Impact of feeding age on cognitive impairment in mice with Disrupted-In-Schizophrenia 1 (Disc1) mutation under a high sucrose diet.

A combination of genetic predisposition and environmental factors contributes to the development of psychiatric disorders such as schizophrenia, bipolar disorder and major depressive disorder. Previous studies using mouse models suggested that prolonged high sucrose intake during puberty can serve as an environmental risk factor for the onset of psychiatric disorders. However, the impact of both the duration and timing of high sucrose consumption during different developmental stages on pathogenesis remains poorly defined. We therefore investigated the effects of a long-term high sucrose diet on cognitive deficit, a core symptom of psychiatric disorders, using Disrupted-in-Schizophrenia 1 locus-impairment heterozygous mutant (Disc1het) mice as a model for genetic predisposition. First, Disc1het mice and their littermate control (WT) were fed either a high sucrose diet or a control starch diet for nine weeks starting at weaning (postnatal day 24), and tested for cognitive performance in the object location test (OLT) and the novel object recognition test (NORT) (assessing spatial and recognition memory, respectively). Only Disc1het mice on a high sucrose diet displayed deficits in OLT (p < 0.0001), demonstrating impaired hippocampus-dependent spatial memory. This behavioral abnormality was accompanied by a decreased proportion of the high parvalbumin-expressing interneurons (High-PV neurons) in the ventral hippocampus, a cell type that regulates neural activity and a variety of learning and memory processes such as spatial and working memory. We further explored the critical developmental period for high sucrose intake to cause cognitive deficits in adulthood by comparing specific feeding periods during puberty (P24-P65) and post-puberty (P65-P90). Compared to those on a standard chow diet, high sucrose intake caused deficits in spatial memory in both WT and Disc1het mice, with more pronounced effects in Disc1het mice. In particular, Disc1het mice on a sucrose diet during adolescence showed more pronounced cognitive deficit than those fed after adolescence. Our results suggest that adolescence is particularly vulnerable to nutritional environmental risk factors, and that high sucrose consumption may cause hippocampus-dependent memory deficits via decreased High-PV interneuron function when combined with Disc1-related genetic predisposition.

Association of screen exposure/sedentary behavior and precocious puberty/early puberty.

Background: In recent years, with the development of society, children's daily exposure to screen time has gradually increased. Screen exposure and sedentary behavior have brought a host of harms to children's lives. The aim of this study was to explore the effects of screen exposure and sedentary behavior on precocious puberty and early development. Methods: This is a cross-sectional study in the school-based population. A total of 3,560 children were recruited from Qufu City, Shandong province using multistage stratified cluster random sampling. All study subjects had a physical examination by professional pediatricians in October 2019, and were investigated with health questionnaires. Precocious puberty is defined as development of secondary sexual signs in boys before 9 years or in girls before 8 years. Screen time was calculated as the average of screen time on weekdays and weekend days, and sedentary time was calculated as the average of sedentary time on weekdays and weekend days. After adjusting for potential confounders, logistic regression was used to examine the association between screen exposure and sedentary behavior and early puberty and precocious puberty. Results: Sedentary time was a risk factor for precocious puberty and early development (OR = 1.428, 95% CI = 1.087-1.876) in girls without adjustment. No significant association was found between screen exposure and early puberty and early development both in girls and boys. Conclusions: Excessive sedentary behavior was associated with an increased risk of early puberty, especially in girls, while there was no significant association between screen exposure and early puberty and early development. In addition, further longitudinal investigations are needed to determine the causal relationship between screen exposure, sedentary behavior and precocious puberty.

Selective depletion of kisspeptin neurons in the hypothalamic arcuate nucleus in early juvenile life reduces pubertal LH secretion and delays puberty onset in mice.

