Twenty-four hours secretion pattern of serum estradiol in healthy prepubertal and pubertal boys as determined by a validated ultra-sensitive extraction RIA

<p>Abstract</p> <p>Background</p> <p>The role of estrogens in male physiology has become evident. However, clinically useful normative data for estradiol secretion in boys has not previously been established due to the insensitivity of current methods used in clinical routine. By use of a validated ultra-sensitive extraction RIA, our aim was to establish normative data from a group consisting of healthy boys in prepuberty and during pubertal development.</p> <p>Methods</p> <p>Sixty-two 24-hours serum profiles (6 samples/24 hours) were obtained from 44 healthy boys (ages; 7.2–18.6 years) during their pubertal development, classified into five stages: prepuberty (testis, 1–2 mL), early (testis, 3–6 mL), mid (testis, 8–12 mL), late-1 (testis,15–25 mL, not reached final height) and late-2 (testis,15–25 mL, reached final height). Serum estradiol was determined by an ultra- sensitive extraction radioimmunoassay with detection limit 4 pmol/L and functional sensitivity 6 pmol/L.</p> <p>Results</p> <p>Mean estradiol concentrations during 24-hours secretion increased from prepuberty (median: <4 (5–95 percentiles: <4 – 7) pmol/L) to early puberty (6 (<4 – 12 pmol/L) but then remained relatively constant until a marked increase between mid-puberty (8 (4 – 17) pmol/L) and late-1 (21 (12 – 37) pmol/L) puberty, followed by a slower increase until late-2 puberty (32 (20 – 47) pmol/L). The diurnal rhythm of serum estradiol was non-measurable in pre- and early puberty, but discerned in mid-puberty, and become evident in late pubertal stages with peak values at 0600 to 1000 h.</p> <p>Conclusion</p> <p>With the use of an ultra-sensitive extraction RIA, we have provided clinically useful normative data for estradiol secretion in boys.</p

BMI Changes During Childhood and Adolescence as Predictors of Amount of Adult Subcutaneous and Visceral Adipose Tissue in Men: The GOOD Study

Objective. The amount of visceral adipose tissue is a risk factor for the metabolic syndrome. It is unclear how body mass index (BMI) changes during childhood and adolescence predict adult fat distribution. We hypothesized that there are critical periods during development for the prediction of adult subcutaneous and visceral fat mass by BMI changes during childhood and adolescence. Research Design and Methods. Detailed growth charts were retrieved for the men participating in the population-based Gothenburg Osteoporosis and Obesity Determinants (GOOD) study (n=612). Body composition was analysed using Dual X-Ray Absorptiometry and adipose tissue areas using abdominal computed tomography at 18-20 years of age. Results. The main finding in the present study was that subjects with increases in BMI Z-score of >1 SD during adolescence had, independent of prepubertal BMI, both larger subcutaneous (+138%; p1 SD during late childhood had larger amount adult subcutaneous adipose tissue (+83%;

Supplementary Material for: Pubertal Growth and Serum Testosterone and Estradiol Levels in Boys

<b><i>Background/Aims:</i></b> To study serum testosterone and estradiol in healthy boys in relation to growth during puberty up to peak height velocity (PHV). <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> 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

Use of inhaled corticosteroids and bone mineral density in a population based study: the Nord-Trondelag Health Study (the HUNT Study)

Conflicting results have been reported of the long-term effects of treatment with inhaled corticosteroids (ICS) on bone. The objective of this study was to compare ICS users and non-users regarding bone mineral density (BMD) in a large population. A total of 65 225 adults participated in a cross-sectional study in the Nord-Trondelag Health Study 1995-1997. Those reporting asthma or asthma-related symptoms, were invited to have bone densitometry of the forearm, flow volume spirometry and a personal interview. Altogether 4482 women and 4142 men participated, of whom 2113 reported ever use and 6511 never use of ICS. Never-users of corticosteroids had a mean BMD, adjusted for confounders (age, square age, sex, body mass index, height, physical activity, work load, packyears, family history of osteoporosis and in women number of years since menopause and use of hormone replacement therapy), of 0.493 g/cm(2) at the distal site. Subjects having only used ICS or combined with courses of prednisolone, had 0.008 g/cm(2) (95% Cl: 0.005-0.011) lower BMD whilst users of prednisolone greater than or equal to6 months had 0.038 g/cm(2) (0.021-0.055) lower level. No dose response association between ICS and BMD, or difference in BMD by type of ICS was found. The association between CS use and BMD was independent of the measuring site. ICS use was associated with lower BMD. The lack of dose response in this study might be due to a narrow dose range or indicates that other characteristics of the patient group are contributing to the observed difference in ICS users compared to never-users. Copyright (C) 2004 John Wiley Sons, Ltd

Supplementary Material for: Estradiol and Pubertal Growth in Girls

<b><i>Aim:</i></b> The objective of this study was to determine estradiol levels and assess their relationship to pubertal growth in girls. <b><i>Methods:</i></b> 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). <b><i>Inclusion Criteria:</i></b> Birth weight and length above –2 SDS, gestational age 37–42 weeks, prepubertal height and weight within ±3 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. <b><i>Results:</i></b> 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, EC₅₀, 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. <b><i>Conclusions:</i></b> Morning 17β-estradiol in the low early pubertal range (13–31 pmol/l) is associated with increasing growth velocity

Tolerability, pharmacokinetics, and pharmacodynamics of the glucokinase activator AZD1656, after single ascending doses in healthy subjects during euglycemic clamp

Item does not contain fulltextOBJECTIVES: AZD1656 is a novel glucokinase activator with a postulated dual mechanism of action by activating glucokinase in both the pancreas and the liver, and with the potential to deliver effective glucose-lowering in Type 2 diabetes mellitus. Here, we present the tolerability, pharmacokinetics and pharmacodynamics of AZD1656 in two single-blind, randomized, placebocontrolled studies, one with Western and the other with Japanese healthy adult male subjects. METHODS: Both studies evaluated oral single ascending doses of AZD1656 of up to 180 mg, administered during euglycemic clamp conditions to explore a wide dose range without risking hypoglycemia. Safety, pharmacokinetics and effects on serum insulin and glucose infusion rate were assessed. A population pharmacokinetics analysis was also conducted. RESULTS: AZD1656 was well tolerated in single doses up to 180 mg in both populations. AZD1656 was rapidly absorbed, and a dose-proportional increase in total exposure was observed for AZD1656 and the equipotent metabolite, AZD5658. Taking differences in body weight into account, there were no differences in pharmacokinetic parameters between Western and Japanese subjects. A dose-dependent blood glucose lowering effect was indirectly demonstrated by the increased glucose infusion rate required to maintain euglycemia, which was of similar magnitude in both populations. Dose-dependent increases in insulin secretion were also observed. CONCLUSIONS: No safety concerns were raised. AZD1656 displayed uncomplicated pharmacokinetics and dose-dependent pharmacodynamics effects were observed. The results suggest no ethnic differences in AZD1656 tolerability, pharmacokinetics or pharmacodynamics