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Effects of high dose oestrogen and testosterone treatment in adolescents upon trabecular and compact bone measured by 125I computed tomography. A preliminary study

Gerhard Ulrich Exner, Andrea Prader, Urs Elsasser, and Max Anliker

Abstract.

125I Computed Tomography (CT) allows for the selective determination of trabecular and compact bone mineral parameters in the radius. Using this technique the effects of high dose oestrogen treatment in 11 tall girls, and of high dose testosterone treatment in 5 tall boys were monitored. In both groups trabecular bone density (TBD) increased steadily during treatment at a rate of about 1% per month. Also in both groups the compact bone mineral increased steadily. These results are compared with those from a cross sectional study on 49 normal children and 36 normal adults, in whom TBD was found to be independent of age and sex, so that the increases in TBD in both treatment groups can be attributed directly to the influence of the sex hormones. Since the compact bone mineral is higher in adults than in children it cannot yet be decided whether the increases seen in the treated patients are related to the sex hormone treatment, or reflect only the normal development of the bone during adolescence.

Open access

An optimal growth pattern during pregnancy and early childhood associates with better fertility in men

Johanna Laru, Marja Ojaniemi, Stephen Franks, Marjo-Riitta Järvelin, Elisa Korhonen, Terhi T Piltonen, Sylvain Sebert, Juha S Tapanainen, and Laure Morin-Papunen

Objective

This study aimed to evaluate the association between birth weight (BW), childhood and adolescent BMI, with reproductive capacity in men.

Design

A prospective, population-based cohort study (Northern Finland birth cohort 1966).

Methods

Around 6196 men born in 1966 were followed from birth to age 50 years. Weight and height were measured repeatedly by professionals. Reproductive capacity (infertility assessment, male factor infertility and infertility treatment by age 46 years) was evaluated by questionnaires at ages 31 and 46 years. The number of children by the age of 50 years was recovered from registers. After excluding the men who reported never having attempted to have children or not answering the question at age 31 or 46 years (n = 2041), 4128 men were included in the final study population. Results were adjusted for BW, BW for gestational age (GA), mother’s smoking status, marital status, educational level and smoking status.

Results

Being small for GA (10.5% vs 8.2%, P = 0.012) or having a lower BW (3495 g vs 3548 g, P = 0.003) were associated with childlessness. The association was however no longer significant after adjusting for marital status. Being underweight in early childhood was associated with an increased risk of infertility assessment (adjusted, aOR: 2.04(1.07–3.81)) and childlessness (aOR: 1.47(1.01–2.17)) compared to the normal weight group. Conversely, overweight or obesity in early childhood was associated with a decreased risk of infertility assessment (aOR: 0.60 (0.41–0.87)), treatment (aOR: 0.42 (0.25–0.70)) and male factor infertility (aOR: 0.45 (0.21–0.97)). BMI in mid-childhood or puberty had no association with infertility or childlessness.

Conclusion

In boys, an optimal growth trajectory during pregnancy and early childhood seems to be very important for life-long fertility.

Free access

Distribution of the homeostasis model assessment of insulin resistance in Mexican children and adolescents

Celia Aradillas-García, Martha Rodríguez-Morán, María Eugenia Garay-Sevilla, Juan Manuel Malacara, Ramón Alberto Rascon-Pacheco, and Fernando Guerrero-Romero

Objective

Several cutoff points of the homeostasis model assessment of insulin resistance (HOMA-IR; varying from 2.5 to 4.0) have been suggested for diagnosing IR in youth. In this study, we determined the distribution of the HOMA-IR in Mexican children and adolescents.

Design and methods

A total of 6132 children and adolescents from San Luis Potosi, León, Queretaro, and Durango, which are cities in central and northern Mexico, were enrolled in a population-based cross-sectional study. Eligible participants were apparently healthy children and adolescents aged 6–18 years. Pregnancy and the presence of chronic illnesses were exclusion criteria.

Results

A total of 3701 (60.3%) girls and 2431 (39.7%) boys were included in this study. In the overall population, the mean body mass index, insulin levels, and fasting glucose levels were 21.8±1.3 kg/m2, 7.1±3.2 μU/ml, and 86.2±10.0 mg/dl respectively. The concentrations of insulin and fasting glucose gradually increased from 6 to 12 years of age, whereas the concentrations tended to plateau in the 13- to 18-year-old population. The absolute mean of the HOMA-IR was 2.89±0.7. The HOMA-IR gradually increased with age and reached a plateau at 13 years of age.

