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Aims: We studied whether first morning voided (FMV) urinary gonadotropin measurements could be used as a noninvasive alternative to the GnRH test in the assessment of the hypothalamic-pituitary-gonadal function in children., Methods: In a single-center study, we compared FMV urinary gonadotropin concentrations with basal and GnRH-stimulated serum gonadotropin levels in 274 children and adolescents (78 girls, 196 boys) aged 5-17 years referred for growth and pubertal disorders. The concordance between FMV urinary gonadotropin concentrations and GnRH test results was assessed., Results: FMV urinary LH (U-LH), urinary FSH (U-FSH) and their ratios correlated well with the corresponding basal and GnRH-stimulated serum parameters (r ≥ 0.66, p < 0.001). Receiver operating characteristic curve analyses using urinary and serum LH and FSH concentrations showed that FMV U-LH and U-LH/U-FSH performed equally well as the GnRH test in the differentiation of early puberty (Tanner stage 2) from prepuberty (Tanner stage 1) (area under the curve 0.768-0.890 vs. 0.712-0.858). FMV U-LH and U-LH/U-FSH performed equally well as basal serum LH in predicting a pubertal GnRH test result (area under the curve 0.90-0.93)., Conclusion: FMV U-LH determination can be used for the evaluation of pubertal development and its disorders, reducing the need for invasive GnRH stimulation tests., (© 2016 S. Karger AG, Basel.)

Background/aim: The goal of estrogen replacement therapy (ERT) in girls with hypogonadism is to achieve the endocrine milieu similar to natural puberty, where transdermal administration is the most physiological route. The aim of the study was to evaluate guidelines for the induction of puberty with transdermal estradiol (E2) patches in a large outpatient setting., Methods: In a retrospective study, serum E2 levels from 18 clinics were analyzed at the Göteborg Pediatric Growth Research Center laboratory, as part of the initiation of ERT in girls with hypogonadism. Exclusion criteria were pubertas tarda and pubertal arrest. Eighty-eight observations (50 with Turner syndrome, TS) were included. Serum E2 levels were determined by extraction + radioimmunoassay (detection limit 4 pmol/l) and analyzed in relation to the dose of Evorel(®) (25 µg/24 h, containing 1.60 mg estradiol hemihydrate; Janssen-Cilag Pharmaceutica N.V., Beerse, Belgium)., Results: There was a linear relationship between serum E2 and the weight-based dose, with r = 0.56, p < 0.0001 for all observations and r = 0.59, p < 0.0001 for the TS study group. Linear regression analysis for doses of 0.05-0.07 µg/kg resulted in serum levels of 17-23 pmol/l (TS 17-24 pmol/l) and doses of 0.08-0.12 µg/kg in 26-39 pmol/l (TS 27-39 pmol/l)., Conclusions: For the initiation of ERT with nocturnally administered E2 patches, we recommend reduced starting doses of 0.05-0.07 µg/kg, with the goal of mimicking E2 levels during gonadarche. In older girls, when breast development is of high priority, the starting dose can still be 0.08-0.12 µg/kg.

Background/aims: To study serum testosterone and estradiol in healthy boys in relation to growth during puberty up to peak height velocity (PHV)., Methods: Growth velocity was analyzed through testosterone (n = 41) and 17β-estradiol (n = 37) 24-hour profiles in a dose-response model. Participants were 26 healthy boys admitted for short or tall stature or participating as healthy volunteers at the Queen Silvia Children's Hospital. Other inclusion criteria included the following: gestational age 37-42 weeks, birth weight and length >-2 standard deviation score (SDS) and prepubertal height and weight within ± 3 SDS. Testosterone was measured using a modified radioimmunoassay (RIA) with a detection limit of 0.03 nmol/l. Estradiol was determined using an ultrasensitive extraction RIA with a detection limit 4 pmol/l. A sixth-grade polynomial was fitted to each child's growth data, giving growth velocity and age at PHV., Results: Growth velocity increased by 50% from prepubertal growth to PHV at a morning testosterone level of 3.1 nmol/l (95% confidence interval 2.4-4.2), EC50. The corresponding EC50 of 17β-estradiol was 6.5 pmol/l (3.2-13). Boys approaching PHV (<4% remaining) had morning testosterone levels >10 nmol/l and 17β-estradiol >9 pmol/l., Conclusion: Observed early puberty/initial mid puberty morning testosterone levels of 2.4-4.2 nmol/l are associated with a 50% increase in growth velocity from prepubertal growth to PHV in healthy boys., (Copyright © 2013 S. Karger AG, Basel.)

