were identified by GWAS as being highly associated with ETOS. The most strongly associated pathways were related to “extracellular matrix,” “signal transduction,” “chromatin organization,” and “energy metabolism.” Conclusions ETOS represents a novel anthropometric trait with utility in describing body types. We discovered the multiple genomic loci and pathways probably involved in energy trade-off.

Isoflavones are phytoestrogens with recognized estrogenic activity but may also affect testosterone, corticosterone and thyroid hormone levels in experimental models. However, the molecular mechanisms involved in these alterations are still unclear. Isoflavones are present in soy-based infant formula, in breast milk after the consumption of soy by the mother and are widely used for the preparation of beverages consumed by toddlers and teenagers. In this sense, we proposed to investigate the effects of soy isoflavone exposure during the prepubertal period, a recognized window of sensitivity for endocrine disruption, over the hypothalamic-pituitary-testicular (HPT) axis. For this, 42 3-week-old male Wistar rats were exposed to 0.5, 5 or 50 mg of soy isoflavones/kg from postnatal day (PND) 23 to PND60. We evaluated body growth, age at puberty, serum concentrations of LH, FSH, testosterone and estradiol, and the expression of the transcripts (mRNA) of genes encoding key genes controlling the hypothalamic-pituitary-testicular (HPT) axis. In the hypothalamus, we observed an increase in Esr1 mRNA expression (0.5 and 5 mg). In the pituitary, we observed an increase in Gnrhr mRNA expression (50 mg), a reduction in Lhb mRNA expression (0.5 mg), and a reduction in Ar mRNA expression. In the testis, we observed an increase in Lhcgr mRNA expression (50 mg) and a reduction in Star mRNA expression (0.5 and 5 mg). The serum levels of LH (5 and 50 mg) and FSH (0.5 mg) were increased, while testosterone and estradiol were reduced. Puberty was delayed in all groups. Taken together, these results suggest that prepubertal consumption of relevant levels of soy isoflavones disrupts the HPT axis, causing hypergonadotropic hypogonadism and altered expression levels of key genes regulating the axis.

Children with intracranial germ cell tumors may present premature sexual development via either gonadotrophin-releasing hormone (GnRH)-dependent cause or GnRH-independent cause. We conducted a single-center retrospective study on 37 precocious puberty (PP) patients with intracranial germ cell tumors and 25 age-matched prepubertal patients with elevated human chorionic gonadotropin (hCG) levels. Classification of PP was derived from hCG, gonadotropin and sex steroid levels and their changes. Five boys were assigned to GnRH-dependent group (G1). Thirty-one boys and one girl were assigned to GnRH-independent group (G2) with a median hCG of 76.75 (8.29–2747) IU/L. Seven boys and 18 girls were conducted as controls, with a median hCG of 17.12 (2.91–1062) IU/L. Patients in G1 had constant pubertal LH and testosterone levels after tumor complete response. Patients in G2 had hCG levels that decreased simultaneously with testosterone/estradiol levels, prior to tumor regression. The differences in hCG levels and the gender ratio were significant between G2 and controls (P = 0.006 and P 0.001, separately). Among intracranial germ cell tumor patients with positive hCG, boys with significantly higher hCG levels more easily developed PP. Our results suggest that GnRH-independent PP commonly regresses together with tumor regression. In comparison, results were inconclusive in tying tumor regression to the regression of GnRH-dependent PP.

International audience; The aim of the current study was to evaluate the effects of different levels of weightlifting training on bone mineral density (BMD) at different body sites (whole body (WB), lumbar spine (LS), femoral neck (FN), upper limbs (UL) and lower limbs (LL)) in a group of adolescents. Three groups of pubertal boys aged 13-15 years were recruited, including a control group (which included 13 untrained adolescents), a moderately trained group (which included 13 non-elite weightlifters, with four sessions of 2 hours per week) and a highly trained group (which included 13 elite weightlifters, with eight sessions of 2 hours per week). The three groups were paired for age and maturation index (using Tanner stages). Body composition, bone mineral content (BMC) and BMD were evaluated by dual-energy X ray absorptiometry (DXA). Physical performance variables (including weightlifting specific exercises, counter movement jump and squat jump) were measured using validated methods. Results showed that the values of BMD and physical performance variables were greater in the group of elite weightlifters compared to the group of non-elite weightlifters and the control group. In addition, the values of BMD and physical performance variables were higher in the group of the non-elite weightlifters compared to those of the control group. After adjusting for lean mass and squat jump, lumbar spine BMD, FN BMD, UL BMD and LL BMD remained significantly higher in the elite weightlifters’ group compared to the two other groups. In conclusion, the current study suggests that elite adolescent weightlifters have greater bone health parameters compared to moderately-trained adolescent weightlifters and untrained adolescents.

