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      Testosterone Therapy in Adolescent Boys: The Need for a Structured Approach

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          Abstract

          Background: In adolescents, testosterone may have several effects including promotion of secondary sexual characteristics and pubertal growth, attainment of optimal muscle mass and peak bone mass, optimization of the metabolic profile, and psychosocial maturation and well-being. Summary: Testosterone therapy is a cornerstone of the management of hypogonadism in boys. Since the initial report of the chemical synthesis of testosterone, several formulations have continued to develop, and although many of these have been used in boys, none of them have been studied in detail in this age group. Given the wide ranging effects of testosterone, the level of evidence for their effects in boys and the heterogeneity of conditions that lead to early-onset hypogonadism, a standardized protocol for monitoring testosterone replacement in this age group is needed. Key Messages: In this review, we focus on the perceived benefits of androgen replacement in boys affected by pubertal delay and highlight the need to improve the health monitoring of boys who receive androgen replacement therapy, proposing different approaches based on the underlying pathophysiology.

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          Most cited references 159

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          Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis.

          Ageing in men is associated with a gradual decline in serum testosterone levels and a concomitant loss of muscle mass, accumulation of central adiposity, impaired mobility and increased risk of bone fractures. Whether androgen treatment might be beneficial in these subjects is still under debate. We have carried out a systematic review of randomized controlled trials (RCTs) evaluating the effects of testosterone (T) administration to middle-aged and ageing men on body composition, muscle strength, bone density, markers of bone metabolism and serum lipid profile. A comprehensive search of all published randomized clinical trials was performed using the MEDLINE, Cochrane Library, EMBASE and Current Contents databases. Guided by prespecified criteria, software-assisted data abstraction and quality assessed by two independent reviewers, 29 RCTs were found to be eligible. For each investigated variable, we reported the results of pooled estimates of testosterone treatment using the random effect model of meta-analysis. Heterogeneity, reproducibility and consistency of the findings across studies were explored using sensitivity and meta-regression analysis. Overall, 1,083 subjects were evaluated, 625 randomized to T, 427 to placebo and 31 to observation (control group). Weighted mean age was 64.5 years (range 49.9--77.6) and mean serum testosterone was 10.9 nmol/l (range 7.8--19). Testosterone treatment produced: (i) a reduction of 1.6 kg (CI: 2.5--0.6) of total body fat, corresponding to -6.2% (CI: 9.2--3.3) variation of initial body fat, (ii) an increase in fat free mass of 1.6 kg (CI: 0.6--2.6), corresponding to +2.7% (CI: 1.1--4.4) increase over baseline and (iii) no change in body weight. The effects of T on muscle strength were heterogeneous, showing a tendency towards improvement only at the leg/knee extension and handgrip of the dominant arm (pooled effect size=0.3 standard mean difference (SMD), CI: -0.0 to 0.6). Testosterone improved bone mineral density (BMD) at the lumbar spine by +3.7% (CI: 1.0--6.4%) compared to placebo, but not at the femoral neck, and produced a consistent reduction in bone resorption markers (pooled effect size = -0.6 SMD, CI: -1.0 to -0.2). Testosterone also reduced total cholesterol by 0.23 mmol/l (CI: -0.37 to -0.10), especially in men with lower baseline T concentrations, with no change in low density lipoprotein (LDL)-cholesterol. A significant reduction of high density lipoprotein (HDL)-cholesterol was found only in studies with higher mean T-values at baseline (-0.085 mmol/l, CI: -0.017 to -0.003). Sensitivity and meta-regression analysis revealed that the dose/type of T used, in particular the possibility of aromatization, explained the heterogeneity in findings observed on bone density and HDL-cholesterol among studies. The present analysis provides an estimate of the average treatment effects of testosterone therapy in middle-aged men. Our findings are sufficiently strong to justify further interventional studies focused on alternative targets of androgenic treatment carrying more stringent clinical implications, in particular the cardiovascular, metabolic and neurological systems.
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            Generation and characterization of androgen receptor knockout (ARKO) mice: an in vivo model for the study of androgen functions in selective tissues.

             S. Yeh,  M.-Y. Tsai,  Q Xu (2002)
            By using a cre-lox conditional knockout strategy, we report here the generation of androgen receptor knockout (ARKO) mice. Phenotype analysis shows that ARKO male mice have a female-like appearance and body weight. Their testes are 80% smaller and serum testosterone concentrations are lower than in wild-type (wt) mice. Spermatogenesis is arrested at pachytene spermatocytes. The number and size of adipocytes are also different between the wt and ARKO mice. Cancellous bone volumes of ARKO male mice are reduced compared with wt littermates. In addition, we found the average number of pups per litter in homologous and heterozygous ARKO female mice is lower than in wt female mice, suggesting potential defects in female fertility and/or ovulation. The cre-lox ARKO mouse provides a much-needed in vivo animal model to study androgen functions in the selective androgen target tissues in female or male mice.
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              Growth and maturation during adolescence.

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                Author and article information

                Journal
                HRP
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                1663-2818
                1663-2826
                2019
                March 2020
                18 December 2019
                : 92
                : 4
                : 215-228
                Affiliations
                aDepartment of Pediatrics, Endocrine Unit, Scientific Institute San Raffaele, Milan, Italy
                bDevelopmental Endocrinology Research Group, University of Glasgow, Glasgow, United Kingdom
                cDepartment of Pediatrics, University of Virginia, Charlottesville, Virginia, USA
                Author notes
                *S. Faisal Ahmed, MD, FRCPCH, School of Medicine, University of Glasgow, New South Glasgow University Hospital Campus, 1345 Govan Road, Glasgow G51 4TF (UK), E-Mail faisal.ahmed@glasgow.ac.uk
                Article
                504670 Horm Res Paediatr 2019;92:215–228
                10.1159/000504670
                31851967
                © 2019 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 1, Tables: 3, Pages: 14
                Categories
                Mini Review Article

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