Conclusions

Because the insulin concentrations, glucose levels, and HOMA-IR exhibited a gradual increase with age that was not related to obesity, our results suggested that the evaluation of IR in children should be based on percentiles of the HOMA-IR rather than a dichotomous value derived from a single cutoff point.

Free access

BMI percentile-for-age overestimates adiposity in early compared with late maturing pubertal children

Kaspar Sørensen and Anders Juul

Objective

Early pubertal timing is consistently associated with increased BMI percentile-for-age in pubertal girls, while data in boys are more ambiguous. However, higher BMI percentile-for-age may be a result of the earlier puberty per se rather than vice versa. The aim was to evaluate markers of adiposity in relation to pubertal timing and reproductive hormone levels in healthy pubertal boys and girls.

Study design

Population-based cross-sectional study (The Copenhagen Puberty Study). Eight-hundred and two healthy Caucasian children and adolescents (486 girls) aged 8.5–16.5 years participated. BMI and bioelectric impedance analyses (BIA) were used to estimate adiposity. Clinical pubertal markers (Tanner stages and testicular volume) were evaluated. LH, FSH, estradiol, testosterone, SHBG and IGF1 levels were determined by immunoassays.

Results

In all age groups, higher BMI (all 1 year age-groups, P≤0.041) was found with early compared with late maturation, despite similar BIA–estimated body fat percentage (BIA–BF%). Neither BMI nor BIA–BF% differed for a given stage of maturation. BMI percentile-for-age and prevalence of overweight/obesity were higher in the early compared with late matured pubertal children (all P≤0.038), despite similar BIA–BF%. Pubertal girls with BIA–BF >29% had significantly lower LH and FSH levels compared with normal-weight girls (P≤0.041).

Conclusions

Early maturational timing was not associated with higher adiposity for a given stage of puberty. Using BMI percentile-for-age overestimated the degree of adiposity in early pubertal compared with late pubertal children.

Free access

Sex 'n' drugs 'n' rock 'n' roll: the meaning and social consequences of pubertal timing

A Waylen and D Wolke

This is a brief review of the normal changes in adolescent behaviour and the interplay between biology and social factors that occur at and around puberty, in an attempt to explain when this transition may become problematic The onset of puberty is a biological marker for an individual's transition from a non-reproductive to a reproductive state. Adolescence is a normal developmental transition associated with clearly visible physical changes, reorganization and pruning of neuronal circuits in the brain and the occurrence of new behaviours and interests. It is a time when new life tasks (orientation towards peers of the other sex, romantic and sexual involvement and mastering an educational career) need to be mastered. Parent-child conflict increases and becomes more intense as the adolescent struggles for more independence while still requiring support. These normal changes can become problematic if biological and social expectations diverge e.g. entering puberty very early or very late. While early pubertal onset in boys is likely to have beneficial effects, in girls precocious pubertal timing may have a negative impact on body-image, affect (or emotional well-being) and sex-role expectations. Other individual biological predispositions and genetic endowment may interact with social factors (e.g. peers, parenting style, neighbourhood) making adolescence either an adaptive or a challenging transition. There is a lack of sufficiently large longitudinal studies that have been able to study this interaction between genetics, biology and social environment on adolescent development. The Avon Longitudinal Study of Parents and Children (ALSPAC) cohort provides a unique opportunity to investigate the impact of pubertal timing on social behaviour. Planned assessments and concepts are outlined.

Free access

Acylation stimulating protein but not complement C3 associates with metabolic syndrome components in Chinese children and adolescents

Ponce Cedric Fouejeu Wamba, Jie Mi, Xiao-Yuan Zhao, Mei-Xian Zhang, Yu Wen, Hong Cheng, Dong-Qing Hou, and Katherine Cianflone

Objective

Childhood obesity is increasing worldwide and is increasingly associated with metabolic syndrome (MetS). Our aim was to examine acylation stimulating protein (ASP) and its precursor complement C3, in normal, overweight, and obese Chinese children and adolescents, and the relationships with body size, blood parameters, pubertal development, family environment, and MetS.