Objectives Although at least 598 genes are involved in the development of the hypothalamo–pituitary–testicular (HPT) axis, mutations in only 75 genes have so far been shown to cause delayed puberty. Methods Six male patients with failed puberty, manifested as absence of pubertal changes by 18 years of age, underwent whole exome sequencing of genomic DNA with subsequent bioinformatics analysis and confirmation of selected variants by Sanger sequencing. Genes having plausibly pathogenic non-synonymous variants were characterized as group A (previously reported to cause delayed puberty), group B (expressed in the HPT-axis but no mutations therein were reported to cause delayed puberty) or group C (not reported previously to be connected with HPT-axis). Results We identified variants in genes involved in GnRH neuron differentiation (2 in group A, 1 in group C), GnRH neuron migration (2 each in groups A and C), development of GnRH neural connections with supra-hypothalamic and hypothalamic neurons (2 each in groups A and C), neuron homeostasis (1 in group C), molecules regulating GnRH neuron activity (2 each in groups B and C), receptors/proteins expressed on GnRH neurons (1 in group B), signaling molecules (3 in group C), GnRH synthesis (1 in group B), gonadotropins production and release (1 each in groups A, B, and C) and action of the steroid hormone (1 in group A). Conclusions Non-synonymous variants were identified in 16 genes of the HPT-axis, which comprised 4 in group A that contains genes previously reported to cause delayed puberty, 4 in group B that are expressed along HPT-axis but no mutations therein were reported previously to cause delayed puberty and 8 in group C that contains novel candidate genes, suggesting wider genetic causes of failed male puberty.

We sought to determine if penile growth at puberty causes new complications after childhood hypospadias repair.Consecutive Tanner 2-5 patients presenting with complications after childhood hypospadias repair were queried to determine if those problems occurred before, during or after puberty.There was a total of 82 patients, 15 Tanner 2-4, evaluated at a mean age of 28 years (range 12-66). These underwent an average of 3 (range 1-20) childhood operations, mostly using skin flaps. Two-thirds had nondistal hypospadias. The most common complication was dehiscence in 73%, with ventral curvature in 39%, neourethral strictures or meatal stenoses in 29% and fistulas in 15%. Many patients had more than 1 problem. Of these complications 80% were reported to have occurred before puberty, including all dehiscences and recurrent ventral curvature, while 15% were diagnosed in men at an average age of 47 years who developed neourethral strictures or meatal stenosis. Only 5% of complications were reported to have occurred during puberty.There is a bimodal presentation of complications after childhood hypospadias repair. Most occur before puberty, while a smaller number of obstructive lesions develop in middle age. We found few new complications occurring during penile growth at puberty. These data potentially impact discussions regarding optimal duration of followup after childhood hypospadias repair, and also can reassure caregivers considering repair in boys that the risk for new complications developing during puberty appears to be small.

This cross-sectional study assesses the prevalence of disordered eating in children and its associations with sex, pubertal maturation, and weight.

Sotos syndrome is characterized by overgrowth, distinctive facial appearance, and learning disability. It is caused by heterozygous mutations, including deletions of NSD1 located at chromosome 5q35. While advanced bone age can occur in some cases, precocious puberty (PP) is reported only in three cases until now. Here, we reported a case of Sotos syndrome diagnosed at the infancy period with central precocious puberty. The discovery of potential factors that trigger puberty is one of the central mysteries of pubertal biology. Depot gonadotropin-releasing hormone (GnRH) analogs constitute the first-line therapy in central precocious puberty (CPP), which has proven to be both effective and safe. In our cases, leuprolide acetate in maximum dose could not be successful for the control of pubertal progression, and cyproterone acetate (CPA) was added to therapy. Then, pubertal progression was controlled. In some specific syndromes with precocious puberty, such as Sotos syndrome, treatment can be challenging. Cyproterone acetate would be an asset for the benefit of treatment.

Earlier puberty has been associated with numerous adverse mental, emotional, and physical health outcomes. Obesity is a known risk factor for earlier puberty in girls, but research with boys has yielded inconsistent findings. We examined sex- and race/ethnicity-specific associations between childhood obesity and puberty in a multiethnic cohort of 129,824 adolescents born at a Kaiser Permanente Northern California medical facility between 2003 and 2011. We used Weibull regression models to explore associations between childhood obesity and breast development onset (thelarche) in girls, testicular enlargement onset (gonadarche) in boys, and pubic hair development onset (pubarche) in both sexes, adjusting for important confounders. Clear dose-response relationships were observed. Boys with severe obesity had the greatest risk for earlier gonadarche (hazard ratio = 1.23, 95% confidence limit: 1.15, 1.32) and pubarche (hazard ratio = 1.44, 95% confidence limit: 1.34, 1.55), while underweight boys had delayed puberty compared with peers with normal body mass index. A similar dose-response relationship was observed in girls. There were significant interactions between childhood body mass index and race/ethnicity. Childhood obesity is associated with earlier puberty in both boys and girls, and the magnitude of the associations may vary by race/ethnicity. Prevention of childhood obesity may delay pubertal timing and mitigate health risks associated with both conditions.

Objectives Prolactin (PRL) stimulates the mammary glands development; however, it also inhibits gonadotropin-releasing hormone (GnRH) secretion. We evaluated the relationship between PRL levels and puberty in girls with precocious breast development. Methods This study included 244 girls with breast development < 8 years of age. Patients were categorized as central precocious puberty (CPP) [peak luteinizing hormone (LH) levels ≥ 5 IU/L after GnRH stimulation] versus non-CPP (NPP) group. High PRL was defined as serum PRL > 17.9 ng/mL. Results High PRL was more common in NPP than in CPP group (17.6 vs. 8.1%, p=0.025), although mean PRL levels did not differ. In NPP group, the high PRL group had lower peak LH/follicle-stimulating hormone (FSH) ratio, and later LH peak time after GnRH stimulation than normal PRL group (all p Conclusions Girls with NPP showed higher proportion of high PRL than CPP group. High PRL group showed more features of prepubertal response in NPP group, and associated with decreased odds for CPP, suggesting the possibility of PRL role on breast development while suppressing hypothalamic–pituitary–gonadal axis activation in NPP girls.

