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.

Contraception options during pubertal transition: Risks, benefits and considerations.

BACKGROUND: The age of puberty and sexual maturation has been decreasing, highlighting the importance of providing appropriate contraception to girls and adolescents. However, challenges remain, including legal implications and understanding the effects of hormonal methods on pubertal development. OBJECTIVE: This article aims to equip general practitioners with the knowledge of options, as well as their use and limitations, in young people seeking contraception. DISCUSSION: No one-size-fits-all approach exists for adolescent contraception. Long-acting reversible contraceptives offer superior contraceptive efficacy, with subdermal implants being the most acceptable regarding the insertion procedure. Condoms should be recommended for protection against sexually transmissible infections. Bone health and mood disorders should be considered when prescribing hormonal contraceptives. Despite the lack of robust evidence regarding harm caused by contraception in adolescents, preventing unintended pregnancies should take precedence, with theoretical risks guiding tailored options for individuals.

Reliability of self-reported pubertal development scale for girls in early adolescent: a school population-based study.

OBJECTIVES: The study aimed to evaluate the correlation between self-reported pubertal developmental scale (PDS) and physically assessed Tanner staging by an experienced pediatrician among girls. METHODS: In a school population-based study in Zhongshan, China, we recruited 1,722 girls in grades 1-3 by a multistage stratified cluster random sampling method. Participants completed self-reported PDS questionnaire prior to physical examination. Breast development was evaluated by a female pediatrician combined with ultrasound examination for overweight/obese girls; pubic hair development was evaluated. Otherwise, we tested follicle-stimulating hormone (FSH) and luteinizing hormone (LH) for some participants. RESULTS: We observed a weak association between Tanner-derived composite stage (TDCS) and puberty category scores (PCS) (τ=0.288, p<0.001) among all girls. There was correlation (τ=0.314, p=0.001) between ultrasound-derived composite stage (UDCS) and PCS among overweight/obese girls. Moreover, among overweight/obese girls, PCS was positively correlated with LH (r=0.265, p=0.008), but not FSH (r=0.155, p=0.123), and when the basal LH value was greater than 0.3 mIU/mL, the proportion of PCS stage ≥2 (9/18) was higher than the proportion of TDCS ≥2 (5/18). As for the determination of pubertal onset, when UDCS was used as the gold standard, the specificity of PCS was 0.86 and positive predictive value was 90.00 %. CONCLUSIONS: There was a weak correlation between PCS and TDCS among girls early adolescence. Moreover, among overweight/obese girls, combining hormone values, ultrasonographic stage of breast, and the positive predictive value of PCS, we posit that self-reported PDS might be a more reliable method than TDCS to evaluate pubertal development among overweight/obese girls.

Puberty changes the natural history of idiopathic scoliosis: three prediction models for future radiographic curve severity from 1563 consecutive patients.

PURPOSE: Understanding idiopathic scoliosis (IS) natural history during growth is essential for shared decision-making between patients and physicians. We developed a retrospective model with the largest available sample in the literature and we aimed to investigate if using three peri-pubertal growth periods provides better prediction than a unique model. METHODS: Secondary analysis of a previous study on IS natural history data from radiographs before and at the first consult. Three groups: BEFORE (age 6-10), AT (age 11-Risser 2) and AFTER (from Risser 3) the pubertal growth spurt. Available predictors: Cobb angle, curve type, sex, observation time, and Risser score. We used linear mixed-effects models to predict future Cobb angles in each group. We internally validated prediction accuracy with over 100 patients per group (3 to 5-fold cross-validation). RESULTS: We included 1563 participants (275 BEFORE, 316 AFTER, 782 females and 190 males AT). Curves increased over time mostly in AT, importantly in BEFORE, but also in AFTER. All models performed better than the general one. In BEFORE, 74.2% of the predictions were within ± 5o, 71.8% in AFTER, 68.2% in AT females, and 60.4% in males. The predictors (baseline curve, observation time also squared and cubic, and Risser score) were similar in all the models, with sex influencing only AFTER. CONCLUSION: IS curve severities increase differently during growth with puberty stages. Model accuracy increases when tailored by growth spurt periods. Our models may help patients and clinicians share decisions, identify the risk of progression and inform treatment planning.