Aim: The objective of this study was to determine estradiol levels and assess their relationship to pubertal growth in girls., Methods: Thirty-seven 24-hour profiles of serum 17β-estradiol were retrospectively analyzed in relation to growth in 27 healthy girls admitted for short/tall stature (n = 20) or recruited as healthy volunteers at Göteborg Pediatric Growth Research Center (GP-GRC)., Inclusion Criteria: Birth weight and length above -2 SDS, gestational age 37-42 weeks, prepubertal height and weight within ± SDS and normal growth hormone secretion. Serum estradiol was determined by a validated ultrasensitive extraction radioimmunoassay (detection limit 4 pmol/l). A sixth-grade polynomial was fitted to each girl's growth data. Growth velocity and age at peak height velocity (PHV) was calculated., Results: A dose-response model was used to find the morning 17β-estradiol level at which half of the maximal pubertal growth up to PHV had occurred, EC(50), which was 20 pmol/l with a 95% confidence interval of 13-31. When 17β-estradiol exceeds early pubertal levels (Tanner breast stage 2, 10-51 pmol/l), less than 25% of the potential pubertal growth velocity up to PHV remains., Conclusions: Morning 17β-estradiol in the low early pubertal range (13-31 pmol/l) is associated with increasing growth velocity., (Copyright © 2012 S. Karger AG, Basel.)

Objective: To investigate the impact of pubertal timing and childhood body mass index (BMI), both within normal range, on adult anthropometrics., Study Design: Detailed growth charts were retrieved for the men participating in the population-based Gothenburg Osteoporosis and Obesity Determinants study. Age at peak height velocity and childhood BMI were calculated (n = 527), and anthropometric measurements were performed., Results: Analysis of variance analysis of tertiles according to age at peak height velocity demonstrated that the early peak height velocity tertile had a lower adult height (180.9 ± 6.8 cm) compared with the middle tertile group (182.7 ± 6.9 cm, P < .05), and this difference was attributable to shorter leg length. No difference was seen for sitting height. In contrast, analysis of tertiles according to childhood BMI demonstrated low sitting height in the low BMI tertile (93.7 ± 3.3 cm for low, 94.6 ± 3.3, for middle, and 94.8 ± 3.3 cm for high childhood BMI tertiles, P < .05 and P < .01, respectively), but childhood BMI did not affect adult height and leg length., Conclusion: We demonstrate that subjects with early pubertal timing have reduced adult height and leg length, and subjects with low childhood BMI have reduced adult sitting height. Thus childhood body composition and pubertal timing have different impact on trunk growth and growth of long bones., (Copyright © 2011 Mosby, Inc. All rights reserved.)

The role of puberty and normal variations in pubertal timing for the development of obesity in men is unclear. The aim of the current study was to investigate the impact of pubertal timing and prepubertal BMI (kg/m(2)) for young adult BMI and fat mass distribution. Detailed growth charts from birth to age 18-20 years were retrieved for the men participating in the population-based Gothenburg Osteoporosis and Obesity Determinants study. Age at peak height velocity (PHV) and BMI at age 10 years were estimated for 579 subjects, and PHV was used as an assessment of pubertal timing. The fat mass characterization and distribution were analyzed using dual X-ray absorptiometry and peripheral as well as abdominal computed tomography at age 18.9 +/- 0.5 years. We demonstrate that age at PHV is an independent negative predictor of young adult BMI and whole-body fat mass. Interestingly, age at PHV is an independent negative predictor of central, but not peripheral, fat mass. In contrast, BMI at 10 years of age predicts both central and peripheral subcutaneous fat mass. In conclusion, we demonstrate that early pubertal onset specifically predicts a central fat mass distribution, while a predominantly subcutaneous obese phenotype is strongly predicted by a high prepubertal BMI.

Unlabelled: The importance of pubertal timing for adult BMD in males was studied through association of pubertal timing with young adult bone phenotype. Pubertal timing was found to predict both cortical and trabecular volumetric BMD and previous fractures in young adult men. Thus, late puberty is a risk factor for low BMD and previous fractures in young adult men., Introduction: Peak bone mass (PBM), achieved during puberty, is a determinant of the risk for osteoporosis and future fractures. The role of variations within the normal range in pubertal timing for fractures during pubertal development and for adult bone mass in men is unknown., Materials and Methods: The aim of this study was to investigate the importance of pubertal timing for adult BMD and for fractures before achievement of PBM in men. The population-based Gothenburg Osteoporosis and Obesity Determinants (GOOD) study is a well-characterized cohort of young adult Swedish males 18-20 years of age. Detailed growth charts from birth to 18-20 years of age were retrieved for 642 men participating in the GOOD study. Age at peak height velocity (PHV) was estimated and used as an assessment of pubertal timing. The skeletal phenotype was analyzed at young adult age using DXA and pQCT and previous fractures were assessed by questionnaires., Results: Age at PHV was a negative independent predictor of both adult cortical and trabecular volumetric BMD and of total body and radius areal BMD. Moreover, age at PHV was associated with previous fractures in a logistic regression analysis. The OR for cortical osteopenia was 2.49 (95% CI, 1.91-3.24; p < 0.001) and for previous upper limb fractures was 1.35 (95% CI, 1.04-1.75; p < 0.05) per year increment in age at PHV., Conclusions: Age at PHV is a negative independent predictor of BMD and a positive predictor of previous fractures in young adult men. Longitudinal studies to determine if pubertal timing also predicts BMD and fractures in elderly men are required.