Mini-puberty is defined as the period in infancy with elevated FSH and LH resulting in increased levels of sex hormones. It differs between boys and girls and its impact on future fertility is not completely known. This mini-review focus on the effects of mini-puberty on genital development and some aspects possibly related to future fertility.

Context Hypogonadism in Prader-Willi syndrome (PWS) is generally attributed to hypothalamic dysfunction or to primary gonadal defect. MKRN3, a maternal imprinted gene located on 15q11.2-q13 region, encodes makorin ring finger protein 3, whose deficiency causes precocious puberty, an extremely rare symptom in PWS. Objective This study aimed to evaluate MKRN3 levels in patients with PWS and to analyze its correlation with sexual hormone levels, insulin resistance and Body Mass Index (BMI). Methods We performed an observational cross-sectional study and enrolled 80 patients with genetically confirmed diagnosis of PWS with median age of 9.6 years. Results MKRN3 levels were measurable in 49 PWS patients with a geometric mean of 34.9 +/- 22 pg/ml (median: 28.4). Unmeasurable levels of MKRN3 were found in 31 patients. No statistically significant differences were found between patients with and without measurable MKRN3 levels for any clinical, biochemical, or genetic characteristics. However, MKRN3 levels were inversely correlated with HOMA-IR index (p: 0.005) and HbA1c (p: 0.046) values. No statistically significant correlations were found between MKRN3 and LH, estradiol and testosterone concentrations, pubertal development and genetic defect, whereas a direct correlation with FSH was found (p: 0.007). Conclusions The typical genetic defect of PWS should lead to unmeasurable levels of the MKRN3 protein due to the inactivation of the paternal allele. Measurable circulating MKRN3 could suggest the possible involvement of tissue-specific imprinting mechanisms and other regulatory factors in gene expression. Correlations with HOMA-IR index, HbA1c, and FSH suggest peripheral actions of MKRN3, but future studies are warranted to investigate this topic.

Pubertal timing is a robust predictor of externalizing and internalizing problems in adolescence, but controversies remain whether only early or off-time (both early and late) pubertal timing is associated with negative developmental outcomes and whether effects differ across perceptions of pubertal timing and actual biological pubertal timing. Additionally, less is known about the longevity of pubertal timing effects and mediators of effects that persist through adolescence and into adulthood. This longitudinal study investigated the effects of early and off-time pubertal timing, in form of perceived pubertal timing relative to peers and reported biological pubertal timing relative to age, on delinquency and depressive symptoms in adolescence and young adulthood between 2003 and 2022. Peer deviance and school connectedness were examined as mediators of any persisting effects. The sample included 704 youth (52% male, 76% African American, 22% Non-Hispanic White) who were assessed at four time points from early adolescence (Mean ages: 11.8, 13.2) to late adolescence (Mean age: 17.6) and young adulthood (Mean age: 27.7). Perceived off-time pubertal timing in males and early biological pubertal timing in both males and females were risk factors for persistent delinquency into young adulthood, but neither form of pubertal timing was associated with depressive symptoms. None of the effects were mediated by peer deviance or school connectedness. These findings advance the understanding of more nuanced effects of pubertal timing on adjustment problems in diverse youth as they develop from early adolescence to adulthood.

The adolescent brain undergoes tremendous structural and functional changes throughout puberty. Previous research has demonstrated that pubertal hormones can modulate sexually dimorphic changes in cortical development, as well as age-related maturation of the neural activity underlying cognitive processes. However, the precise impact of pubertal hormones on these functional changes in the developing human brain remains poorly understood. In the current study, we quantified the neural oscillatory activity serving visuospatial processing using magnetoencephalography, and utilized measures of dehydroepiandrosterone (DHEA) as an index of development during the transition from childhood to adolescence (i.e., puberty). Within a sample of typically developing youth (ages 9-15), a novel association between pubertal DHEA and theta oscillatory activity indicated that less mature children exhibited stronger neural responses in higher-order prefrontal cortices during the visuospatial task. Theta coherence between bilateral prefrontal regions also increased with increasing DHEA, such that network-level theta activity became more distributed with more maturity. Additionally, significant DHEA-by-sex interactions in the gamma range were centered on cortical regions relevant for attention processing. These findings suggest that pubertal DHEA may modulate the development of neural oscillatory activity serving visuospatial processing and attention functions during the pubertal period.

Purpose The objective of this study was to analyze vitamin D status and PTH concentrations in 6- to 8-year-old girls with central precocious puberty. Methods A cross-sectional clinical and blood testing study (calcium, phosphorus, 25(OH)D and PTH) was carried out in 78 girls with central precocious puberty (CPP group), aged 6.1–7.9 years. A control group was recruited (137 prepubertal girls, aged 6.1–8.2 years). The criteria of the US Endocrine Society were used for the definition of hypovitaminosis D. Results There were no significant differences in vitamin D status between both groups. There were no significant differences in 25(OH)D concentrations between CPP (25.4 ± 8.6 ng/mL) and control groups (28.2 ± 7.4 ng/mL). In contrast, PHT concentrations in CPP group (44.8 ± 16.3 pg/mL) were higher (p p Conclusion Vitamin D status in 6- to 8-year-old girls with CPP is similar to that in prepubertal girls. PTH concentrations were significantly higher in girls with CPP, and this could be considered as a physiological characteristic of puberty and, in this case, of pubertal precocity.