Higher peak height velocity in early maturing girls depends on insulin rather than fat mass or IGF-I.

OBJECTIVE: Age at pubertal onset has decreased over the recent decades. Early maturing girls have longer puberty duration, and higher peak height velocity (PHV) than late maturing girls. To what extent this is generated by increased insulin-like growth factor-I (IGF-I), fat mass, or fasting insulin levels is currently unknown. DESIGN, SETTING, PARTICIPANTS: A population-based study-part of the COPENHAGEN puberty study-longitudinal part. Eighty-one girls evaluated biannually for a median of 10 (2-15) visits for a total of 815 evaluations. METHODS: Pubertal staging, anthropometric measures, PHV, skin fold thickness (SFT), and IGF-I and fasting insulin levels were measured. RESULTS: Early maturing girls achieved similar final height compared to late maturing girls (166.1 vs 167.1 cm, P = .36). Early pubertal onset was associated with significantly greater PHV (8.7 vs 7.4 cm/year, P < .001) and a longer puberty duration (age at onset of breast development to age at PHV [1.8 vs 1.1 years, P < .001]) compared with late maturation. After correcting for age at pubertal onset, neither body mass index, SFT, nor IGF-I levels differed between early vs late maturing girls. By contrast, fasting insulin levels were significantly higher in early compared with late maturing girls 1.5, 2.0, and 3.0 years after pubertal onset (all P = .039). CONCLUSION: Growth velocity was higher and more prolonged in early compared with late maturing girls and associated with higher insulin levels. Thus, the higher insulin levels may compensate for the shorter total growth period by intensifying the pubertal growth period. CLINICAL TRIAL REGISTRATION NUMBER: NCT01411527.

Tendon structure, clinical tests, and pain during-loading in young female competitive gymnasts.

To examine the relationship between Achilles-tendon (AT) and patellar-tendon (PT) structure, clinical-examination and tendon pain in young gymnasts; and, to explore the associations between these factors and age, maturation, and training-load. Two hundred and seventy-four female gymnasts (aged 12.1±1.9 yrs) were assessed for anthropometric measures, pubertal-stage, and training-load. They had clinical-tests (pain-on-palpation for AT and pain-on-palpation and Royal-London Hospital-Test for PT), were asked about tendon-pain during-loading and were assessed for tendon-structure. Gymnasts with positive clinical-tests (with and without pain during-loading) presented a significantly higher prevalence of disorganized AT and PT compared to gymnasts with negative clinical-tests (with and without pain during-loading) (p<0.05). A significant pubertyXpositive clinical-test interaction was found for disorganized PT structure, whereby a disorganized structure was more prevalent among post-pubertal gymnasts with positive clinical-tests compared to pre-pubertal participants with negative clinical-tests (F(1, 263)=9.436, p=0.002). In gymnasts with positive clinical-tests, significant correlations were found between disorganized AT and PT structures and age, and training-load (p<0.05). An increased prevalence of disorganized tendon structure (regardless of pain during-loading) was seen in participants with positive clinical-tests. This disorganized tendon-structure was found to be significantly related to increased age, post-pubertal stage, and higher training hours in gymnasts with positive clinical-tests.

Coming of age in war: Early life adversity, age at menarche, and mental health.