Objective: To establish levels for comparison for 24-h total and free serum testosterone in prepubertal boys and throughout pubertal development., Design: The study subjects were 55 healthy boys, aged 5.0-18.6 years, who underwent serial sampling one or more times during their pubertal development., Methods: Testicular volumes were determined by orchidometer. Serum testosterone was measured by a modified RIA (detection limit, 0.03 nmol/l). Free testosterone was calculated (calc-FT) using a formula derived from the law of mass action., Results: Significant increases in testosterone and calc-FT concentrations in boys were found between testis volumes of 1 ml to 2 ml, 2 ml to 3 ml, 6 ml to 8 ml, and 10 ml to 15 ml. No differences were found between testis volumes of 3, 4, 5 and 6 ml neither were there differences between 8 and 10 ml, or between 15, 20 and 25 ml. Boys who had reached their final height had higher calc-FT values than boys who had the same pubertal development but had not reached their final height. Based on the results, puberty was classified into six stages: pre1 (testis, 1 ml), pre2 (testis, 2 ml), early (testis, 3-6 ml), mid (testis, 8-12 ml), late1 (testis,15-25 ml, not reached final height) and late2 (testis, 15-25 ml, reached final height). Serum testosterone was secreted with a diurnal variation in prepuberty and during puberty. The increase of testosterone in the morning hours started earlier in pubertal than in pre-pubertal boys. The most pronounced diurnal rhythm was found in early and in mid puberty., Conclusion: Using a sensitive method, and a pubertal reclassification, we have established levels for comparison of testosterone and calc-FT in prepubertal and pubertal boys. The existence of data for comparison forms the basis for future studies on pubertal disorders.

Context: The use of testosterone enanthate (TE), 50-75 mg intramuscularly (i.m.)/month, for the treatment of boys with delayed puberty or slow progression to induce puberty is the standard of care (SoC) in Sweden. This treatment is empirical and has not been scientifically evaluated. Replacement therapy in hypogonadal boys/young men in Sweden after induction is mainly performed with testosterone undecanoate (TU), 1,000 mg/3 months. TE is only available on license. TE was deregistered in Sweden in 2006. Therefore, this study was initiated to compare the two products. Objective: To clinically evaluate pubertal progression with six injections of TE, 75 mg i.m./month (1/3-1/5 of adult dose), compared with two injections of TU, 250 mg i.m./3 months (1/4 of adult dose). Trial design: In the Pubertal Replacement in Boys Study (PRIBS), boys aged 14-16 years in West Sweden with pubertal delay were randomized in a parallel study to TE or TU for pubertal progression. Inclusion criteria were morning testosterone levels of 0.5-3 nmol/L and testicular volume =6 ml. Between June 2014 and Nov 2019, 27 boys were included. Methods: The primary outcome was testicular enlargement =8 ml after 12 months. TU treatment was considered clinically similar if the number of boys with testicular enlargement =8ml was 80%-125% of the number of boys with TE. Fisher's exact chi-square test was used for this analysis. Results: Both treatments were well tolerated. Twelve of 14 (86%) TU-treated boys reached the primary outcome and 12/12 in the TE group. Fisher's exact chisquare testing indicated a one-sided p-value of 0.28 (the two-sided p-value was 0.483). The TU treatment was considered not clinically different from SoC. A post-hoc study showed 25% power. Therefore, no evidence-based conclusion can be drawn from the results even if the clinical data support a similar effect of the treatments. Conclusion: The present small-scale study supports that both TE and TU had similar effects in terms of pubertal progression. [ABSTRACT FROM AUTHOR]

Interpretations: Our findings suggest that if oestrogen action is inhibited in growing adolescents, adult height will increase. This finding provides a rationale for studies that aim to delay bone maturation in several growth disorders. [ABSTRACT FROM AUTHOR]