Noonan syndrome (NS) is a relatively common developmental disorder characterised by the association of craniofacial abnormalities, congenital heart defects, short stature and skeletal abnormalities, variable developmental delay/learning disability, and predisposition to certain cancers. NS is caused by germline mutations in genes encoding components or regulators of the RAS/mitogen-activated protein kinase (MAPK) signaling pathway. Although abnormalities in the hypothalamic-pituitary-gonadal axis have long been reported in NS patients, there is only scarce published data on this subject. Puberty is usually delayed of about two years for both boys and girls with NS. However, in the majority of patients, it starts spontaneously suggesting a normal hypothalamic - pituitary input. The lower fat mass usually observed in NS patients may influence the timing of puberty. Although there is almost no reliable data on this issue, it is usually considered that fertility is not affected in NS females. In contrast, primary testicular insufficiency, predominant on Sertoli cell function, is reported in NS males. However, the exact frequency of infertility in adult males is unknown. More generally, although the features of NS are well described during childhood, little is known about the progression of the disease in adulthood. Prospective long-term follow-up studies are required to further investigate gonadal function and fertility in NS adults and to clarify the long-term follow-up of these patients.

Congenital hypogonadotropic hypogonadism (CHH) is a group of rare diseases characterized by inadequate secretion of the gonadotropins LH (luteinizing hormone) and FSH (follicle stimulating hormone) during the physiological activation periods of the gonadotropic axis. The disease? (anomaly) is present from fetal life and usually persists throughout life. Clinically, hypogonadotropic hypogonadism is associated with neonatal clinical signs (micropenis, cryptorchidism in boys in about half of the cases). The diagnosis is sometimes only evoked in the presence of an absence or arrest of pubertal maturation in the adolescent, which is often poorly tolerated physically and psychologically. Different therapeutic options for pubertal induction have been described, but we lack the necessary larger randomized trials to define the best approaches for both sexes. Historically, congenital hypogonadotropic hypogonadism diagnosed at puberty is treated with testosterone injections. These injections allow the development of secondary sexual characteristics, without an increase in testicular volume in severe forms (FSH deficiency), and a pubertal statural peak. During the last twenty years, studies have underlined the beneficial role of recombinant gonadotropins to induce puberty in this population for future fertility. This is what we will develop.

Introduction Recombinant human growth hormone (rhGH) therapy effectively increases height in various disorders of childhood growth. However, whether rhGH affects pubertal timing is unclear. We aimed to review systematically published evidence on the effect of rhGH on pubertal timing. Methods Embase, Medline, and Cochrane library databases were searched until December 2021 on randomized and non-randomized controlled studies of rhGH in children. Results Twenty-five articles (n=1,438 children) were identified describing 12 randomized and 13 non-randomized controlled studies in children with idiopathic short stature (ISS; 15 studies), small for gestational age (n=6 studies), chronic renal failure (n=3), Noonan syndrome (n=1), and growth hormone deficiency (n=1). Significant differences in the effects of rhGH on pubertal timing were found by clinical indication. Only among children with ISS, rhGH promoted earlier age at pubertal timing (mean difference=-0.46 years; 95% CI, -0.90 to -0.03; 9 studies; n total=402) or higher relative risk for pubertal onset during study follow-up (1.26; 95% CI, 1.03 to 1.54; 6 studies; n total=284). Conclusions Treatment with rhGH appears to promote earlier pubertal timing among children with ISS. Evidence was lacking in children with growth hormone deficiency due to the absence of studies with untreated controls.

BackgroundLevels of steroid hormones in the first three months of life, a period referred to as ‘mini-puberty’, are one of the earliest physiological differences between typical males and females postnatally. Autistic traits also show consistent typical sex differences in later infancy, after the 18th month of life. Previous studies have shown prenatal testosterone is associated with later levels of autistic traits. Studies testing if postnatal testosterone levels are associated with autistic traits have reported null results. No studies to date have investigated mini-puberty longitudinally or tested for interactions with baseline sex differences or familial likelihood of autism.MethodsThe ‘Cambridge Human Imaging and Longitudinal Development Study’ (CHILD) is a prospective enriched cohort study in Cambridge, UK. It includes physiological measurements in early infancy, as well as neurodevelopmental follow-ups over the first two years of life. A subset of the cohort also includes children with a family history of autism (a diagnosed parent or sibling). Salivary testosterone levels were assessed at two time-points, just after the 2nd and 6th month of life. Autistic traits were measured using the Quantitative Checklist of Autism in Toddlers (Q-CHAT) when the children were 18 months of age.ResultsSalivary testosterone levels were significantly higher during ‘mini-puberty’ in the 2nd and 3rd month of life, compared to after the 6th month of life, in both males and females. There was no significant sex difference at either time-point. Log-transformed testosterone levels were not associated with autistic traits (Q-CHAT). There was no interaction effect with infant sex, autism family history or baseline testosterone levels after mini-puberty (at >6 months of age).ConclusionBoth male and female infants have elevated levels of salivary testosterone during mini-puberty but in this relatively small sample this was not associated with their later autistic traits at 18 months or their family history of autism. This suggests that prenatal rather than postnatal testosterone levels are more relevant for understanding the causes of autism. Future studies should test these relationships in larger samples.