Puberty is the critical developmental transition to reproductive capability driven by the activation of gonadotropin-releasing hormone (GnRH) neurons. The complex neural mechanisms underlying pubertal activation of GnRH secretion still remain unknown, yet likely include kisspeptin neurons. However, kisspeptin neurons reside in several hypothalamic areas and the specific kisspeptin population timing pubertal onset remains undetermined. To investigate this, we strategically capitalized on the differential ontological expression of the Kiss1 gene in different hypothalamic nuclei to selectively ablate just arcuate kisspeptin neurons (aka KNDy neurons) during the early juvenile period, well before puberty, while sparing RP3V kisspeptin neurons. Both male and female transgenic mice with a majority of their KNDy neurons ablated (KNDyABL) by diphtheria toxin treatment in juvenile life demonstrated significantly delayed puberty onset and lower peripubertal LH secretion than controls. In adulthood, KNDyABL mice demonstrated normal in vivo LH pulse frequency with lower basal and peak LH levels, suggesting that only a small subset of KNDy neurons is sufficient for normal GnRH pulse timing but more KNDy cells are needed to secrete normal LH concentrations. Unlike prior KNDy ablation studies in rats, there was no alteration in the occurrence or magnitude of estradiol-induced LH surges in KNDyABL female mice, indicating that a complete KNDy neuronal population is not essential for normal LH surge generation. This study teases apart the contributions of different kisspeptin neural populations to the control of puberty onset, demonstrating that a majority of KNDy neurons in the arcuate nucleus are necessary for the proper timing of puberty in both sexes.

Association between Changes in Menarcheal Age and Adolescent Idiopathic Scoliosis: An Analysis of 38,879 Patients over 20 Years.

Backgroud: Menarche has a significant impact on the progression of adolescent idiopathic scoliosis (AIS); however, studies in this area are insufficient. This study used large-scale school screening data to investigate the relationship between menarcheal age and AIS, especially the severity of scoliosis. Methods: Of 2,326,577 students who participated in school screening for scoliosis (SSS) in South Korea from 2001 to 2021, 38,879 girls with AIS, who experienced menarche, were included. Data including the patient's demographics, such as menarcheal age, Cobb angle, Risser stage, and the interval between menarche and the time of screening were retrieved from the SSS database. Pearson correlation coefficient was used to identify the changes in menarcheal age according to the birth year and to investigate the relationship between menarcheal age and each variable of interest. Results: Based on the birth year, the mean menarcheal ages in girls with AIS from 1988 to 2008 demonstrated a steadily decreasing trend over time (r = -0.857, p < 0.001). Girls with AIS and late menarche demonstrated a higher Cobb angle at the time of screening (r = 0.095, p < 0.001). Other variables did not significantly correlate with menarcheal age. Conclusions: Based on the SSS, a large-scale school screening dataset, menarcheal age in girls with AIS demonstrated an ongoing downward trend in the recent 20 years in South Korea. Notably, girls with AIS and late menarche had a higher Cobb angle at screening. Our findings indicate the need for earlier screening of AIS in girls who have not undergone menarche.

Prenatal phthalate exposure and pubertal development in 16-year-old daughters: reproductive hormones and number of ovarian follicles.

STUDY QUESTION: Is there a possible association between prenatal phthalate exposure and late effects in teenage daughters with respect to reproductive hormone levels, uterine volume, and number of ovarian follicles? SUMMARY ANSWER: Our study showed subtle associations between phthalate metabolite concentrations in maternal serum from pregnancy or cord blood and LH and insulin-like growth factor 1 (IGF-1) levels as well as uterine volume in their daughters 16 years later. WHAT IS KNOWN ALREADY: Endocrine-disrupting environmental chemicals may adversely affect human reproductive health, and many societies have experienced a trend toward earlier puberty and an increasing prevalence of infertility in young couples. The scientific evidence of adverse effects of foetal exposure to a large range of chemicals, including phthalates, on male reproductive health is growing, but very few studies have explored effects on female reproduction. STUDY DESIGN, SIZE, DURATION: This follow-up study included 317 teenage daughters who were part of the Copenhagen Mother-Child Cohort, a population-based longitudinal birth cohort of 1210 females born between 1997 and 2002. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 317 female participants (median age 16 years) were examined for weight, height, and menstrual pattern. A serum sample was analysed for concentrations of reproductive hormones, and trans-abdominal 3D ultrasonography was performed to obtain the number of ovarian follicles, ovarian and uterine size. Prenatal maternal serum samples were available for 115 females, and cord blood samples were available for 118 females. These were analysed for concentrations of 32 phthalate metabolites. Weighted quantile sum regression was used for modelling associations of combined prenatal phthalate exposure with the reproductive outcomes in post-menarcheal females. MAIN RESULTS AND THE ROLE OF CHANCE: In bivariate correlation analyses, negative significant associations were found between several prenatal phthalate metabolite concentrations and serum hormone concentrations (testosterone, 17-OH-progesterone, and IGF-1) as well as number of ovarian follicles in puberty. Positive significant correlations were found between prenatal phthalate exposure and FSH and sex hormone-binding globulin concentrations. Combined analyses of phthalate exposure (weighted quantile sums) showed significant negative associations with IGF-1 concentration and uterine volume as well as a significant positive association with LH concentration. LIMITATIONS, REASONS FOR CAUTION: Phthalate metabolites were measured in serum from single prenatal maternal blood samples and cord blood samples. Potential concomitant exposure to other endocrine-disrupting environmental chemicals before or after birth was not controlled for. The study population size was limited. WIDER IMPLICATIONS OF THE FINDINGS: Our results support the need for further research into possible adverse effects of environmental chemicals during foetal development of the female reproductive system. STUDY FUNDING/COMPETING INTEREST(S): The work was supported by The Center on Endocrine Disruptors (CeHoS) under The Danish Environmental Protection Agency and The Ministry of Environment and Food (grant number: MST-621-00 065). No conflicts of interest are declared. TRIAL REGISTRATION NUMBER: N/A.