Armed conflict and forced migration (ACFM) represent a set of extreme environments that are increasingly common for children and adolescents to experience. Adolescence may constitute a sensitive period (puberty and psychoneurological maturation) through which ACFM adversity leaves a lasting mark. Adolescence has become a focal point for analysis and intervention as it relates to the effects of early life adversity on puberty, linear growth, and mental health. Research in public health and psychological science suggests early life adversity (ELA) may accelerate puberty, heightening risks for mental health disorders. However, it is not well substantiated whether ACFM-derived adversities accelerate or delay relative pubertal timing. Secondly, ACFM provides salient context through which to probe the relationships between nutritional, psychosocial, and demographic changes and their respective impact on puberty and mental health. We conducted a narrative review which 1) examined constructions of early life adversity and their proposed influence on puberty 2) reviewed empirical findings (n = 29 studies, n = 36 samples) concerning effects of ACFM ELA on age at menarche and 3) discussed proposed relationships between early life adversity, puberty, and mental ill-health. Contrary to prior research, we found war-derived early life adversity was more consistently associated with pubertal delay than acceleration and may exert counterintuitive effects on mental health. We show that ELA cannot be operationalized in the same way across contexts and populations, especially in the presence of extreme forms of human stress and resilience. We further discuss the ethics of puberty research among conflict-affected youth.

Sibling relatedness and pubertal development in girls and boys: A population-based cohort study.

PURPOSE: To investigate the association between sibling relatedness and pubertal development in girls and boys. METHODS: This cohort study consisted of 10,657 children from the Puberty Cohort, Denmark. Information on sibling relatedness was obtained by self-report. Information on pubertal markers was obtained half yearly from age 11 and throughout puberty. Mean age difference at attaining pubertal markers was estimated using interval-censored regression models according to sibling relatedness (full, half and/or step siblings; half and/or step siblings; no siblings; relative to full siblings). RESULTS: Girls with both full, half and/or step siblings (-1.2 (CI 95 %: -2.5; 0.1) months), only half- and/or stepsiblings (-2.2 (CI 95 %: -3.7; -0.7) months), and no siblings (-5.5 (CI 95 %: -8.5; -2.5) months) entered puberty earlier than girls with full siblings. Boys with full, half and/or step siblings (-1.4 (CI 95 %: -2.7; -0.1) months), only half and/or step siblings (-1.2 (CI 95 %: -3.0; 0.6) months), and no siblings (-4.5 (CI 95 %: -8.8; -0.3) months) entered puberty earlier than boys with full siblings. CONCLUSIONS: Children with sibling relatedness other than full siblings entered puberty earlier than their peers with full siblings even after adjustment for parental cohabitation status, childhood body mass index and childhood internalizing and externalizing symptoms.

"Sexual Development": Timing Puberty in German Enlightenment Medicine (1778-99).

From the mid-eighteenth century onward, French vitalists started to re-theorize the bodily clock of maturation. Archaic notions of precocity as an ill omen and ancient constructions of sexual timing as ethnic markers now acquired an increasingly physiological profile. Regulatory conceptions of sexual and psychosexual "development" widely animated German literature in the closing decades of the century. Here is evidence of new interdisciplinary problematizations of pubescence (Mannbarkeit) as the coordination in time of the mental apparatus (Seele, Character) and the sex drive (Geschlechtstrieb). New developmental-physiological frames for sexual maturity and psychosexuality readily extended to the fate of Nationalcharacter, sponsoring various roundtables concerning etiological questions.

À partir du milieu du XVIIIe siècle, les vitalistes français ont commencé à théoriser à nouveau l'horloge corporelle de la maturation. Les représentations archaïques de la précocité, considérée comme un mauvais présage, et les anciennes constructions du calendrier sexuel, perçues sous l'angle des marqueurs ethniques, ont acquis un profil de plus en plus physiologique. De fait, les conceptions réglementaires du « développement ¼ sexuel et psychosexuel ont largement animé la littérature allemande au cours des dernières décennies du XVIIIe siècle. On y trouve des preuves de nouvelles problématisations interdisciplinaires de la puberté (Mannbarkeit) en tant que coordination dans le temps de l'appareil mental (Seele, Character) et de la libido (Geschlechtstrieb). Les nouveaux cadres développementaux et physiologiques de la maturité sexuelle et de la psychosexualité ont également influencé le Nationalcharacter, qui a parrainé diverses tables rondes sur les questions étiologiques.