Unlike mammals, teleost fish have high aromatase activity (AA) in the pituitary. However, the cells responsible for oestradiol synthesis and the local physiological roles of this hormone remain unclear. Hence, we investigated the effects of age and development on steroidogenic activity, mRNA expression, and cyp19a1b localization in the pituitary gland of the Japanese pufferfish Takifugu rubripes. Under aquaculture conditions, AA was highest after puberty, and the mRNA expression levels of cyp19a1b and the oestrogen receptors esr1 and 2b and the level of serum testosterone (T) were significantly increased after puberty compared with the other developmental stages in male and female pufferfish. Immunohistochemistry using multiple antibodies and in situ hybridization analysis revealed that Cyp19a1b colocalizes with luteinizing hormone (LH) in pituitary cells. Furthermore, Esr1 was localized in the nuclei of all hormone-producing cells, whereas Esr2b was localized only in the nuclei of Cyp19- and LH-positive cells. The administration of an aromatizable androgen (T) or oestrogen (E2) to reproductively inactive females induced LH synthesis in vivo. We prepared spheroids from pituitary cells to investigate the role of local E2 in LH synthesis in vitro. Immunohistochemical analysis of spheroids showed that T-induced LH synthesis could be blocked by an aromatase inhibitor and/or an ER antagonist but not an AR antagonist. Taken together, these findings suggest that LH synthesis is initiated in cyp19a1b-, esr1-, and esr2b-expressing cells at the onset of puberty under the control of steroidal feedback, and both feedback and local oestrogen may be involved in controlling LH synthesis in these cells.

This study investigated the puberty-related health needs of 10-5-year-old boys in Iran. The literature shows that the growing health problems of adolescents are an important health issue worldwide. The present study was a cross-sectional descriptive survey that applied a stratified-cluster sampling technique to collect data from boys aged 10-15 years in order to assess puberty-related health problems. The survey used a self-reported questionnaire comprising 10 demographic questions with 35 research questions based on five categories: awareness of puberty changes, mood swings, sexual orientation, self-confidence, and health behaviors. Five questions examined education demands. The study used descriptive statistics, chi-square test, regression, and correlation coefficient for quantitative data analysis. The mean age of the adolescents was 11.38 ± ± 4.37 years. There was a significant link between the maternal and paternal educational level and awareness of puberty changes among adolescent boys (p 0.001). Overall, 69.81% of teenage boys lacked puberty awareness and had not understood puberty and health behaviors, and 87% of the teenage boys had no access to desired educational resources. At the same time, 82% of the boys' families did not disclose puberty changes and hygiene practices. The results indicated a significant positive correlation between adolescents' health behaviors and awareness of puberty changes (r = 0.12 p 0.007). The results also revealed a positive relationship between self-confidence and health behaviors (r = 0.14, p 0.001). There is a need among adolescent boys to receive health-related information about puberty. Teenage boys' families play an indispensable role in educating adolescents about puberty and health-related changes.

Introduction Bone age (BA) is a quantitative determination of skeletal maturation. The role of puberty in variations in BA is poorly understood as hypothalamic-pituitary-gonadal (HPG) axis maturation and skeletal maturation are regulated in parallel but independently by multiple different factors. In countries like India where there is rapid nutrition transition and increase in prevalence of obesity, their impact on height and BA is not well understood. Objectives To study if in 2–17 year old healthy children, the difference between chronological age (CA), height age (HA) and BA is less than 1 year on either side of the chronological age and to assess relationship of BA with height, weight and BMI with special reference to gender and puberty. Methods This cross-sectional study included 804 preschool/school-going Indian children. Anthropometric measurements and pubertal assessments were performed using standard protocols and were converted to age and sex standardized z-scores using Indian references while BA was estimated by Tanner-Whitehouse (TW3) method. p Results The mean age and gender standardized z-scores for height, weight, body mass index (BMI) and BA were −0.3 ± 0.7, −0.7 ± 0.8, −0.1 ± 1.0, and −0.2 ± 0.9 respectively. HA was more delayed in girls while BA was more delayed in boys. The mean BA z-score increased with increasing BMI. After the onset of puberty, there was higher increment in BA in girls and HA in boys (p Conclusions HA, BA and CA were tightly correlated in healthy Indian children with a significant role of nutritional status and puberty in causing variation in the same.

Osteoporosis-pseudoglioma syndrome (OPPG; MIM #259770) is a rare autosomal recessively inherited disease, characterized by early-onset osteoporosis and congenital blindness, caused by loss-of-function mutations in the LRP5 gene. Beneficial effects of bisphosphonate treatment in patients with OPPG are well known, while follow-up data on growth and pubertal parameters are limited. This article provides clinical follow-up data and long-term bisphosphonate treatment results in four OPPG patients from three unrelated families, ranging between 2.5 and 7 years of age at presentation. Clinical diagnosis was molecularly confirmed in all patients, with four different germline biallelic LRP5 mutations including a novel nonsense variant c.3517CT (p.(Gln1173*)) in two siblings with marked phenotypic variability. Anthropometric and pubertal data and bone mineral density (BMD) measurements were evaluated retrospectively. Early puberty was observed in two patients. The bisphosphonate treatment duration of patients varied around 4-7 years and improvement in BMD z-scores with bisphosphonate treatment was demonstrated in all patients (z-score changes were +5.6, +4.0, +1.0, and +1.3). Although further research is needed to identify the possible association between early puberty and OPPG, all OPPG patients should be followed up with detailed endocrinological evaluation regarding pubertal status.

