Pubertal Hormone Levels Research Articles

Basal gonadotropin levels combine with pelvic ultrasound and pituitary volume: a machine learning diagnostic model of idiopathic central precocious puberty

ObjectiveThe current diagnosis of central precocious puberty (CPP) relies on the gonadotropin-releasing hormone analogue (GnRHa) stimulation test, which requires multiple invasive blood sampling procedures. The aim of this study was to construct machine learning models incorporating basal pubertal hormone levels, pituitary magnetic resonance imaging (MRI), and pelvic ultrasound parameters to predict the response of precocious girls to GnRHa stimulation test.MethodsThis retrospective study included 455 girls diagnosed with precocious puberty who underwent transabdominal pelvic ultrasound, brain MRI examinations and GnRHa stimulation testing were retrospectively reviewed. They were randomly assigned to the training or internal validation set in an 8:2 ratio. Four machine learning classifiers were developed to identify girls with CPP, including logistic regression, random forest, light gradient boosting (LightGBM), and eXtreme gradient boosting (XGBoost). The accuracy, sensitivity, specificity, positive predictive value, negative predictive value, area under receiver operating characteristic (AUC) and F1 score of the models were measured.ResultsThe participates were divided into an idiopathic CPP group (n = 263) and a non-CPP group (n = 192). All machine learning classifiers used achieved good performance in distinguishing CPP group and non-CPP group, with the area under the curve (AUC) ranging from 0.72 to 0.81 in validation set. XGBoost had the highest diagnostic efficacy, with sensitivity of 0.81, specificity of 0.72, and F1 score of 0.80. Basal pubertal hormone levels (including luteinizing hormone, follicle-stimulating hormone, and estradiol), averaged ovarian volume, and several uterine parameters were predictors in the model.ConclusionThe machine learning prediction model we developed has good efficacy for predicting response to GnRHa stimulation tests which could help in the diagnosis of CPP.

The development of sensorimotor cortical oscillations is mediated by pubertal testosterone

Puberty is a period of substantial hormonal fluctuations, and pubertal hormones can modulate structural and functional changes in the developing brain. Many previous studies have characterized the neural oscillatory responses serving movement, which include a beta event-related desynchronization (ERD) preceding movement onset, gamma and theta responses coinciding with movement execution, and a post-movement beta-rebound (PMBR) response following movement offset. While a few studies have investigated the developmental trajectories of these neural oscillations serving motor control, the impact of pubertal hormone levels on the maturation of these dynamics has not yet been examined. Since the timing and tempo of puberty varies greatly between individuals, pubertal hormones may uniquely impact the maturation of motor cortical oscillations distinct from other developmental metrics, such as age. In the current study we quantified these oscillations using magnetoencephalography (MEG) and utilized chronological age and measures of endogenous testosterone as indices of development during the transition from childhood to adolescence in 69 youths. Mediation analyses revealed complex maturation patterns for the beta ERD, in which testosterone predicted both spontaneous baseline and ERD power through direct and indirect effects. Age, but not pubertal hormones, predicted motor-related theta, and no relationships between oscillatory responses and developmental metrics were found for gamma or PMBR responses. These findings provide novel insight into how pubertal hormones affect motor-related oscillations, and highlight the continued development of motor cortical dynamics throughout the pubertal period.

Reproductive Markers of Testicular Function and Size During Puberty in Boys With and Without a History of Cryptorchidism.