Neural adaptation to changes in self-voice during puberty.

The human voice is a potent social signal and a distinctive marker of individual identity. As individuals go through puberty, their voices undergo acoustic changes, setting them apart from others. In this article, we propose that hormonal fluctuations in conjunction with morphological vocal tract changes during puberty establish a sensitive developmental phase that affects the monitoring of the adolescent voice and, specifically, self-other distinction. Furthermore, the protracted maturation of brain regions responsible for voice processing, coupled with the dynamically evolving social environment of adolescents, likely disrupts a clear differentiation of the self-voice from others' voices. This socioneuroendocrine framework offers a holistic understanding of voice monitoring during adolescence.

Changes in the Bile Acid Pool and Timing of Female Puberty: Potential Novel Role of Hypothalamic TGR5.

CONTEXT: The regulation of pubertal timing and reproductive axis maturation is influenced by a myriad of physiologic and environmental inputs yet remains incompletely understood. OBJECTIVE: To contrast differences in bile acid isoform profiles across defined stages of reproductive maturity in humans and a rat model of puberty and to characterize the role of bile acid signaling via hypothalamic expression of bile acid receptor populations in the rodent model. METHODS: Secondary analysis and pilot studies of clinical cohorts, rodent models, ex vivo analyses of rodent hypothalamic tissues. Bile acid concentrations is the main outcome measure. RESULTS: Lower circulatory conjugated:deconjugated bile acid concentrations and higher total secondary bile acids were observed in postmenarcheal vs pre-/early pubertal adolescents, with similar shifts observed in infantile (postnatal day [PN]14) vs early juvenile (PN21) rats alongside increased tgr5 receptor mRNA expression within the mediobasal hypothalamus of female rats. 16S rRNA gene sequencing of the rodent gut microbiome across postnatal life revealed changes in the gut microbial composition predicted to have bile salt hydrolase activity, which was observed in parallel with the increased deconjugated and increased concentrations of secondary bile acids. We show that TGR5-stimulated GnRH release from hypothalamic explants is mediated through kisspeptin receptors and that early overexpression of human-TGR5 within the arcuate nucleus accelerates pubertal onset in female rats. CONCLUSION: Bile acid isoform shifts along stages of reproductive maturation are conserved across rodents and humans, with preclinical models providing mechanistic insight for the neuroendocrine-hepatic-gut microbiome axis as a potential moderator of pubertal timing in females.

Proposed complementary osteological indicators: Advancing the estimation of puberty stages in Bioarcheology.

OBJECTIVES: The study of puberty is a well-established area of bioarcheological research, which greatly enhances our understanding of adolescence and growth in the past. Since the publications of Shapland and Lewis' works, which have become "standards" for estimating puberty in skeletal material, no additional osteological indicators of puberty have been proposed. Nevertheless, clinical practice constantly develops skeletal maturation markers that could be useful in bioarcheology. This study aims to assess the applicability and reliability of novel puberty indicators as a complementary tool to estimate puberty in skeletal remains. MATERIALS AND METHODS: Four new maturation markers including spheno-occipital synchondrosis, humeral head ossification, calcaneal apophysis ossification, and mandibular premolar mineralization were selected and applied to a sample of 85 adolescents from pre-Roman southern Italy (Pontecagnano, 7th-4th BCE). RESULTS: Despite some limits in adapting the original clinical methods to osteoarcheological material, the use of these novel skeletal indicators had moderate to excellent scoring repeatability and an overall high agreement with the puberty and menarche status previously estimated with standard methods. These results encourage us to apply these markers in bioarcheology. In some cases, minor adaptations of the original scoring systems are suggested to enhance reliability. DISCUSSION: Including the proposed indicators in routine puberty data collection allows us to refine puberty estimation and improve the ability to identify key growth milestones in poorly preserved skeletons. Further application to osteological collections with diverse chronology and geographical differences is needed to assess how and to what extent the newly proposed maturation markers perform.

Adolescent boys' aggressive responses to perceived threats to their gender typicality.

When adult men are made to feel gender-atypical, they often lash out with aggression, particularly when they are pressured (vs. autonomously motivated) to be gender-typical. Here, we examined the development of this phenomenon. Specifically, we provided a first experimental test of whether threatening adolescent boys' perceived gender typicality elicits aggression as a function of their pressured (vs. autonomous) motivation to be gender-typical. We also investigated whether this causal link emerges as a function of boys' chronological age versus pubertal development. Participants were a geographically diverse sample of 207 adolescent US boys (ages 10-14; 23.2% boys of color) and one of their parents. Boys played a "game" and received randomly-assigned feedback that their score was atypical versus typical of their gender. For boys in mid-to-late puberty (but not before), feedback that they are gender-atypical predicted an aggressive reaction, particularly among boys whose motivation to be gender-typical was pressured (vs. autonomous). Next, we explored which aspects of boys' social environments predicted their pressured motivation to be gender-typical. Boys' pressured motivation was positively correlated with their perceptions that their parents and peers would be "upset" if they deviated from gender norms, as well as with their parents' endorsement of so-called hegemonic beliefs about masculinity (i.e., that men should hold power over women). Parents with these beliefs resided in more conservative areas, had less formal education, and had lower incomes. Our results inform theorizing on gender identity development and lay the foundation for mitigating the harmful effects of gender typicality threat among adult men. RESEARCH HIGHLIGHTS: Similar to young adult men, adolescent boys in mid-to-late puberty (but not before) responded with aggression to perceived threats to their gender typicality. Aggression was heightened among boys whose motivation to be gender-typical was pressured (i.e., driven by social expectations) rather than autonomous. Which boys showed pressured motivation? Those whose parents endorsed hegemonic beliefs about masculinity (e.g., that men should have more power than people of other genders). Hegemonic beliefs about masculinity were strongest among parents who resided in more conservative US counties, had less formal education, and had lower incomes.

Puberty suppression in adolescents with gender dysphoria: an emerging issue with multiple implications.

Controversy exists over puberty suppression (PS) in adolescents with gender dysphoria (GD). PS is preferentially achieved with GnRH analogues. By preventing the development of secondary sex characteristics, PS may improve psychological functioning, well-being, quality of life, emotional and behavioral (especially internalizing) problems and depressive symptoms, thus decreasing suicidality. PS can also extend the diagnostic period and give transgender adolescents time to explore their gender identity. GnRHa may also decrease the need for feminization/masculinization surgery. However, 2-year treatment with GnRHa may result in bone mass accrual retardation (decrease in BMD/BMAD z-scores), growth velocity deceleration (decrease in height SDS), increase in fat mass, temporary pause in oocyte/sperm maturation. The most common side effects of GnRHa are hot flashes, mood fluctuations, fatigue and headache. They are usually mild and rarely lead to GnRHa discontinuation. Based on current scientific evidence, PS could be recommended to adolescents who meet the diagnostic criteria of gender incongruence (by DSM-5 and/or ICD-11) and have long-lasting intense GD, which aggravates with puberty onset. Before initiating PS, possible mental issues should be addressed and informed consent (by the adolescent/caregiver) should be given, after counseling on probable reproductive effects of GnRHa. GnRHa can only be started after the adolescent has entered Tanner stage 2. Nevertheless, published studies are inadequate in number, small in size, uncontrolled and relatively short-term, so that it is difficult to draw safe conclusions on efficacy and safety of GnRHa. Large long-term randomized controlled trials are needed to expand knowledge on this controversial issue and elucidate the benefit and risks of PS.

Within-person biological mechanisms of mood variability in childhood and adolescence.

Mood variability, the day-to-day fluctuation in mood, differs between individuals and develops during adolescence. Because adolescents show higher mood variability and average mood than children and adults, puberty might be a potential biological mechanism underlying this increase. The goal of this preregistered developmental study was to examine the neural and hormonal underpinnings of adolescent-specific within-person changes in mood variability, with a specific focus on testosterone, cortisol, pubertal status, and resting-state functional brain connectivity. Data from two longitudinal cohorts were used: the L-CID twin study (aged 7-13, N at the first timepoint = 258) and the accelerated Leiden Self-Concept study (SC; aged 11-21, N at the first timepoint = 138). In both studies resting-state functional magnetic resonance imaging (rs-fMRI) data was collected, as well as daily mood. Additionally, in the SC study self-reported puberty testosterone and cortisol were collected. Random intercept cross-lagged panel models (RI-CLPM) were used to study the within-person relations between these biological measures and mood variability and average mood. Mood variability and average mood peaked in adolescence and testosterone levels and self-reported puberty also showed an increase. Connectivity between prefrontal cortex (dlPFC and vmPFC) and subcortical regions (caudate, amygdala) decreased across development. Moreover, higher testosterone predicted average negative mood at the next time point, but not vice versa. Further, stronger vmPFC-amygdala functional connectivity predicted decreases in mood variability. Here, we show that brain connectivity during development is an important within-person biological mechanism of the development of mood in adolescents. PRACTITIONER POINTS: Mood variability peaks in adolescence. Within-person changes in testosterone predict within-person changes in mood. Within-person changes in vmPFC-amygdala connectivity predict within-person changes in mood variability.

Puberty in girls with Prader-Willi syndrome: cohort evaluation and clinical recommendations in a Latin American tertiary center.

Introduction: Prader-Willi syndrome (PWS) is a genetic disorder characterized by hypothalamic-pituitary deficiencies including hypogonadism. In girls with PWS, hypogonadism can present early in childhood, leading to genital hypoplasia, delayed puberty, incomplete pubertal development, and infertility. In contrast, girls can present with premature activation of the adrenal axis leading to early pubarche and advanced bone age. We aim to evaluate the progression of puberty and adrenarche signals in girls with PWS. Methodology: A longitudinal retrospective cohort study included girls with PWS followed at a Pediatric Endocrinology Outpatient Clinic in a Tertiary University Hospital in Sao Paulo, Brazil from 2002 to 2022. Data collected via chart review included clinical information on birth history, breast and pubic hair Tanner stages, presence of genital hypoplasia, age at menarche, regularity of menstrual cycles, body mass index (BMI) z-score, final height, age of initiation of estrogen replacement and growth hormone replacement, as well as results for PWS genetic subtype; biochemical investigation (LH, FSH, estradiol, DHEA-S); radiographic bone age and pelvic ultrasound. Results: A total of 69 girls were included in the study and the mean age of puberty onset was 10.2 years in those who started puberty after the age of 8 years. Breast Tanner stage IV was reached by 29.1% girls at a mean age of 14.9 years. Spontaneous menarche was present in 13.8% and only one patient had regular menstrual cycles. Early adrenarche was seen in 40.4% of cases. Conclusion: Our study demonstrated in a large sample that girls with PWS often present with delayed onset of puberty despite frequent premature adrenarche. Based on our results, we suggest an estrogen replacement protocol for girls with PWS to be started at the chronological age or bone age of 12-13 years, taking into consideration the uterus size. Further prospective studies are needed.

Alkylating agents-induced gonadotoxicity in prepubertal males: Insights on the clinical and preclinical front.

Rising cure rates in pediatric cancer patients warrants an increased attention toward the long-term consequences of the diagnosis and treatment in survivors. Chemotherapeutic agents can be gonadotoxic, rendering them at risk for infertility post-survival. While semen cryopreservation is an option that can be provided for most (post)pubertal boys before treatment, this is unfortunately not an option prepubertal in age, simply due to the lack of spermatogenesis. Over the last couple of years, studies have thus focused on better understanding the testis niche in response to various chemotherapeutic agents that are commonly administered and their direct and indirect impact on the germ cell populations. These are generally compounds that have a high risk of infertility and have been classified into risk categories in curated fertility guidelines. However, with it comes the lack of evidence and the challenge of using informative models and conditions most reflective of the physiological scenario, in short, the appropriate study designs for clinically relevant outcomes. Besides, the exact mechanism(s) of action for many of these "risk" compounds as well as other agents is unclear. Understanding their behavior and effect on the testis niche will pave the way for incorporating new strategies to ultimately combat infertility. Of the various drug classes, alkylating agents pose the highest risk of gonadotoxicity as per previously established studies as well as risk stratification guidelines. Therefore, this review will summarize the findings in the field of male fertility concerning gonadotoxicity of akylating agents as a result of chemotherapy exposure.