Purpose Adolescence represents an important window for gonadal development. The aim of this review is to carry out a critical excursus of the most recent literature on endogenous and exogenous risk factors related to testicular function, focusing the research on adolescence period. Methods A comprehensive literature search within PubMed was performed to provide a summary of currently available evidence regarding the impact on adolescence of varicocele, cryptorchidism, cancer, diabetes, lifestyle factors, endocrine disruptors, obesity and sexually transmitted diseases. We focused on human studies that evaluated a possible impact of these factors on puberty timing and their effects on andrological health. Results Evidence collected seems to suggest that andrological health in adolescence may be impaired by several factors, as varicocele, cryptorchidism, and childhood cancer. Despite an early diagnosis and treatment, many adolescents might still have symptoms and sign of a testicular dysfunction in their adult life and at the current time it is not possible to predict which of them will experience andrological problems. Lifestyle factors might have a role in these discrepancies. Most studies point out towards a correlation between obesity, insulin resistance, alcohol, smoking, use of illegal drugs and testicular function in pubertal boys. Also, endocrine disruptors and sexually transmitted diseases might contribute to impair reproductive health, but more studies in adolescents are needed. Conclusion According to currently available evidence, there is an emerging global adverse trend of high-risk and unhealthy behaviors in male adolescents. A significant proportion of young men with unsuspected and undiagnosed andrological disorders engage in behaviors that could impair testicular development and function, with an increased risk for later male infertility and/or hypogonadism during the adult life. Therefore, adolescence should be considered a key time for intervention and prevention of later andrological diseases.

Based on the Differential Susceptibility Theory, we examined whether the relationship between pubertal maturation and depressive symptoms can be moderated by individual differences in environmental sensitivity. The current article used the three-wave data collected from Japanese adolescents aged from 12 to 15 years (girls = 111, boys = 98). Consequently, a significant Sensitivity × Pubertal Development interaction was observed in 12- to 13-year-old boys, but not girls. Sensitive boys who experienced accelerated physical maturation reported decreased depressive symptoms, while those who experienced less maturation had increased depressive symptoms. The shape of the interaction supported both the Differential Susceptibility Theory and the Diathesis-Stress Model. Our findings suggest that sensitivity during early puberty among boys could be reconsidered as susceptibility rather than vulnerability.

Introduction Increased fiber intake has been associated with decreased breast cancer risk, while increased animal protein intake with increased risk. The objective of this study is to examine the relationship of dietary fiber and protein intake to estrogen and sex hormone–binding globulin (SHBG) concentrations at puberty onset. Methods These analyses were conducted using the Cincinnati puberty cohort of the Breast Cancer and the Environment Research Program, with girls followed every 6 months from ages 6 and 7. The analyses included serum measurements at 6-month intervals for estrogen and SHBG concentrations, from 18 months prior to breast stage 2 (onset of puberty). Dietary intake was documented via 24-hour dietary recalls every 3 months. Dietary factors of interest included total energy intake; total and animal protein; total, soluble, and insoluble fiber; and lignan and flavanol intake. Results This study included 260 participants who generated 871 serum specimens and 3,000 days of diet intake. In longitudinal models, estradiol was associated inversely with insoluble fiber intake; estrone positively with animal protein intake; SHBG with greater insoluble fiber and lower total protein intake; and ratio of estrone to SHBG, a measure of bioavailable estrogen, positively with animal protein. Conclusions Greater protein intake, especially animal protein, led to greater estrogen concentrations and lower SHBG; greater animal protein and greater caloric intake led to increased bioavailable estrogen. This relationship may have served an evolutionary advantage in the past for greater fertility with adequate high-quality protein; in contemporary women, a modest decrease in animal protein may be beneficial in reducing breast cancer risk.

Background Heavier body mass index (BMI) is the most established predictor of earlier age at puberty. However, it is unknown whether the timing of the childhood switch to heavier BMI (age at BMI rebound) also matters for puberty. Methods In the LEGACY Girls Study (n = 1040), a longitudinal cohort enriched with girls with a family history of breast cancer, we collected paediatric growth chart data from 852 girls and assessed pubertal development every 6 months. Using constrained splines, we interpolated individual growth curves and then predicted BMI at ages 2, 4, 6, 8 and 9 years for 591 girls. We defined age at BMI rebound as the age at the lowest BMI between ages 2 and 8 years and assessed its association with onset of thelarche, pubarche and menarche using Weibull survival models. Results The median age at BMI rebound was 5.3 years (interquartile range: 3.6–6.7 years). A 1-year increase in age at BMI rebound was associated with delayed thelarche (HR = 0.90; 95% CI = 0.83–0.97) and menarche (HR = 0.86; 95% CI = 0.79–0.94). The magnitude of these associations remained after adjusting for weight between birth and 2 years, was stronger after adjusting for BMI at age 9, and was stronger in a subset of girls with clinically assessed breast development. Conclusions Earlier BMI rebound is associated with earlier pubertal timing. Our observation that BMI rebound may be a driver of pubertal timing in girls with and without a family history of breast cancer provides insight into how growth and pubertal timing are associated with breast cancer risk.

