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

Pubertal timing predicts leg length and childhood body mass index predicts sitting height in young adult men

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

Nocturnal application of transdermal estradiol patches produces levels of estradiol that mimic those seen at the onset of spontaneous puberty in girls

The objective of pubertal induction in children with hypogonadism is to mimic spontaneous puberty in terms of physical and psychological development. In a clinical observation study, we induced puberty in 15 girls with hyper- or hypogonadotropic hypogonadism using low doses of transdermal estradiol patches attached only during the night and compared the estradiol concentrations obtained with those in healthy girls. Pubertal induction was started between the ages of 12.3 and 18.1 yr. A transdermal matrix patch of 17 beta -estradiol (25 mug/24 h; Evorel, Janssen Pharmaceuticals-Cilag) was cut into pieces corresponding to 3.1, 4.2, or 6.2 mug/24 h initially and attached to the buttock. After 4-14 months, the dose was increased gradually. Serum 17 beta -estradiol concentrations were measured every 2 h by RIA (detection limit, 6.0 pmol/L; 1.6 pg/mL). The results show that it is possible to mimic the spontaneous levels as well as the diurnal pattern of serum 17 beta -estradiol in early puberty, by cutting a transdermal 17 beta -estradiol matrix patch and attaching a part of it, corresponding to 0.08-0.12 pg estradiol/kg BW, to the buttock nocturnally. In most of the girls, breast development occurred within 3- 6 months of the start of treatment

Comparison of methods for evaluation of the suppressive effects of prednisolone on the HPA axis and bone turnover: changes in s-DHEAS are as sensitive as the ACTH test

Objective: Different hypothalamic-pituitary-adrenal (HPA) axis function tests are used for diagnosing disease and evaluating suppressive effects of corticosteroid treatment. Our objectives were to evaluate sensitivity and precision of different HPA axis tests to be able to select one that combines good performance with good practicability, suitable for investigation of new corticosteroids in clinical trials. Methods: In this descriptive, double-blind, parallel-group study, 60 healthy male volunteers were treated with once-daily morning doses of prednisolone for 2 weeks. The volunteers were randomized to 1 of 5 treatment groups (prednisolone 2.5, 5, 7.5, 10, or 15 mg). We compared the plasma-cortisol (p-cortisol) 24-hour average concentration (C,) with morning (08:00 hours) p-cortisol, daytime p-cortisol C,, and 24-hour urinary cortisol excretion. Adrenocorticotrophic hormone (ACTH) stimulation tests and the metyrapone test were also performed. Furthermore, we analyzed levels of serum dehydroepiandrosterone sulfate (s-DHEAS), insulin, and markers of bone turnover. Results: Dose-related effects were shown, but the magnitude of effects and sensitivities varied greatly between the tests. P-cortisol measurements over the course of 24 hours were used as the reference method. Low- and standard-dose ACTH tests and morning s-DHEAS levels had similar sensitivity. Urinary cortisol excretion and the metyrapone stimulation test had low sensitivity. The effects of prednisolone on markers of bone turnover were, in general, less than those on the HPA axis. Only osteocalcin, procollagen type 1 C-peptide and procollagen type 3 N-peptide were significantly affected. Treatment with prednisolone was well tolerated. Conclusion: Changes in s-DHEAS and the low-dose ACTH test combine good sensitivity and precision for evaluation of the suppressive effect of exogenous corticosteroids on the HPA axis, and they are easy to perform

No association between inhaled corticosteroids and whole body DXA in postmenopausal women.

Purpose Postmenopausal women treated with corticosteroids are regarded as a high-risk group due to the effect of both natural bone loss and possible adverse effects of treatment with inhaled corticosteroids (IC). Objective To compare bone mineral density (BMD) in postmenopausal women exposed only to IC (IC group, n = 106) with that of BMD in women not exposed to corticosteroids (n = 124) and women exposed to oral and/or intra-articular injections in addition to inhaled corticosteroids (OC group, n = 3 1). The women were recruited from a population-based prospective cohort study. Methods Dual X-ray absorptiometry (DXA) technique was used to measure BMD in whole body, spine, pelvis and lower extremities. A health questionnaire and an interview about past and present medication use were used. Results The mean duration and dose of IC were 9.5 +/- 4.5 years and 615 mu g daily. Whole body BMD did not significantly differ between the IC group (1.103 g/cm(2)) and the unexposed group (1.087 g/cm(2)). Within the IC group, BMD stratified for cumulative dose of IC, duration or current dose above or below 800 jig did not differ. Z-score BMD for tertiles did not differ when comparing the IC and OC groups. Conclusion No difference in BMD was noted between postmenopausal women exposed to inhaled corticosteroids and unexposed controls nor was there any dose response relationship between inhaled corticosteroid therapy and BMD. Copyright (c) 2006 John Wiley & Sons, Ltd

Fat parameters according to age at AR tertiles.

<p>Histograms representing early, middle and late age at adiposity rebound tertiles for BMI (a), percentage body fat (b), whole body fat mass (c), serum leptin levels (d), Subcutaneous adipose tissue (ScAT; n = 194; e) and Intraperitoneal adipose tissue (IpAT; n = 194; f). Values are given as means ± SEM. BMI = Body Mass Index, **p<0.01, ***p<0.001.</p

Age at Adiposity Rebound Is Associated with Fat Mass in Young Adult Males—The GOOD Study

<div><h3>Objective</h3><p>Age at adiposity rebound (AR) is associated with obesity and Type 2 Diabetes in adults. The aim of the present study was to investigate the role of age at AR in adult fat mass, fat distribution and pubertal timing for a Swedish cohort.</p> <h3>Patients and Methods</h3><p>This is a retrospective cohort study. Detailed growth charts were retrieved for the men participating in the population-based GOOD (Gothenburg Osteoporosis and Obesity Determinants) study (n = 573). Body composition was analysed using dual X-ray absorptiometry and computed tomography at 18–20 years of age. Age and BMI at AR were calculated using pediatric growth charts and AR was defined as the lowest BMI between 3 and 9 years of age.</p> <h3>Results</h3><p>Subjects were divided into early (age at AR below 5.4 years of age), middle (age at AR 5.4 to 6.8 years of age) and late (age at AR after 6.8 years of age) age at AR tertiles. Subjects in the early age at AR tertile had higher young adult BMI (+8%), whole body fat mass (+34%) and amount of subcutaneous adipose tissue (+61%) than the subjects in the middle and late tertiles (p<0.01). The early age at AR tertile had an increased risk of obesity (Odds Ratio 4.1 [95% CI 1.2–13.9]) compared with the middle and late tertiles. In addition, the early age at AR tertile had Peak Height Velocity (PHV) 7 months earlier than the late tertile.</p> <h3>Conclusions</h3><p>Early age at AR was associated with young adult obesity as a consequence of a high amount of subcutaneous adipose tissue in men. In addition we made the novel observation that early age at AR was associated with an early puberty in men.</p> </div