Aug 2026· Pediatric Research· 0 citations· 34 references
Medicine
TL;DR
A sex-specific protective effect of puberty on MASLD risk in children, with advancing puberty associated with significantly lower odds of MASLD in boys, but not in girls.
Adrenal androgen activity, reflected by DHEA-S, represents a significant endocrine pathway linking obesity to accelerated skeletal maturation, highlighting developmentally specific windows of endocrine-metabolic interaction in growing children.
Youngha Choi, Eunju Lee, H. Lee et al.· Frontiers in Endocrinology· 0 citations
Abstract Background This study aimed to examine how Body Mass Index (BMI) influences the timing of puberty in girls. Methods This cross-sectional study included students from urban and rural areas of Isfahan Province, Iran. Breast development was assessed by visual inspection and palpation and pubic hair development was evaluated using Tanner’s Sexual Maturation Scale. Participants reported the month and year of menarche. Median ages for each pubertal stage were estimated using probit modelling, and analyses were performed separately by BMI category (underweight, normal weight, overweight and obese). Results A total of 13 886 girls aged 6–18 years participated. According to WHO cut-offs, 61.9% were normal weight, 9.5% underweight, 13.1% overweight, 15.5% obese and 50.2% had experienced menarche. The onset of breast development (≥B2) occurred earliest in overweight (9.59 years) and obese (9.68 years) girls, followed by normal-weight (9.87 years) and underweight (10.61 years) participants. A similar trend was observed across subsequent Tanner stages and pubic hair development. Median age at menarche was 11.62 years in obese girls, 11.76 years in overweight, 12.04 years in normal-weight and 13.15 years in underweight participants. Overall, girls with higher BMI reached pubertal milestones and menarche earlier than their normal-weight and underweight peers. Conclusions Higher BMI in girls is associated with earlier onset of puberty and menarche. These findings highlight the impact of childhood overweight and obesity on pubertal development and underscore the importance of monitoring growth and weight status to anticipate and manage potential health consequences.
Maryam Esmaeili, Mohammad Reza Maracy, Roya Kelishadi et al.· BMJ Paediatrics Open· 0 citations
PURPOSE
The primary objective of this study is to elucidate the role of age at menarche in depression in adulthood and explore the implications of this association.
METHODS
We conducted a study involving 9,826 adult female participants from the National Health and Nutrition Examination Survey (NHANES) between 2015 and August 2023. Age at menarche was categorized as early (<12 years), normal (12-14 years), or late (≥15 years). Depression was assessed using the 9-item Patient Health Questionnaire (PHQ-9) and clinical diagnoses. Logistic regression and restricted cubic spline analyses were performed to address the study objectives. In addition, subgroup analyses were conducted based on demographic, lifestyle, and clinical characteristics.
RESULTS
The depression group had a significantly higher proportion of young adults (aged 18-30 years) compared to the nondepression group (26.46% vs. 20.52%, p < .001). Conversely, the nondepression group included a greater proportion of older adults (over 60 years) than the depression group (29.53% vs. 23.98%, p < .001). After comprehensive adjustments, early menarche was significantly associated with increased depression risk (adjusted odds ratio [aOR] = 1.224, 95% confidence interval [CI]: 1.003-1.493, p = .047). Restricted cubic spline analyses revealed an L-shaped nonlinear pattern (p for nonlinearity = 0.006), with optimal age at menarche around 12 years. Subgroup analyses confirmed consistent associations without significant interactions.
DISCUSSION
Early menarche is linked to increased depression risk, especially among women aged 18-30 years. Menarche at 12 years may serve as a key point for early intervention to prevent depression in young women.
Qiannan Liu, Renke He, Yizhuo Miao et al.· Journal of Adolescent Health· 0 citations
BACKGROUND
Metabolic dysfunction-associated steatotic liver disease (MASLD) and male hypogonadism are increasingly prevalent, metabolically interrelated conditions. Testosterone (T) deficiency has been implicated in hepatic lipid dysregulation, insulin resistance, and visceral adiposity, whereas MASLD may impair the hypothalamic-pituitary-gonadal axis. We conducted a systematic review and meta-analysis to evaluate the bidirectional association between circulating T levels and MASLD in adult men.
METHODS
Following PRISMA guidelines, a literature search was performed from inception to July 31, 2025. Twenty-eight studies met the inclusion criteria (9 comparing hypogonadal vs. eugonadal men; 19 comparing MASLD vs. non-MASLD men). Random-effects models were used to pool effect sizes for dichotomous and continuous outcomes. Meta-regression analyses assessed the influence of age, anthropometric features, glycemic markers, liver enzymes, and hormonal parameters.