Revising LH cut-off for the diagnosis of central precocious puberty via triptorelin stimulation assay.

INTRODUCTION: Precocious puberty (PP) in girls is defined by thelarche before age 8. The diagnostic gold standard is an increased LH level following gonadotropin-releasing hormone (GnRH) stimulation. Alternatively, GnRH analogues like triptorelin can be used, though their interpretation varies. Since 2000, we have used a triptorelin-induced LH cut-off of 15 IU/L, 4 h post-stimulus. However, many girls showed LH values below this threshold despite evident pubertal progression. PURPOSE: To establish a new LH threshold post-triptorelin stimulation for earlier diagnosis of central precocious puberty (CPP) in girls showing pubertal progression and to evaluate additional parameters for diagnostic accuracy. METHODS: We enrolled 186 girls with thelarche onset between ages 1-8 and a GnRH analogue assay performed between 2015-2019 without signs of axis activation. Within this cohort, 62 patients repeated the triptorelin test due to rapid pubertal progression. The assay involved administering 100 mcg/m² of triptorelin and measuring LH, FSH, and estradiol levels before and four hours post-injection. RESULTS: Patients with axis activation at the second test had significantly higher post-stimulus LH levels at the first test compared to those below 15 IU/L. They also had higher basal LH levels, elevated LH/FSH ratio, and increased growth velocity. Statistical analysis identified a new post-stimulus LH threshold of 5 IU/L. CONCLUSION: We propose a LH value of 5 IU/L after triptorelin administration as a new threshold for early CPP diagnosis. While the LH/FSH ratio and growth velocity are associated with axis activation, they did not significantly enhance diagnostic accuracy when combined with the LH value.

Two tiers, not one: Different sources of extrinsic mortality have opposing effects on life history traits.

Guided by concepts from life history (LH) theory, a large human research literature has tested the hypothesis that exposures to extrinsic mortality (EM) promote the development of faster LH strategies (e.g., earlier/faster reproduction, higher offspring number). A competing model proposes that, because EM in the past was intimately linked to energetic constraints, such exposures specifically led to the development of slower LH strategies. We empirically address this debate by examining (1) LH variation among small-scale societies under different environmental conditions; (2) country-, regional- and community-level correlations between ecological conditions, mortality, maturational timing, and fertility; (3) individual-level correlations between this same set of factors; and (4) natural experiments leveraging the impact of externally-caused changes in mortality on LH traits. Partially supporting each model, we found that harsh conditions encompassing energetic stress and ambient cues to EM (external cues received through sensory systems) have countervailing effects on the development of LH strategies, both delaying pubertal maturation and promoting an accelerated pace of reproduction and higher offspring number. We conclude that, although energetics are fundamental to many developmental processes, providing a first tier of environmental influence, this first tier alone cannot explain these countervailing effects. An important second tier of environmental influence is afforded by ambient cues to EM. We advance a 2-tiered model that delineates this second tier and its central role in regulating development of LH strategies. Consideration of the first and second tier together is necessary to account for the observed countervailing shifts toward both slower and faster LH traits.

A Phase 3, Open-Label, Single-Arm Trial of the Efficacy and Safety of Triptorelin 6-Month Formulation in Chinese Children with Central Precocious Puberty.