Methods

Children and adolescents (n=1603) from 6 to 18 years, boys (n=873) and girls (n=730), including normal weight (n=603), overweight (n=291) and obese (n=709) were assessed for body size parameters, pubertal development, blood lipids, glucose, insulin, ASP, and C3.

Results

ASP levels were increased in overweight and obese versus normal weight (P<0.001), while C3 showed little variation. This effect of overweight/obesity remained throughout early stages when boys and girls were separated by pubertal development or age, although age and pubertal status itself had no effect. Separation based on ASP quintiles demonstrated significant associations with blood cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-Chol), glucose, insulin, and homeostatic model assessment of insulin resistance in boys, and LDL-Chol, high-density lipoprotein cholesterol, and glucose in girls. A positive correlation with mother's body mass index in boys and girls (P=0.002 and P=0.014 respectively) as well as birth weight (P<0.001) was noted. MetS was strongly associated with increased ASP, the presence of a single MetS factor (especially hypertension, central obesity, or hyperglycemia) was associated with increased ASP.

Conclusion

Changes in the plasma adipokine ASP in early obesity are associated with blood lipid and glucose modifications, family environment, and distinct MetS risk factors.

Free access

Adult height of prepubertal short children born small for gestational age treated with GH

Myriam Rosilio, Jean-Claude Carel, Emmanuel Ecosse, and Jean-Louis Chaussainon

Group-author : on behalf of the 0908 Lilly Study Group

Objective: Human GH (hGH) treatment leads to catch-up growth in children with short stature born small for gestational age (SGA). However, long-term efficacy and safety results in this patient group remain scarce. The present study assessed the efficacy and safety of late childhood treatment with biosynthetic hGH (Humatrope) in a group of short children born SGA (height <−2 standard deviation scores (SDS)).

Design: Patients in this open-label, Phase III, multicenter study received a daily hGH dose of 0.067 mg/kg for 2 years, and then received no treatment for the following 2 years. After the fourth year on study, patients whose height had decreased more than 0.5 SDS but who still showed growth potential based on bone age were allowed to resume treatment until they reached adult height.

Methods: Height gain SDS was assessed for 11 girls and 24 boys (mean age±s.d. 9.6±0.9 years) at the end of the 2 years of hGH treatment, during the subsequent 2-year off-treatment period, and upon reaching adult height.

Results: At the end of the initial 2-year treatment period, 83% of patients had reached a height within the normal range, with a mean increase in height SDS vs baseline of 1.3±0.3 (P <0.001). Adult heights (n = 20) were within the normal range for 50% of patients, and mean height gain from baseline was statistically significant (0.7±0.8 SDS, P <0.001). Fasting glucose and glycosylated hemoglobin levels were not significantly modified during treatment.

Conclusions: High-dose hGH treatment for a minimum of 2 years in short children born SGA was well tolerated and resulted in a significant increase in adolescent and adult height.

Free access

Short boys treated with growth hormone show normal progression of testicular size and achieve normal serum testosterone concentrations

C Ankarberg-Lindgren, E Norjavaara, and KA Wikland

OBJECTIVE: To determine whether there is evidence for impaired testicular function at final height in short boys treated with growth hormone (GH) during their childhood and adolescence. STUDY DESIGN: The analysis was restricted to males who had isolated GH deficiency or idiopathic short stature, and who were included in the Swedish National Registry and the Swedish GH trials. The subjects had to have been treated with GH for at least 4 years; the treatment had to have been started prepubertally, given for at least one year before the onset of puberty and the subjects had to have reached final height. One hundred and eleven boys fulfilled the criteria. METHODS: Testicular volumes were determined by orchidometer in each boy when GH treatment was started and at final height. Samples for testosterone measurements were collected from 77 boys at final height, and were measured by RIA. RESULTS: Each subject had normal testicular size (15 ml or more) and for those in whom concentrations were determined, serum testosterone levels and diurnal rhythm were normal. CONCLUSIONS: The results of our survey do not show evidence of testicular impairment following GH therapy.

