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Birzniece V.,Garvan Institute of Medical Research | Birzniece V.,University of New South Wales | Meinhardt U.J.,Garvan Institute of Medical Research | Meinhardt U.J.,Center for Pediatric Endocrinology Zurich | And 8 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Context: GHdeficiency causes reduction in muscle and bone mass and an increase in fat mass (FM), the changes reversed by GH replacement. The beneficial effects of GH on fat oxidation and protein anabolism are attenuatedmoremarkedlybyraloxifene,aselective estrogen receptor modulator,compared with 17β-estradiol. Whether this translates to a long-term detrimental effect on body composition is unknown. Objective: Our objective was to compare the effects of 17β-estradiol and raloxifene on FM, lean body mass (LBM), and bone mineral density (BMD) during GH replacement. Design: This was an open-label randomized crossover study. Patients and intervention: Sixteen hypopituitary women received GH (0.5 mg/d) replacement for 24 months. One group received 17β-estradiol (2 mg/d) for the first 6 months before crossover to raloxifene (60 mg/d) for the remaining 18 months; the other received the reversed sequence. Main Outcome Measures: Serum IGF-I and IGF-binding protein-3 concentrations, and FM, LBM, lumbar spine and femoral neck BMD were analyzed at baseline and at 6, 12, and 24 months within and between subjects. Results: GH therapy significantly increased mean IGF-I during 17β-estradiol and raloxifene co-treatments equally, but elevated IGF-binding protein-3 to a greater extent during raloxifene cotreatment. GH cotreatment with 17β-estradiol increased LBM and lumbar spine and femoral neck BMD and reduced FM to a greater extent than with raloxifene. Conclusions: In hypopituitary women, raloxifene at therapeutic doses significantly attenuated the beneficial effects of GH on body composition compared with 17β-estradiol. Raloxifene has no metabolic advantage over 17β-estradiol during GH replacement. Copyright © 2012 by The Endocrine Society. Source

Meinhardt U.,Center for Pediatric Endocrinology Zurich | Eiholzer U.,Center for Pediatric Endocrinology Zurich | Seitz L.,Novo Nordisk AS | Bogelund M.,Holte Stationsvej 14 | Kappelgaard A.-M.,Novo Nordisk AS
Expert Review of Medical Devices | Year: 2014

Sustained treatment adherence, usually over long periods of time, is critical to the success of growth hormone (GH) therapy. However, adherence rates are often poor which may result in suboptimal clinical outcomes. The type of device used by patients to administer their GH can influence adherence. Offering patients a choice of device maximizes the chance of adherence to treatment. Multiple factors will influence a patient's choice of device, depending on individual priorities. This study evaluated the most preferred features of GH injection devices by parents using a web-based questionnaire and as assessed by their willingness to pay for specific device features. The results show that parents are willing to pay for device features facilitating ease of use. © 2014 Informa UK Ltd. Source

Meinhardt U.,Center for Pediatric Endocrinology Zurich | Christiansen J.S.,Aarhus University Hospital | Farholt S.,Aarhus University Hospital | Lammer C.,Childrens Hospital | And 4 more authors.
Hormone and Metabolic Research | Year: 2013

Prader-Willi syndrome is a genetic disorder that is associated with short stature, partial growth hormone deficiency, small hands and feet, learning and behavioural problems, and hyperphagia leading to severe, often morbid, obesity. Growth hormone therapy is associated with an improvement in height and body composition. We evaluated the efficacy and safety of long-term growth hormone treatment in a retrospective observational multinational study of 41 prepubertal children (mean age 3.8±3.0 years) with genetically diagnosed Prader-Willi syndrome treated with growth hormone (0.03-0.06 mg/kg/day) for >12 months [mean duration 4.1 (range 0.9-9.5) years]. Height, weight, and body composition measurements were recorded at baseline and at 6 month intervals until last observation. Mean (SD) gain in height at 12 months was 0.9 (0.2) SD score (p<0.0001). At last observation (after approximately 6 years) mean gain in height was 1.3 (0.3) (p=0.0001) with 85% of children achieving height>- 2 SD score. Body composition improved during treatment with an estimated 9.1% increase in lean body mass and 9.1% decrease in fat mass at last observation (p=0.019). Scoliosis was reported in 3 patients at baseline and 8 patients at last observation. Sleep apnoea was recorded in 3 (7.3%) patients. There were no other severe adverse events reported. Long-term growth hormone treatment of prepubertal children with Prader-Willi syndrome was associated with significant improvements in height and body composition. Treatment was well tolerated. The development of scoliosis warrants monitoring by an orthopaedic specialist. © 2013 Georg Thieme Verlag KG Stuttgart . New York. Source

