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Sophie van Rijn Clinical Neurodevelopmental Sciences, Leiden University, Wassenaarseweg, Leiden, The Netherlands
TRIXY Center of Expertise, Leiden University Treatment and Expertise Centre (LUBEC), Sandifortdreef, Leiden, The Netherlands
Leiden Institute for Brain and Cognition, Leiden University, Wassenaarseweg, Leiden, The Netherlands

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Kimberly Kuiper Clinical Neurodevelopmental Sciences, Leiden University, Wassenaarseweg, Leiden, The Netherlands
TRIXY Center of Expertise, Leiden University Treatment and Expertise Centre (LUBEC), Sandifortdreef, Leiden, The Netherlands
Leiden Institute for Brain and Cognition, Leiden University, Wassenaarseweg, Leiden, The Netherlands

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Nienke Bouw Clinical Neurodevelopmental Sciences, Leiden University, Wassenaarseweg, Leiden, The Netherlands
TRIXY Center of Expertise, Leiden University Treatment and Expertise Centre (LUBEC), Sandifortdreef, Leiden, The Netherlands
Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, Sophia Children’s Hospital, Dr. Molewaterplein, Rotterdam, The Netherlands

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Evelien Urbanus Clinical Neurodevelopmental Sciences, Leiden University, Wassenaarseweg, Leiden, The Netherlands
TRIXY Center of Expertise, Leiden University Treatment and Expertise Centre (LUBEC), Sandifortdreef, Leiden, The Netherlands
Department of Clinical, