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      Pubertal induction and transition to adult sex hormone replacement in patients with congenital pituitary or gonadal reproductive hormone deficiency: an Endo-ERN clinical practice guideline


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          An Endo-European Reference Network guideline initiative was launched including 16 clinicians experienced in endocrinology, pediatric and adult and 2 patient representatives. The guideline was endorsed by the European Society for Pediatric Endocrinology, the European Society for Endocrinology and the European Academy of Andrology. The aim was to create practice guidelines for clinical assessment and puberty induction in individuals with congenital pituitary or gonadal hormone deficiency. A systematic literature search was conducted, and the evidence was graded according to the Grading of Recommendations, Assessment, Development and Evaluation system. If the evidence was insufficient or lacking, then the conclusions were based on expert opinion. The guideline includes recommendations for puberty induction with oestrogen or testosterone. Publications on the induction of puberty with follicle-stimulation hormone and human chorionic gonadotrophin in hypogonadotropic hypogonadism are reviewed. Specific issues in individuals with Klinefelter syndrome or androgen insensitivity syndrome are considered. The expert panel recommends that pubertal induction or sex hormone replacement to sustain puberty should be cared for by a multidisciplinary team. Children with a known condition should be followed from the age of 8 years for girls and 9 years for boys. Puberty induction should be individualised but considered at 11 years in girls and 12 years in boys. Psychological aspects of puberty and fertility issues are especially important to address in individuals with sex development disorders or congenital pituitary deficiencies. The transition of these young adults highlights the importance of a multidisciplinary approach, to discuss both medical issues and social and psychological issues that arise in the context of these chronic conditions.

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          GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables.

          This article is the first of a series providing guidance for use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system of rating quality of evidence and grading strength of recommendations in systematic reviews, health technology assessments (HTAs), and clinical practice guidelines addressing alternative management options. The GRADE process begins with asking an explicit question, including specification of all important outcomes. After the evidence is collected and summarized, GRADE provides explicit criteria for rating the quality of evidence that include study design, risk of bias, imprecision, inconsistency, indirectness, and magnitude of effect. Recommendations are characterized as strong or weak (alternative terms conditional or discretionary) according to the quality of the supporting evidence and the balance between desirable and undesirable consequences of the alternative management options. GRADE suggests summarizing evidence in succinct, transparent, and informative summary of findings tables that show the quality of evidence and the magnitude of relative and absolute effects for each important outcome and/or as evidence profiles that provide, in addition, detailed information about the reason for the quality of evidence rating. Subsequent articles in this series will address GRADE's approach to formulating questions, assessing quality of evidence, and developing recommendations. Copyright © 2011 Elsevier Inc. All rights reserved.
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            GRADE guidelines: 3. Rating the quality of evidence.

            This article introduces the approach of GRADE to rating quality of evidence. GRADE specifies four categories-high, moderate, low, and very low-that are applied to a body of evidence, not to individual studies. In the context of a systematic review, quality reflects our confidence that the estimates of the effect are correct. In the context of recommendations, quality reflects our confidence that the effect estimates are adequate to support a particular recommendation. Randomized trials begin as high-quality evidence, observational studies as low quality. "Quality" as used in GRADE means more than risk of bias and so may also be compromised by imprecision, inconsistency, indirectness of study results, and publication bias. In addition, several factors can increase our confidence in an estimate of effect. GRADE provides a systematic approach for considering and reporting each of these factors. GRADE separates the process of assessing quality of evidence from the process of making recommendations. Judgments about the strength of a recommendation depend on more than just the quality of evidence. Copyright © 2011 Elsevier Inc. All rights reserved.
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              Variations in pattern of pubertal changes in girls.


                Author and article information

                Eur J Endocrinol
                Eur J Endocrinol
                European Journal of Endocrinology
                Bioscientifica Ltd (Bristol )
                29 March 2022
                01 June 2022
                : 186
                : 6
                : G9-G49
                [1 ]Pediatric Endocrinology , Department of Women’s and Children’s Health Karolinska Institutet, and Department of Pediatric Endocrinology and Inborn Errors of Metabolism, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden
                [2 ]Developmental Endocrinology Research Group , School of Medicine, Dentistry & Nursing, University of Glasgow, Royal Hospital for Children, Glasgow, UK
                [3 ]Division of Pediatric Endocrinology and Obesity Center CGG , Department of Pediatrics, Erasmus MC Sophia Children’s Hospital, Erasmus University Medical Center, Rotterdam, The Netherlands
                [4 ]Department of Endocrinology , Alder Hey Children’s Hospital, Liverpool, UK
                [5 ]Department of Medical Biotechnology and Translational Medicine , University of Milan, Milan, Italy
                [6 ]Department of Endocrine and Metabolic Diseases , IRCCS Istituto Auxologico Italiano, Milan, Italy
                [7 ]Pediatric Endocrinology Unit , Hôpital Universitaire des Enfants HUDERF, Université Libre de Bruxelles, Bruxelles, Belgium
                [8 ]Division of Endocrinology , Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
                [9 ]Department of Pediatric Endocrinology , Amalia Childrens Hospital, Radboud University Medical Centre, Nijmegen, The Netherlands
                [10 ]Department of Child and Adolescent Psychiatry and Psychology , Sophia Children’s Hospital Erasmus Medical Center, Rotterdam, Netherlands
                [11 ]Department of Internal Medicine and Pediatrics , Faculty of Medicine and Health Sciences, University Ghent, Ghent, Belgium
                [12 ]Department of Pediatrics and Pediatric Endocrinology , Faculty of Medical Sciences, Medical University of Silesia, Katowice, Poland
                [13 ]Department of Endocrinology and Internal Medicine , Aarhus University Hospital, Aarhus, Denmark
                [14 ]Department of Molecular Medicine , Aarhus University Hospital, Aarhus, Denmark
                [15 ]Department of Growth and Reproduction , Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark
                [16 ]International Research and Research Training Centre for Endocrine Disruption in Male Reproduction and Child Health (EDMaRC) and Department of Clinical Medicine , University of Copenhagen, Copenhagen, Denmark
                [17 ]Department of Biochemical , Experimental and Clinical Sciences ‘Mario Serio’, University of Florence, Florence, Italy
                [18 ]New Children’s Hospital , Pediatric Research Center, Helsinki University Hospital, and Research Program Unit, Faculty of Medicine, Stem Cells and Metabolism Research Program, University of Helsinki, Helsinki, Finland
                [19 ]Turner Syndrome Support Society in the UK , ePAG ENDO-ERN, UK
                [20 ]Department of Endocrinology and Reproductive Medicine , Pitié Salpêtriere Hospital, Paris, France
                [21 ]Sorbonne Université Médecine and Center for Endocrine Rare Disorders of Growth and Development and Center for Rare Gynecological Disorders , Paris, France
                [22 ]SOD ITALIA APS – Italian Patient Organization for Septo Optic Dysplasia and Other Neuroendocrine Disorders – ePAG ENDO-ERN , Rome, Italy
                [23 ]Department of Clinical Epidemiology , LUMC Leiden, Leiden, The Netherlands
                [24 ]Department of Clinical Epidemiology , Aarhus University, Aarhus, Denmark
                Author notes
                Correspondence should be addressed to A Nordenström; Email: Anna.Nordenstrom@ 123456ki.se
                Author information
                © The authors

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                : 25 January 2022
                : 29 March 2022
                Clinical Practice Guideline

                Endocrinology & Diabetes
                Endocrinology & Diabetes


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