Longitudinal data on levels of hypothalamic-pituitary-gonadal axis hormones and insulin-like growth factor I (IGF-I) during puberty in boys with a history of cryptorchidism are largely missing. We aimed to compare pubertal hormone levels between boys with a history of congenital cryptorchidism who experienced spontaneous testicular descent or underwent orchiopexy and boys without a history of cryptorchidism. This was a nested case-control study within a population-based birth cohort, with a prospective, longitudinal pubertal follow-up every 6 months (2005 to 2019). Participants were 109 Finnish boys, including boys with a history of unilateral cryptorchidism who underwent orchiopexy (n = 15), unilateral cryptorchidism who had spontaneous testicular descent (n = 15), bilateral cryptorchidism who underwent orchiopexy (n = 9), bilateral cryptorchidism who had spontaneous testicular descent (n = 7), and controls (n = 63). Serum reproductive hormone levels and testicular volumes were measured. From around onset of puberty, boys with bilateral cryptorchidism who underwent orchiopexy had significantly higher follicle-stimulating hormone (FSH) and lower inhibin B levels than controls. Boys with unilateral cryptorchidism who underwent orchiopexy had significantly higher FSH than controls, whereas inhibin B levels were similar. Testosterone, luteinizing hormone, insulin-like factor 3, and IGF-I were generally similar between groups. Testicular volume of boys with unilateral or bilateral cryptorchidism who underwent orchiopexy was smaller than that of the controls from 1 year after pubertal onset (P < 0.05). Cryptorchid boys, particularly those with bilateral cryptorchidism who underwent orchiopexy, had altered levels of serum biomarkers of Sertoli cells and germ cells and smaller testicular volumes compared with controls.

Altered Brain Structure and Functional Connectivity Associated with Pubertal Hormones in Girls with Precocious Puberty

Pubertal hormones play an important role in brain and psychosocial development. However, the role of abnormal HPG axis states in altering brain function and structure remains unclear. The present study is aimed at determining whether there were significant differences in gray matter volume (GMV) and resting state (RS) functional connectivity (FC) patterns in girls with idiopathic central precocious puberty (CPP) and peripheral precocious puberty (PPP). We further explored the correlation between these differences and serum pubertal hormone levels. To assess this, we recruited 29 idiopathic CPP girls and 38 age-matched PPP girls. A gonadotropin-releasing hormone (GnRH) stimulation test was performed, and pubertal hormone levels (including luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), prolactin, and cortisol) were assessed. All subjects underwent multimodal magnetic resonance imaging of brain structure and function. Voxel-based morphometry (VBM) analysis was paired with seed-to-voxel whole-brain RS-FC analysis to calculate the GMV and RS-FC in idiopathic CPP and PPP girls. Correlation analyses were used to assess the effects of pubertal hormones on brain regions with structural and functional differences between the groups. We found that girls with CPP exhibited decreased GMV in the left insula and left fusiform gyrus, while connectivity between the left and right insula and the right middle frontal gyrus (MFG), as well as the left fusiform gyrus and right amygdala, was reduced in girls with CPP. Furthermore, the GMV of the left insula and peak FSH levels were negatively correlated while higher basal and peak E2 levels were associated with increased bilateral insula RS-FC. These findings suggest that premature activation of the HPG axis and pubertal hormone fluctuations alter brain structure and function involved in the cognitive and emotional process in early childhood. These findings provide vital insights into the early pathophysiology of idiopathic CPP.

Adolescents' pubertal development: Links between testosterone, estradiol, and neural reward processing

• Adolescent pubertal hormone levels were related to neural activation in an fMRI reward task. • Heightened testosterone levels were associated with blunted dlPFC activation. • Heightened estradiol was related to lower NAcc-prefrontal region connectivity.

Stress physiology and memory for emotional information: Moderation by individual differences in pubertal hormones.

In contrast to a large body of work concerning the effects of physiological stress reactivity on children's socioemotional functioning, far less attention has been devoted to understanding the effects of such reactivity on cognitive, including mnemonic, functioning. How well children learn and remember information under stress has implications for a range of educational, clinical, and legal outcomes. We evaluated 8-14 year olds' (N = 94, 50 female) memory for negative, neutral, and positive images. Youth had seen the images a week previously as a part of a laboratory stress task. At encoding and retrieval, and in between, youth provided saliva samples that were later assayed for cortisol, salivary α amylase (sAA), testosterone, and dehydroepiandrosterone (DHEA). Overall, higher cortisol reactivity to the lab task predicted enhanced memory for emotional but not neutral images. However, cortisol further interacted with pubertal hormones (testosterone and DHEA) to predict memory. Among girls with lower pubertal hormone levels, greater cortisol reactivity was associated with enhanced memory for negative information, whereas among boys with higher pubertal hormone levels, cortisol reactivity was associated with enhanced memory for positive information. sAA, was unrelated to memory. Overall, our findings reveal that individual differences in hormone levels associated with pubertal development have implications for our understanding of how stress-responsive biological systems directly and interactively influence cognitive outcomes. (PsycINFO Database Record