INTRODUCTION: This phase 3 study assessed the efficacy, safety, and pharmacokinetics of the 6-month prolonged release (PR) formulation in Chinese children with central precocious puberty (CPP). METHODS: In this open-label study (NCT05029622), Chinese children (girls < 9 years, boys < 10 years) received two doses of triptorelin pamoate 22.5 mg (day 1 and month 6). Primary endpoint was the proportion at month 6 with luteinizing hormone (LH) suppression (stimulated peak LH ≤ 5 IU/L after gonadotropin-releasing hormone stimulation). Secondary endpoints included safety assessments, hormone level changes, and clinical parameters from baseline. RESULTS: Overall, 66 children completed the study (93.9% girls; median age 8.0 [range 5-9] years). At month 6, all patients had LH suppression; this was maintained at month 12 in 98.5% of patients. Mean basal and peak LH and follicle-stimulating hormone levels were suppressed throughout follow-up. All patients at months 3 to 12 had sex hormone suppression to prepubertal levels. Stable or reduced breast development was seen for 98.4% and 93.5% of girls at month 6 and 12, respectively; all boys had regression or stable genital development until month 12. Compared with baseline (9.82 cm/year), mean growth velocity was 5.88 cm/year at month 6 and 5.17 cm/year at month 12. Mean bone age/chronological age ratio decreased from 1.27 at baseline to 1.23 and 1.21 at month 6 and 12, respectively. In girls, 64.5% showed decreased uterine length at month 6 and 12 versus baseline, while 75.0% of boys showed stable testicular volume versus baseline. Thirteen patients (19.7%) had 22 drug-related treatment emergent adverse events (TEAEs); no grade ≥ 3 TEAEs were reported. CONCLUSION: The efficacy and safety profile of triptorelin 6-month PR in Chinese children with CPP was consistent with data previously reported in non-Chinese children with CPP, supporting this as a viable treatment option for Chinese children with CPP. TRIAL REGISTRATION: Trial registration: ClinicalTrials.gov identifier, NCT05029622.

WHAT IS CENTRAL PRECOCIOUS PUBERTY (CPP)?: CPP is a condition where reproductive organs and sexual characteristics develop too early, before the age of 8 years in girls or 9 years in boys. CPP can negatively affect the mental health of patients and their caregivers. It can also lead to long-term problems like obesity and diabetes. CPP is caused by high levels of a hormone called luteinizing hormone. HOW IS CPP TREATED?: Triptorelin is an injectable treatment that can lower luteinizing hormone levels. Triptorelin injections are available for use once every month, once every 3 months, or once every 6 months. The injection for use once every 6 months (the 6-monthly injection) is not currently approved for CPP treatment in China. WHAT DID THIS STUDY LOOK AT?: This study assessed how well the 6-monthly triptorelin injections worked in 66 Chinese children with CPP. One injection was given at the start of the study and one after 6 months. WHAT WERE THE RESULTS?: Six months after their first injection, all children had luteinizing hormone levels that were below those seen with CPP. The development of sexual characteristics had slowed, such as pubic hair growth, breast and uterine length for girls, and testicular volume for boys. In addition, the rate at which children were increasing in height had also slowed down. These treatment effects were also seen at 12 months (6 months after the second injection). No children stopped treatment because of side effects. The researchers concluded that 6-monthly triptorelin may be a good treatment option for Chinese children with CPP.

Osteocalcin: may be a useful biomarker for early identification of rapidly progressive central precocious puberty in girls.

OBJECTIVE: To assess serum osteocalcin (OC) as a potential biomarker for the early detection of rapidly progressive central precocious puberty (RP-CPP) in girls. METHODS: Serum OC levels were quantified using enzyme-linked immunosorbent assays (ELISAs). In the retrospective analysis, receiver operating characteristic (ROC) curve analysis was employed to evaluate the ability of OC to identify RP-CPP. A prospective study and screening tests were utilized to assess the potential of OC for use in the early prediction of RP-CPP. Variable selection in the multivariate analysis was conducted using the Bayesian Information Criterion (BIC) and binary logistic regression was employed to construct the diagnostic prediction model. RESULTS: Girls with RP-CPP had significantly higher serum OC levels compared to girls with non-rapidly progressive central precocious puberty (NRP-CPP) (149.04±40.50 vs. 89.10±31.83 ng/mL, P < 0.001). The optimal OC cut-off point for differentiating RP-CPP from NRP-CPP was 107.05 ng/mL, the area under the ROC curve (AUC) was 0.90 (95%CI: 0.851-0.949; P < 0.001), with a sensitivity of 91.1% and specificity of 70.7%. The results of the prospective study indicated that changes in OC precede alterations in estradiol (E2) and bone age (BA). A diagnostic prediction model that includes duration of breast development, BA, OC, high-density lipoprotein cholesterol (HDL-C), and uterine length achieved an AUC of 0.961, with a sensitivity of 94.1% and specificity of 91.5% for the detection of RP-CPP. If OC is excluded from the model, the AUC decreases to 0.894, with sensitivity and specificity declining to 80.5% and 83.1%, respectively. CONCLUSIONS: Serum OC levels may serve as a promising biomarker for the early differentiation between RP-CPP and NRP-CPP in girls. The diagnostic prediction model that incorporates duration of breast development, BA, OC, HDL-C, and uterine length effectively identifies girls with RP-CPP.