RESULTS
Hypogonadal men showed a significantly higher prevalence of MASLD than eugonadal men (p = 0.001) and exhibited higher fatty liver index scores (p < 0.001). Total T concentrations were significantly lower in men with MASLD than in controls (p = 0.014). Meta-regression analyses did not identify significant effects of study-level differences in age, body mass index, or biochemical variables on the observed associations. Sex hormone-binding globulin levels were also significantly reduced in MASLD (p < 0.001), with age emerging as the only significant modifier. No significant differences were observed for luteinizing hormone, estradiol, or fibrosis-4 index. Across studies evaluating MASLD severity, moderate-to-severe disease was associated with lower T levels, particularly in analyses based on imaging.
CONCLUSIONS
This meta-analysis supports a clinically relevant association between testosterone deficiency and MASLD, although evidence for the bidirectional nature of this relationship remains asymmetric but supports a clinically relevant endocrine-hepatic axis. T deficiency appears independently linked to MASLD onset and severity beyond the effects of age and adiposity. These findings underscore the need for reciprocal screening of liver health and gonadal status in at-risk men and highlight the importance of prospective studies and randomized trials to determine whether correcting T deficiency may modify MASLD progression.
G. Spaggiari, L. Valentina, C. Felicani et al.· Andrology· 0 citations
BACKGROUND
CYP19A1 encodes aromatase, the enzyme converting androgens to estrogens, thereby influencing breast tissue development in healthy children.
OBJECTIVE
To examine associations between CYP19A1 single nucleotide polymorphisms (SNPs) and circulating estradiol (E2), testosterone (T), the E2/T ratio, and age at thelarche in girls, and presence of gynecomastia in boys.
METHODS
A total of 1023 healthy participants (aged 5.9-20.0 years) from the Copenhagen Puberty Study were assessed for pubertal status and serum sex steroid concentrations were measured by LC-MS/MS. Genotyping of CYP19A1 SNPs (rs727479 A>C, rs2899472 A>C, rs10046 C>T) was performed.
RESULTS
Girls with AA genotype in rs727479 and rs2899472 showed tendencies toward earlier pubertal onset. In a combined efficacy-allele model, each additional allele was associated with 1.6 months earlier puberty (p = 0.06), and girls with 5-6 vs. 0-2 efficacy alleles presented with significantly lower pubertal age (p = 0.02). CYP19A1 genotype was not associated with E2, T, or E2/T levels. Boys with CC genotype in rs727479 had the highest prevalence of pubertal gynecomastia (73%, p < 0.01). Boys with gynecomastia showed higher E2 and T (SDS) than unaffected boys (both p < 0.01), with no difference in E2/T. In age-matched analyses, E2 (SDS) remained elevated in boys with gynecomastia (0.81 vs. 0.19, p = 0.04).
CONCLUSION
CYP19A1 variants may influence pubertal timing in girls. In boys, pubertal gynecomastia appeared to be linked with CYP19A1 genotype and was associated with elevated E2 concentrations.
SIGNIFICANCE STATEMENT
Aromatase, encoded by CYP19A1, catalyzes the conversion of androgens to estrogens. The contribution of common CYP19A1 genetic variants to variation in pubertal development in healthy children is not fully understood. In this cohort from the Copenhagen Puberty Study, we examined associations between CYP19A1 polymorphisms, circulating sex steroid concentrations, age at puberty and pubertal gynecomastia in boys. By integrating genetic, hormonal, and clinical pubertal data, this study provides additional insight into potential links between aromatase-related genetic variation and normal pubertal development.
Veronica L R Groendahl, S. A. Holmboe, A. Busch et al.· Endocrine Connections· 0 citations
Background: Hormonal alterations, may complicate the metabolic consequences linked to childhood obesity. To study the relation between pediatric obesity and hormonal abnormalities, along with the correlation between body mass index (BMI) and other metabolic and endocrine markers.
Methods: A prospective observational study including 325 children aged 6 to 14 years was conducted at a tertiary care teaching hospital in north India over 30 months (January 2024 to July 2026). Individuals were classified into three categories based on their BMI percentiles for age and gender as normal weight, overweight, and obese. In addition to blood pressure and anthropometric data, fasting biochemical markers such as cortisol, free thyroxine (free T4), glucose, insulin, and thyroid-stimulating hormone (TSH) were measured. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated to determine insulin resistance. One-way analysis of variance and multivariate linear regression with age and gender adjustments were used for statistical analysis.
Results: Obese children demonstrated markedly elevated levels of cortisol, TSH, HOMA-IR, and fasting insulin compared to their normal-weight counterparts, along with reduced levels of free T4 (p<0.05). A multivariate regression analysis, after controlling for age and gender, indicated that BMI was significantly associated with indicators of insulin resistance and thyroid hormone levels.
Conclusions: Childhood obesity is associated with significant hormonal and metabolic alterations, suggesting early endocrine adaptations that may have metabolic implications. While these changes (particularly thyroid-related shifts) represent reversible, adaptive responses rather than primary pathology, findings highlight need for early identification and intervention to prevent potential long-term cardiometabolic risks associated with pediatric-onset obesity.
Rakhi Jain, P. Upadhyay· International Journal of Con...· 0 citations
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