Modelling 3D craniofacial growth trajectories for population comparison and classification illustrated using sex-differences

Many disorders present with characteristic abnormalities of the craniofacial complex. Precise descriptions of how and when these abnormalities emerge and change during childhood and adolescence can inform our understanding of their underlying pathology and facilitate diagnosis from craniofacial shape. In this paper we develop a framework for analysing how anatomical differences between populations emerge and change over time, and for binary group classification that adapts to the age of each participant. As a proxy for a disease-control comparison we use a database of 3D photographs of normally developing boys and girls to examine emerging sex-differences. Essentially we define 3D craniofacial ‘growth curves’ for each sex. Differences in the forehead, upper lip, chin and nose emerge primarily from different growth rates between the groups, whereas differences in the buccal region involve different growth directions. Differences in the forehead, buccal region and chin are evident before puberty, challenging the view that sex differences result from pubertal hormone levels. Classification accuracy was best for older children. This paper represents a significant methodological advance for the study of facial differences between growing populations and comprehensively describes developing craniofacial sex differences.

Bone Accrual in Males with Autism Spectrum Disorder

To test the hypothesis that bone accrual over a 4-year period is reduced in boys with autism spectrum disorder (ASD) compared with typically developing controls. Twenty-five boys with ASD and 24 controls were assessed for bone outcomes. Fourteen boys with ASD and 11 controls were assessed both at baseline and after 4 years. The mean subject age was 11.0 ± 1.6 years at study initiation and 14.9 ± 1.6 years at follow-up. Bone mineral density (BMD) was measured at the spine, hip, and whole body using dual-energy X-ray absorptiometry and normalized for age, race, and sex (BMD z-scores). Height adjustments were performed as well. We assessed medical history, physical activity using questionnaires, vitamin D and calcium intake using food records, and serum calcium, phosphorus, 25(OH)-vitamin D, and pubertal hormone levels. Boys with ASD had lower spine, hip, and whole body BMD z-scores compared with controls. In those subjects assessed both at baseline and after 4 years, bone accrual rates did not differ between the 2 groups; however, spine and hip BMD z-scores remained lower in the boys with ASD than in controls at follow-up. Notably, the ASD group was less physically active at both time points. Although pubertal bone accrual was similar to that in controls, BMD in children with ASD remained low over a 4-year follow-up period, suggesting that low BMD is a consequence of prepubertal factors, such as low physical activity. Studies are needed to investigate the causes and consequences of decreased BMD, to assess BMD in females and adults with ASD, and to evaluate therapeutic interventions.

Comparison of Detection of Normal Puberty in Girls by a Hormonal Sleep Test and a Gonadotropin-Releasing Hormone Agonist Test

The magnitude of sleep-related gonadotropin rise required to activate pubertal feminization is not established. The objective of the study was to determine the normal relationship of pubertal hormone responses to sleep and to GnRH agonist (GnRHag) challenge across the female pubertal transition. This was a prospective study in a General Clinical Research Center. Sixty-two healthy 6- to 13-year-old volunteer girls participated in the study. Interventions included overnight blood sampling followed by GnRHag (leuprolide acetate) injection. The primary outcome variables included LH, FSH, and estradiol. LH levels rose steadily during sleep and after GnRHag throughout the prepubertal years. The LH response to sleep and GnRHag correlated well across groups (eg, r = 0.807, peak vs 4 h post-GnRHag value); however, this correlation was less robust than in boys (r = 0.964, P < .01). Sleep peak LH of 1.3 U/L or greater had 85% sensitivity and 2.1 U/L or greater 96% specificity for detecting puberty (thelarche). The LH 1-hour post-GnRHag value of 3.2 U/L or greater had 95% sensitivity and 5.5 U/L or greater 96% specificity for detecting puberty. Girls entered puberty at lower LH levels than boys. FSH levels rose day and night during the prepubertal years to reach 1.0 U/L or greater during puberty but discriminated puberty poorly. Estradiol of 34 pg/mL or greater at 20-24 hours after GnRHag was 95% sensitive and 60 pg/mL or greater was 95% specific for puberty. Thirty-six percent of overweight early pubertal girls had meager hormonal evidence of puberty. These data suggest that sleep-related pubertal hormone levels critical for puberty are normally reflected in the responses to GnRHag testing across the normal female pubertal transition. Inconsistencies between clinical and hormonal staging may arise from peripubertal cyclicity of neuroendocrine function and from excess adiposity.