Reward positivity moderates the association between pubertal status and social anxiety symptoms in nine-to-12-year-old youths.

The transition to adolescence is characterized by rapid development of puberty, reward processing, and internalizing psychopathology (i.e., depression and anxiety). More advanced pubertal status and altered reward processing are both known to be associated with elevated internalizing symptoms. However, it was unclear to what extent pubertal status and reward processing interacted with each other in predicting internalizing psychopathology. We examined how the puberty-psychopathology association was moderated by the reward processing indexed by ERPs, including the reward positivity (RewP) and the late positive potential (LPP). A-hundred-and-fifteen nine-to-12-year-old typically developing youths (66 girls; Mean age/SD =10.98/1.18 years) reported their pubertal status and symptoms of depression and social anxiety and completed an EEG Doors task that assessed monetary reward feedback processing. A principal component analysis of the ERP data identified a RewP, an anterior LPP, and a posterior LPP, elicited by the win and loss feedback of the task. The puberty-social anxiety relationship was moderated by the RewP, an identified neural marker of reward sensitivity. Specifically, more advanced puberty was associated with heightened social anxiety symptoms in the presence of a larger, but not smaller, RewP. We did not observe any moderating effect of the LPPs. Our study provided novel evidence that a hypersensitivity toward the reward stimuli (indexed by an enlarged RewP) further exacerbated the risks associated with more advanced pubertal status for social anxiety.

Cross-sectional and longitudinal analysis of bone age maturation during peri-pubertal growth in children with type I, III and IV osteogenesis imperfecta.

Osteogenesis imperfecta (OI)is a rare genetically heterogeneous disorder caused by changes in the expression or processing of type I collagen. Clinical manifestations include bone fragility, decreased linear growth, and skeletal deformities that vary in severity. In typically growing children, skeletal maturation proceeds in a predictable pattern of changes in the size, shape, and mineralization on the hand and wrist bones that can be followed radiographically known at the bone age. Assessment of bone age can be clinically used to assess time remaining for linear growth, and the onset and duration of puberty, both of which can be useful in determining the timing of some surgeries or the interpretation of other imaging modalities such as bone densitometry. Additionally, deviations in the expected maturation process of the bone age may prompt or assist in the work up of a significant delay or advancement in a child's growth pattern. The primary aim of our study was to determine whether the bone age in children with a skeletal disorder such as OI follow the same pattern and rate of bone maturation compared to a control population. Using participants from the Natural History Study of the Brittle Bone Disorders Consortium, we analyzed 159 left hand and wrist radiographs (bone age) for a cross-sectional analysis and 55 bone ages repeated at approximately 24 months for a longitudinal analysis of skeletal maturation. Bone ages were read by a pediatric endocrinologist and by an automated analysis using a program called BoneXpert. Our results demonstrated that in children with mild-to-moderate OI (types I and IV), the skeletal maturation is comparable to chronological age-mated controls. For those with more severe forms of OI (type III), there is a delayed pattern of skeletal maturation of less than a year (10.5 months CI 5.1-16) P = 0.0012) at baseline and a delayed rate of maturation over the two-year follow up compared to type I (P = 0.06) and type III (P = 0.02). However, despite these parameters being statistically different, they may not be clinically significant. We conclude the bone age, with careful interpretation, can be used in the OI population in a way that is similar to the general pediatric population.