Throughout the 20 century, in developed countries there has been a secular trend toward earlier menarche. Over the past 2 decades, however, there has been an apparent stabilization in the average age of menarche age in most Western countries.The objective of this study was to analyze the mean age of menarche in a cohort of Italian girls, to analyze the mean age of breast button appearance (B2), and to correlate the B2 developmental stage and age at menarche with the most important clinical and auxological parameters.We retrospectively evaluated the data of 1458 Italian girls born between 1995 and 2003. We collected the main auxological and clinical parameters, including age at B2, age at menarche, height, weight, and body mass index (BMI) at B2 and menarche and, when possible, adult/near adult height.The mean age of B2 was 10.16 ± 1.00 years, significantly earlier than previously reported for Italian girls (P.05); the mean age of menarche was 12.07 ± 0.99 years, also significantly earlier than previously reported (P.0001). Age at B2 and menarche inversely correlated with BMI standard deviation score (SDS) (P.0001). The mean adult/near adult height of the girls in the study cohort was not statistically different from previously reported data for Italian women.Our results suggest a new trend for an earlier appearance of thelarche and menarche in Italian girls. Our data confirm a significant relationship between BMI and age of B2 and menarche. The girls' final height seems to be in line with average height for the Italian female population.

Pediatric endocrinologists often evaluate and treat youth with delayed puberty. Stereotypically, these patients are 14-year-old young men who present due to lack of pubertal development. Concerns about stature are often present, arising from gradual shifts to lower height percentiles on the population-based, cross-sectional curves. Fathers and/or mothers may have also experienced later than average pubertal onset. In this review, we will discuss a practical clinical approach to the evaluation and management of youth with delayed puberty, including the differential diagnosis and key aspects of evaluation and management informed by recent review of the existing literature. We will also discuss scenarios that pose additional clinical challenges, including: (1) the young woman whose case poses questions regarding how presentation and approach differs for females vs males; (2) the 14-year-old female or 16-year-old young man who highlight the need to reconsider the most likely diagnoses, including whether idiopathic delayed puberty can still be considered constitutional delay of growth and puberty at such late ages; and finally (3) the 12- to 13-year-old whose presentation raises questions about whether age cutoffs for the diagnosis and treatment of delayed puberty should be adjusted downward to coincide with the earlier onset of puberty in the general population.

The present study explored young adolescent’s (female at birth) experiences with their bodies following pubertal changes. Twenty-seven participants selected from a parent-daughter workshop at school who had experienced 1 to 6 menstrual cycles were interviewed. Data were collected and analysed using interpretative phenomenological analysis. Four current themes emerged from the analysis: (i) perception of body changes in puberty; (ii) intense emotions; (iii) managing body changes and secondary sexual characteristics; (iv) a new way of experiencing the body. Results support an integrative approach to the prevention of body negative image. Based on these findings, it is important to considered body image in the complexity of its emotional, cognitive and behavioural manifestations in order to promote psycho-educational programmes related to secondary sexual characteristics, consistent with the needs of today’s pubertal female at birth.

Multiple studies indicate that adult male rodents perform better than females on spatial problems and have a lower threshold for long-term potentiation (LTP) of hippocampal, CA3-to-CA1 synapses. We report here that in rodents, prepubescent females rapidly encode spatial information and express low threshold LTP, while age-matched males do not. The loss of low threshold LTP across female puberty was associated with three inter-related changes: increased densities of α5 subunit-containing GABA(A)Rs at inhibitory synapses, greater shunting of burst responses used to induce LTP, and a reduction of NMDAR-mediated synaptic responses. A negative allosteric modulator of α5-GABA(A)Rs increased burst responses to a greater degree in adult than in juvenile females and markedly enhanced both LTP and spatial memory in adults. The reasons for the gain of functions with male puberty do not involve these mechanisms. In all, puberty has opposite consequences for plasticity in the two sexes, albeit through different routes.

ObjectiveAlthough exposure to abuse in early life predicts earlier pubertal timing, especially for girls, it is unclear if this association generalizes to nonabuse stressors. In addition, the impact of race on the stress-maturation association remains unknown. To address these issues, we examined whether race moderates the effects of early adversity on pubertal timing and tempo using a longitudinal study design.MethodsIn a cohort of 9- and 10-year-old Black and White girls, pubertal (areolar and pubic hair) maturation was assessed annually for 7 years. In adulthood, 368 participants (186 Black, 182 White) reported on abuse and nonabuse stressors they experienced from ages 0 to 12 years.ResultsEarly life abuse was associated with earlier pubertal timing, as indexed by younger age at menarche (b = -0.22, p = .005, 95% confidence interval [CI] = -0.39 to -0.06) and greater pubic hair development (b = 0.11, p = .003, 95% CI = 0.04 to 0.18), in addition to slower pubertal tempo, as indexed by slower rate of pubic hair (b = -0.03, p < .001, 95% CI = -0.05 to -0.01) and areolar (b = -0.02, p = .02, 95% CI = -0.03 to -0.003) development. These associations were not found for nonabuse adversity. Black girls with early life abuse had greater pubic hair development (b = 0.23, p < .001, 95% CI = 0.12 to 0.35) and were slower in pubic hair tempo (b = -0.07, p < .001, 95% CI = -0.09 to -0.04) than their White counterparts.ConclusionsScreening for early life abuse may help address health disparities related to earlier pubertal timing.