Longitudinal Study of Hormonal and Physical Development in Young Twins

Information on the correlation of normative reproductive hormone levels with physical development (Tanner stages) during puberty and on the influences of genes and environment on variation in these hormones and Tanner stages is limited. One hundred twelve healthy 9-year-old twin pairs (n = 224) took part in a longitudinal study, of which 89 pairs participated again at age 12 years (n = 178). Morning urinary LH, FSH, estradiol, and salivary testosterone levels, determined by competitive immunoassays, were measured. Tanner stages were determined through physical examination. Over the 3-year interval, all hormone levels showed a 2- to 9-fold increase. LH and FSH at age 9 years predicted sex-specific Tanner stages at age 12 years in both boys and girls. Most of the associations between hormone levels at age 9 years and physical development at 12 years were explained by genetic influences. FSH in 9-year-old boys correlated with all hormone levels and Tanner stages at age 12 years. Moderate to high heritability estimates were found for hormone levels at both ages and in both sexes. In girls a shift from environmental (age 9 years) to genetic influences (age 12 years) was found for estradiol and pubic hair development, and for breast development a shift in the opposite direction was seen. During development LH and FSH (and testosterone in boys) levels predict secondary sexual characteristics in boys and girls 3 years later. These correlations are largely due to genes that are involved in both early pubertal hormone levels and subsequent physical development.

Comparison of Detection of Normal Puberty in Boys by a Hormonal Sleep Test and a Gonadotropin-Releasing Hormone Agonist Test

The magnitude of sleep-related gonadotropin rise required to activate pubertal gonadal function is not established. Our objective was to determine the normal relationship between sleep-related pubertal hormone levels and pituitary-testicular responsiveness to a GnRH agonist (GnRHag) test across the pubertal transition. DESIGN/SETTING AND PARTICIPANTS: We conducted a prospective study in a General Clinical Research Center with healthy 9- to 15-yr-old volunteer boys. INTERVENTIONS included overnight blood sampling followed by leuprolide acetate injection (10 μg/kg). LH, FSH, and testosterone levels were evaluated. LH levels during sleep and post-GnRHag rose steadily during the late prepubertal years. Sleep peak LH correlated highly with the LH response to GnRHag across groups (r = 0.913). A sleep peak LH level of at least 3.7 U/liter predicted pubertal testicular activation with 100% accuracy. LH of at least 14.8 and at least 19.0 U/liter 4 h after GnRHag, respectively, predicted puberty with 100% sensitivity/94% specificity and 100% specificity/94% sensitivity. Overweight pubertal boys had transiently prolonged responses to GnRHag. FSH rose during both waking and sleeping hours during the prepubertal years, and all pubertal boys had an FSH level of at least 0.9 U/liter awake and at least 1.2 U/liter asleep. Sleep LH was more closely related than FSH to testicular size. These data suggest that a critical LH level during sleep (≥3.7 U/liter) heralds the onset of pubertal virilization and that this level is predictable by LH of at least 14.8-19 U/liter 4 h after GnRHag. These data also suggest that LH stimulation of testicular androgen production plays a role in stimulating testicular tubule growth once a critical level of FSH is achieved.

Age, environmental factors and prostatic cancer

Although prostatic cancer is evident late in life, pathological evidence suggests this disease is initiated earlier in life. As prostatic cancer is an endocrine associated disease and as adult hormone profiles are established during puberty, it was of interest whether difference in pubertal hormone levels occurred in pupulations at low or high risk for prostatic cancer. Accordingly we have investigated the hormone profiles in rural Black South African and urban white boys during puberty. It has been suggested that the timing of puberty is modified by environmental factors and that there is a concomitant control of gonadotrophin release and food intake by CNS-peptide hormones. It is therefore postulated that dietary factors during puberty modify the gut-CNS peptide hormones which in turn control the hypothalamic-pituitarytesticular axis. Distinct difference in plasma androgen and gonadotrophins between the two races are in part concordant with a modification of CNS-peptide hormones by environmental factors during puberty.