Immunosuppressive Therapy, Puberty and Growth Outcomes in Pediatric Kidney Transplant Recipients: A Pragmatic Review.

Kidney transplantation in children with end-stage kidney disease significantly enhances survival and quality of life but poses unique challenges related to chronic immunosuppressive therapy. In fact, despite being essential for preventing organ rejection, immunosuppressive therapy can have significant side effects specific to pediatric patients, such as adverse impacts on physiological growth, puberty, and fertility. The resulting short stature and delayed or incomplete pubertal development can profoundly affect young patients' psychological and social well-being, impacting self-esteem and overall quality of life, and may significantly hamper compliance and therapeutic adherence. Most studies on immunosuppression in pediatric kidney transplant recipients focus on general side effects and outcomes like long-term graft survival or acute complications. On the other side, there is limited evidence in the current literature on the specific issues of growth, puberty, and fertility in this patient population. In this pragmatic review, we aimed to summarize the most relevant information available on these critical aspects of post-transplant management in pediatric patients, also providing some practical indications on management strategies for minimizing these often neglected but still important complications.

MCM9 compound heterozygosity in an adolescent with premature ovarian insufficiency.

Summary: Delayed puberty in girls is often related to late maturation but is occasionally the first sign of premature ovarian insufficiency (POI). POI is a condition that affects ovarian function and fertility, and its etiology is unknown in most cases. Genetic factors have recently been identified in 20-25% of women with POI, involving genes that regulate various aspects of ovarian development and maintenance. We report a case of delayed puberty due to POI in an adolescent from a non-consanguineous family who carried two variants in the MCM9 gene. MCM9 is essential for DNA replication and repair, and its dysfunction can lead to chromosomal instability and ovarian failure. Our case highlights the importance of targeted gene panel analysis, particularly in POI patients with negative autoimmunity screening, and evidence of ovarian or uterine dysgenesis on pelvic imaging. Learning points: Delayed puberty in girls is often self-limiting, but it can also indicate underlying conditions with lifelong implications, such as premature ovarian insufficiency (POI). Patients with POI, negative autoimmune screening, a normal karyotype, and no FMR premutation should undergo further genetic testing, preferably through targeted gene panels. Compound heterozygous variants in MCM9 can cause POI, presenting with delayed puberty and primary amenorrhea in girls without a consanguineous family.

Amygdala Subregion Volumes and Apportionment in Preadolescents - Associations with Age, Sex, and Body Mass Index.