Spanning from bench to bedside, the history of normal and precocious puberty is characterized by a series of remarkable advances that have illuminated reproductive physiology and profoundly impacted clinical care. Early recognition of the hypothalamic and pituitary control of ovarian and testicular function led to the identification of GnRH as the key driver of pubertal onset. Decades later, discovery of the kisspeptin system further refined our understanding of human reproductive neuroendocrinology. Development of long-acting analogs of GnRH revolutionized the treatment of precocious puberty worldwide and ushered in the current era of an ever-expanding therapeutic armamentarium. Identification of monogenic etiologies of precocious puberty has further illustrated the exquisite complexity that comprises neurosecretory modulation of the hypothalamic GnRH neuron and may well lead to exciting novel targeted therapies.

Introduction: Pubertal delay is described as one of the clinical features in Noonan syndrome (NS) and it may be one of the factors causing short adult height in those patients. The present study aimed at characterizing pubertal development in NS and identifying pubertal delay predictors. Methods: We analyzed 133 individuals with a molecular diagnosis of NS and clinical puberty evaluation. We characterized delayed puberty as pubertal onset after 12 years in girls and 13.5 years in boys, according to parameters of the Brazilian population. To investigate its predictors, we correlated the age at onset of puberty with several characteristics and genotype in a multilevel regression model. For comprehending pubertal development in NS, we assessed age and anthropometric measures at each Tanner stage and adult age. Results: The mean age at puberty onset for girls was 11.9 ± 1.9 years and for boys, 12.5 ± 1.7 years, significantly later than the Brazilian population (p = 0.025; p < 0.001). Girls (49.1%) presented delayed puberty more frequently than boys (27.9%, p = 0.031). Body mass index standard deviation scores (SDS) and insulin growth factor 1 SDS at puberty onset significantly predicted later puberty entry. Height gain from the onset of puberty to adult height was lower in children with pubertal delay. Conclusion: Pubertal delay is characteristically found in children with NS, more frequently in females. The low weight of patients with NS could modulate the age of puberty, just as the increase in overweight/obesity in the general population has shown an effect on reducing the age of onset of puberty.

BackgroundBiological aging and particularly the deviations between biological and chronological age are better predictors of health than chronological age alone. However, the predictors of accelerated biological aging are not very well understood. The aim was to determine the role of birth outcomes, time of puberty onset, body mass index (BMI), and body fat in accelerated biological aging in the third decade of life.MethodsWe have conducted a second follow-up of the Czech part of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC-CZ) prenatal birth cohort in young adulthood (52% male; age 28–30; n = 262) to determine the role of birth outcomes, pubertal timing, BMI, and body fat on biological aging. Birth outcomes included birth weight, length, and gestational age at birth. Pubertal timing was determined by the presence of secondary sexual characteristics at the age of 11 and the age of first menarche in women. Biological age was estimated using the Klemera-Doubal Method (KDM), which applies 9-biomarker algorithm including forced expiratory volume in one second (FEV1), systolic blood pressure, glycated hemoglobin, total cholesterol, C-reactive protein, creatinine, urea nitrogen, albumin, and alkaline phosphatase. Accelerated/decelerated aging was determined as the difference between biological and chronological age (BioAGE).ResultsThe deviations between biological and chronological age in young adulthood ranged from −2.84 to 4.39 years. Accelerated biological aging was predicted by higher BMI [in both early (R2adj = 0.05) and late 20s (R2adj = 0.22)], subcutaneous (R2adj = 0.21) and visceral fat (R2adj = 0.25), puberty onset (ηp2 = 0.07), birth length (R2adj = 0.03), and the increase of BMI over the 5-year period between the two follow-ups in young adulthood (R2adj = 0.09). Single hierarchical model revealed that shorter birth length, early puberty onset, and greater levels of visceral fat were the main predictors, together explaining 21% of variance in accelerated biological aging.ConclusionOur findings provide comprehensive support of the Life History Theory, suggesting that early life adversity might trigger accelerated aging, which leads to earlier onset of puberty but decreasing fitness in adulthood, reflected by more visceral fat and higher BMI. Our findings also suggest that reduction of BMI in young adulthood slows down biological aging.

Multi-region pain during adolescence is associated with a higher symptom burden and lower quality of life. The purpose of this study was to describe and compare the biopsychosocial attrib- utes of single-region and multi-region pain among healthy young adolescents. We analyzed data from 10,320 children aged 10.6 to 14 years who self-reported pain in the Adolescent Brain and Cognitive Development Study. Pain was coded as single-region or multi-region based on body map data. One in 5 young adolescents indicated recent multi-region pain. Sequential regression supported improved model fit when psychological and sociocultural factors were added to a biological model of pain; however, these models improved the classification of multi-region but not single-region pain. A significant interaction effect of sex and puberty remained constant across models with increased odds of pain at each advancing pubertal stage for both sexes compared with prepuberty, but no difference between girls and boys at late puberty (adjusted odds ratio [OR] = 2.45 [1.72, 3.49] and adjusted OR = 1.63 [1.20, 2.23], respectively). Psychological factors improved the classification of multi-region pain with significant effects of anxiety, somatic symptoms, and somnolence. Finally, compared with White and non-Hispanic children, Black and Hispanic children were less likely to report pain (adjusted OR = 0.70 [0.61, 0.80]; adjusted OR = 0.88 [0.78, 0.99], respectively) but had significantly higher pain interference when pain was present (adjusted OR = 1.49 [1.29, 1.73] and adjusted OR = 1.20 [1.06, 1.35], respectively). Pain is a biopsychosocial phenomenon, but psychological and sociocultural features may be more relevant for multi-region compared with single-region pain during early adolescence.