Birzniece V.,Garvan Institute of Medical Research | Meinhardt U.,Garvan Institute of Medical Research | Meinhardt U.,Center for Pediatric Endocrinology Zurich | Gibney J.,Garvan Institute of Medical Research | And 6 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2010

Context: The metabolic action of GH is attenuated by estrogens administered via the oral route. Selective estrogen receptor modulators lower IGF-I to a lesser degree than 17β-estradiol in GH-deficient women, and their effect on fat and protein metabolism is unknown. Objective: The aim of the study was to compare the modulatory effects of 17β-estradiol and raloxifene, a selective estrogen receptor modulator, on the metabolic action of GH. Design: We conducted an open-label, two-group, randomized, two-period crossover study. Patients and Intervention: Ten hypopituitary women received GH therapy alone (0.5 mg/d) and GH plus17β-estradiol (E2;2mg/d). Eleven hypopituitary women received GH therapy alone and GH plus raloxifene (R; 60 mg/d). The treatment duration was 1 month, with a 4-wk washout period. Main Outcome Measures: IGF-I, IGFBP-3, resting energy expenditure, and fat oxidation were quantified by indirect calorimetry. We measured whole body leucine turnover from which leucine rate of appearance and leucine incorporation into protein were estimated. Results: GH significantly stimulated all outcome measures. During GH treatment, addition of R significantly reduced mean IGF-I but not IGFBP-3, whereas E2 reduced both IGF-I and IGFBP-3 levels. Cotreatment with R but not E2 significantly attenuated the stimulatory effects of GH on fat oxidation. Therewasa strong trend (P = 0.08) toward a greater reduction in leucine incorporation into protein after R compared to E2 cotreatment. Conclusions: The modulatory effects of E2 and R at therapeutic doses on GH action are different. R during GH therapy exerts a greater inhibitory effect on lipid oxidation and protein anabolism compared to E2. Copyright © 2010 by The Endocrine Society. Source

Eiholzer U.,Center for Pediatric Endocrinology Zurich | Meinhardt U.,Center for Pediatric Endocrinology Zurich | Petro R.,Center for Pediatric Endocrinology Zurich | Witassek F.,Center for Pediatric Endocrinology Zurich | And 2 more authors.
Journal of Pediatrics | Year: 2010

Objective: To test the hypothesis that resistance training may increase spontaneous physical activity in children. Study design: Two junior ice hockey teams were randomly assigned to unchanged training schedules (team ZSC, 21 boys; mean age, 13.2 years) or to participate twice weekly in guided resistance training for 4 months (team GCK, 25 boys; mean age, 13.4 years). Spontaneous physical activity energy expenditure (SpAEE; 3-axial accelerometry for 7 days), muscle strength, and body composition (dual energy x-ray absorptiometry) were measured at 0, 4, and 12 months. Results: Baseline measures did not differ in the groups, except for higher leg and trunk strength in team ZSC. In the intervention group compared with the control group, SpAEE significantly (P ≤ .02) increased at 4 months (+25.5% versus 0%) and 12 months (+13.5% versus -9.5%). Leg and arm strength increased because of training intervention; all other variables were unchanged. None of these variables correlated with changes in SpAEE. Conclusion: In boys who play ice hockey, spontaneous physical activity is inducible with resistance training; this effect seems to be independent of changes in body composition and strength. If this was confirmed in unselected children, resistance training might be a new strategy for childhood obesity prevention programs. © 2010 Mosby, Inc. All rights reserved. Source

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