Importance: The amygdala, a key limbic structure, plays a critical role in emotional, social, and appetitive behaviors that develop throughout adolescence. Composed of a heterogeneous group of nuclei, questions remain about potential differences in the maturation of its subregions during development. Objective: To characterize the associations between developmental variables and amygdala subregion volumes during preadolescence. Design Setting and Participants: Cross-sectional Adolescent Brain Cognitive Development (ABCD®) Study data was collected from 3,953 9- and 10-year-old children between September 1, 2016, and October 15, 2018. Data analysis was conducted between June 1, 2023, and July 30, 2024. Main Outcomes and Measures: Using the CIT168 Amygdala Atlas, nine amygdala subregion volumes were quantified from high-quality MRI scans. Linear mixed-effects models were used to examine the effects of age, sex, pubertal stage, and body mass index z-score (BMIz) on subregion volumes and their relative apportionment within the amygdala. Results: The study population consisted of 3,953 preadolescents (mean [SD] age, 120 [7.41] months; 1,763 [44.6%] female; 57 [1.4%] Asian, 527 [13.3%] Black, 740 [18.7%] Hispanic, 2,279 [57.7%] white, and 350 [8.9%] from other racial/ethnic groups [identified by parents as American Indian/Native American, Alaska Native, Native Hawaiian, Guamanian, Samoan, other Pacific Islander, or other race]). Distinct associations were observed between age, sex, and BMIz and whole amygdala volume, subregion volumes, and subregion apportionment. Pubertal stage was not related to amygdala subregion volumes. Age was associated with near-global expansion of amygdala subregions during this developmental period. Female sex was linked to smaller volumes in most amygdala subregions, with larger relative apportionment in dorsal amygdala subregions and smaller apportionment in the basolateral ventral paralaminar subregion. Higher BMIz was associated with smaller volumes in large laterobasal subregions, with increased relative apportionment in smaller subregions. Conclusions and Relevance: This cross-sectional study suggests that age, but not pubertal stage, is associated with near-global expansion of the amygdala at ages 9 and 10, while sex and BMIz are linked to distinct changes in amygdala subregions that explain observed differences in total volumes. These findings provide a foundational context for understanding how developmental variables influence amygdala structure in preadolescents, with implications for understanding future risk for brain disorders.

Too late or too soon? The replacement gilt paradox.

Due to high annual culling rates, pig farms require a constant income of replacement gilts. Gilts typically reach puberty at nearly six months of age. Puberty may be induced through early boar exposure, therapy with steroid hormones and chorionic gonadotropins, and optimized by identifying biological predictors and risk factors. Old age at the time of the first mating is associated with an increased risk of premature culling, often attributed to reproductive failures and locomotor problems. While female prolifacy has increased substantially during the last few decades, selecting for litter size to optimize lifetime productivity would be more efficient after two parities. Additionally, uterine capacity and the number of functional teats should be considered in selecting future dams. For each female, the cost-effective number of parities at removal is determined by the cumulative number of pigs born and weaned during the total herd days.

ADHD and Risk of Precocious Puberty: Considering the Impact of MPH.

BACKGROUND/OBJECTIVES: The complex association between attention-deficit/hyperactivity disorder (ADHD) and methylphenidate (MPH) with precocious puberty (PP) is still unclear. This study aims to investigate the association between ADHD, MPH, and PP. METHODS: This is a nationwide cohort study including a total of 3,342,077 individuals, 186,681 with ADHD and 3,155,396 without. First, we compared the risk of PP between ADHD cases and non-ADHD cases. Second, we compared the risk of PP between MPH users and non-MPH users in patients with ADHD. RESULTS: Patients with ADHD were at a greater risk of PP (adjusted hazard ratio [aHR], 2.01 [95% CI, 1.91-2.11]). In our moderation analyses, the female gender was a positive additive effect modifier of the association between ADHD and PP, whereas tics and intellectual disability were negative effect modifiers. In patients with ADHD, MPH users had a significantly lower risk of PP (aHR, 0.63 [95% CI 0.57-0.70]), and females had a negative effect modification on the association between MPH and PP. CONCLUSIONS: Our study found that children with ADHD were at a greater risk of PP. Girls with ADHD were a group particularly vulnerable to PP. Comorbid tics or intellectual disability was associated with a lower risk of PP. Among patients with ADHD, MPH was protective against PP, especially in girls. However, these preliminary results need further validation due to the nature of them being from an electronic database study. Unmeasured confounding factors might affect the association between MPH and PP.

Community Awareness and Knowledge About Precocious Puberty in Riyadh City, Saudi Arabia.

Background Puberty is the process of physical maturation where an adolescent reaches sexual maturity and becomes capable of reproduction. On average, puberty typically begins between 8 and 13 years old in females and 9 and 14 years old in males. The traditional definition of precocious puberty is the development of secondary sexual characteristics before eight years of age in girls and nine years in boys. In this study, we aimed to assess the knowledge and awareness of Riyadh residents in Saudi Arabia about precocious puberty and its complications. Methodology A cross-sectional study was conducted to estimate the awareness and knowledge among Riyadh residents about precocious puberty and its complications; 426 participants were included in this study. Participants completed a pretested self-administered questionnaire that included sociodemographic data, knowledge about precocious puberty definition, risk factors, complications, and treatment. Results This study enrolled 426 participants. Overall, 10.1% were correct about the precocious puberty age for girls, and 8.5% knew about the precocious puberty age for boys. The overall mean knowledge score among the study sample was 5.56 (SD = 2.79), with poor knowledge being prominent and constituting 68.8%, while fair and good knowledge were 30% and 1.2%, respectively. Working in a non-medical field was the sole independent significant predictor of incorrect answers of knowledge about precocious puberty. Conclusions Awareness strategies are needed to increase awareness among the community to encourage prevention and treatment for precocious puberty as the awareness and knowledge of Riyadh residents in Saudi Arabia about precocious puberty and its complications are low.