Free access

Increased serum soluble leptin receptor levels in children and adolescents with type 1 diabetes mellitus

J Kratzsch, A Deimel, A Galler, T Kapellen, A Klinghammer, and W Kiess

OBJECTIVE: We investigated whether or not serum levels of the soluble leptin receptor (sOB-R) and leptin are related to anthropometric and metabolic changes during pubertal development of children and adolescents with type 1 diabetes mellitus. DESIGN AND METHODS: Blood levels of sOB-R, leptin and HbA1C, as well as body-mass index (BMI), diabetes duration and daily insulin doses, were determined in 212 (97 girls; 115 boys) children with type 1 diabetes mellitus and compared with the sOB-R serum levels in 526 healthy children and adolescents. RESULTS: OB-R serum levels and parallel values of the molar ratio between sOB-R and leptin were significantly higher in children with diabetes than in normal children (P<0.05) in almost all investigated Tanner stages. Furthermore, in the entire group of patients, we demonstrated statistically significant correlations (P<0.02) between sOB-R and the duration of diabetes (r=0.30), HbA1c levels (r=0.32) and the insulin dose (r=0.18). Multiple-regression analysis revealed that HbA1c (12.4%), height (7.9%) and duration of diabetes (8.7%) contributed to 29% variance of sOB-R in diabetic children. CONCLUSIONS: Our data suggest that poor glycemic control in diabetes may lead to increased serum levels of sOB-R. This regulation of sOB-R appears to be independent of leptin, but may have an impact on leptin action. The consequently developing molar excess of sOB-R related to leptin could reduce leptin sensitivity and may, therefore, influence leptin-related anthropometric and metabolic abnormalities.

Free access

Serum leptin levels in children and adolescents with insulin-dependent diabetes mellitus in relation to metabolic control and body mass index

W Kiess, M Anil, WF Blum, P Englaro, A Juul, A Attanasio, J Dotsch, and W Rascher

The ob protein, termed leptin, is produced by adipocytes and is thought to act as an afferent satiety signal regulating weight through suppressing appetite and stimulating energy expenditure in humans and/or rodents. Insulin has been found to be a potent stimulator of leptin expression in rodents. It is unclear at present whether this insulin action is a direct or an indirect effect. To investigate whether leptin concentrations in children and adolescents with type 1 diabetes (IDDM) were related to metabolic status, body weight, body mass index and insulin treatment, we have measured leptin concentrations in serum from 13 newly diagnosed IDDM patients before the beginning of insulin treatment (8 girls, 5 boys, aged 4.7-17.5 years) and in 134 patients with IDDM during treatment (64 girls, 70 boys, aged 2.6-20.1 years) using a specific radioimmunoassay. The data from patients with diabetes were compared with normative data that were derived from a large cohort of healthy children and adolescents. Serum from children with newly diagnosed diabetes had significantly lower levels of leptin (mean 1.28+/-1.60 ng/ml, range 0.14-6.13 ng/ml) compared with healthy children (n=710) (mean 2.2 ng/ml, range 0.26-14.4ng/ml) and compared with insulin-treated children and adolescents (mean 5.18+/-5.48 ng/ml, range 0.26-29.77 ng/ml) (P<0.0001) even after adjustment for gender and body mass index (BMI). Serum leptin levels in patients with IDDM were significantly correlated with BMI (r=0.42, P<0.0001). Multiple regression analysis showed that age and BMI were significantly correlated with leptin levels, while duration of diabetes, mean HbA1c levels, insulin dose and plasma glucose, triglyceride and cholesterol levels were not. Females had higher serum leptin concentrations than males even when adjusted for BMI (P<0.0001). Surprisingly and most importantly, leptin levels in insulin-treated young adult (Tanner stage 5) patients were significantly higher than values found in the healthy nondiabetic reference population when adjusted for sex, Tanner stage and BMI. These findings suggest that leptin levels in IDDM patients show a similar dependency on adipose tissue and age as in healthy, normal children. The data provide evidence that insulin may be of importance as a regulator of serum leptin levels in vivo not only in rodents but also in humans. It is hypothesized that the elevated BMI-adjusted leptin levels in adolescents with IDDM could indicate either that these patients may be oversubstituted by the intensified insulin therapy that they are receiving or that their body composition and body fat content may differ from that of healthy adolescents in the sense that they have a relative increase in fat mass.