The natural course of bone mineral density in transgender youth before medical treatment; a cross sectional study.

OBJECTIVE: Bone mineral density (BMD) Z-scores decrease during puberty suppression in transgender youth. Assessment of treatment impact has been based on the assumption that without intervention, BMD Z-scores remain stable. However, the natural course of BMD in this population is unknown. DESIGN: Retrospective cross-sectional study. METHODS: Dual-energy X-ray absorptiometry scans prior to medical intervention were included from 333 individuals assigned male at birth (AMAB) and 556 individuals assigned female at birth (AFAB) aged 12-25 years. The relationship between age and BMD Z-scores of sex assigned at birth was analysed for the lumbar spine (LS), total hip (TH), femoral neck (FN), and total-body-less-head (TBLH), adjusted for height SDS, height-adjusted lean mass Z-score, and whole body percentage fat Z-score. RESULTS: In individuals AMAB, the BMD Z-score was negatively associated with age between 12 and 22 years: LS -0.13/year (95% confidence interval, CI -0.17; -0.10); TH -0.05/year (95% CI -0.08; -0.02); FN -0.06/year (95% CI -0.10; -0.03); and TBLH -0.12/year (95% CI -0.15; -0.09). Adjusting for height-adjusted lean mass Z-score attenuated the association at the LS and TBLH and eliminated the association at the TH and FN. BMD Z-scores and age were not associated between 22 and 25 years. In individuals AFAB, BMD Z-scores were only associated with age at the TBLH (-0.08/year, 95% CI -0.12; -0.04) between age 12 and 20 years. CONCLUSION: In individuals AMAB aged 12-22 years prior to any treatment, BMD Z-scores were inversely correlated with age. This could imply that BMD increases less in individuals AMAB than in the general population, and that changes in Z-score during puberty suppression and subsequent hormone supplementation are not necessarily due to treatment, but possibly related to lifestyle factors.

Potential Role of Sleep Disturbance in the Development of Early Puberty: Past Clinical Evidence for Future Management.

The incidence of early puberty in children has been increasing. It has been suspected that both genetic and various environmental factors such as nutrition and hormonal exposure could influence the mechanisms underlying the earlier onset of puberty. Interestingly, several previous studies have reported a strong connection between sleep and puberty. Specifically, it was discovered that luteinizing hormone (LH), a potential marker for the onset of puberty, was increased during the deep sleep period. Furthermore, a high prevalence of early puberty was observed in patients with sleep disorders, especially in those experiencing narcolepsy. In this review article, findings related to the association between sleep disturbance and early puberty have been comprehensively summarized. Any contrary findings are also included and discussed. Advances in the knowledge surrounding sleep disturbance have led to a greater understanding of a correlation between early puberty and sleep disorder and provide alternative therapeutic options for the treatment of central precocious puberty in the future.

Puberty interacts with sleep and brain network organization to predict mental health.

Introduction: Along with pubertal development, the transition to adolescence brings about increased risk for sleep disturbances and mental health problems. Functional connectivity of overlapping large-scale brain networks, such as increased connectivity between the default mode and dorsal attention networks, has been reported to relate to both sleep and mental health problems. Clarifying whether pubertal development interacts with sleep disturbances and functional brain networks to predict mental health may provide information to improve the timing and design of interventions targeting sleep disturbances in adolescents. Methods: To examine how pubertal status and tempo relate to sleep disturbances and shape the relationship between sleep disturbances and mental health problems, we harnessed a large sample of children aged 10-14 years from the Adolescent Brain and Cognitive Development (ABCD) Study (N ~ 3,000-10,000). We used graph theoretical tools to probe how pubertal development concurrently interacts with sleep disturbances and brain network organization to predict mental health problems. Results: We found that advanced pubertal status, but not pubertal tempo, predicted sleep disturbances; however, both pubertal status and tempo interact with sleep disturbances to predict mental health problems and engage in three-way interactions with sleep and brain network organization to predict mental health problems. Discussion: Overall, this work suggests that less advanced pubertal status and slower tempo are risk factors for the strongest links between sleep disturbances, brain organization, and mental health problems. Further, our findings speak to the importance of accounting for interactions in the constellation of factors that surround complex behavioral and clinical syndromes, here internalizing and externalizing disorders, and provide new context to consider for targeted interventions.

Lifelong impacts of puberty timing on human plasma metabolic profiles: A metabolome-wide Mendelian randomization study.

AIM: The aim was to investigate the causal relationship between puberty timing and plasma metabolites, accounting for birth weight, childhood and adulthood adiposity. MATERIALS AND METHODS: The meta-analysis of genome-wide association studies (GWAS) for puberty timing was extracted from the ReproGen Consortium, involving 329 345 women of European ancestry. Summary data for 174 plasma metabolites were retrieved from a recently conducted cross-platform GWAS that involved a meta-analysis of three cohort studies (i.e. the Fenland, European Prospective Investigation into Cancer-Norfolk and INTERVAL studies) and three publicly available studies and included up to 86 507 participants. We conducted a two-sample Mendelian randomization (MR) analysis to infer the causal relationship of puberty timing on 174 plasma metabolites, complemented by a two-step and multivariable Mendelian randomization (MVMR) analysis to assess direct and indirect effects. Additionally, summary-level data from the UK Biobank were used for our replication analysis. RESULTS: The results of the two-sample MR provide moderate evidence supporting a causal relationship between puberty timing and 23 of 174 plasma metabolites (i.e. 7 acylcarnitines, 8 amino acids, 2 biogenic amines and 6 lysophosphatidylcholines). Even after single-nucleotide polymorphisms associated with birth weight and childhood adiposity were excluded, causal effects persisted for 16 metabolites (i.e. 8 acylcarnitines, 4 amino acids, 2 biogenic amines and 2 lysophosphatidylcholines). The two-step MR analysis provided evidence that the relationship between puberty timing and plasma metabolites was mediated by adulthood adiposity. Additionally, moderate evidence emerged for an independent causal effect of puberty timing on 10 metabolites through an MVMR analysis (i.e. 5 acylcarnitines, 2 amino acids, 1 biogenic amine, 1 lysophosphatidylcholine and 1 phosphatidylcholine). Furthermore, the replication analysis suggested the robustness of our results. CONCLUSIONS: In summary, our study provides compelling evidence that puberty timing has a causal influence on certain plasma metabolites, although this influence is largely mediated by adulthood adiposity.

Trajectories of personal agency by gender and pubertal development among adolescents in Kinshasa: Longitudinal evidence from the GlobalEarly Adolescent Study.

Background: Empowerment research has largely focused on adult women with little focus on younger adolescents. Additionally, despite recognition that empowerment is a process, few studies have longitudinally explored its development. Methods: We used secondary data from four waves of the Global Early Adolescent Study to explore trajectories in the development of three domains of agency (i.e. the internal processes composing empowerment) - Freedom of Movement, Voice, and Decision-Making - for 1188 boys and 1153 girls in Kinshasa, Democratic Republic of Congo. Respondents were age 10-14 at enrollment and followed through age 14-18. We created scales for each domain and conducted gender- and age-stratified latent growth curve modeling with random effects, comparing age 10-14 to age 15-18, accounting for clustering within individuals over waves. We examined the role of puberty within each domain in the analysis of age 10-14. Results: Scores across all domains increased with age for boys and girls, with the exception of Voice amongst boys 10-14. Rates of change varied by age group and gender; for boys, scores increased at a faster rate for older boys relative to younger boys for Freedom of Movement (ß(10-14): 3.98 versus ß(15-18): 6.12) and Voice (ß(10-14): .50 versus ß(15-18): 2.54). Relative to younger girls, scores amongst older girls increased at a faster rate for Freedom of Movement (ß(10-14): 1.76 versus ß(15-18): 3.72) and a slower rate for Decision-Making (ß(10-14): 6.41 versus ß(15-18): 2.80). Puberty was associated with significant increases in scores across all domains for both genders, with the exception of Decision-Making for girls. Interpretation: Young people develop/acquire different forms of agency at different stages of adolescence and development is not uniform across forms. Gender inequalities in agency amplify at puberty, signaling the need to intervene at or before this critical stage of development.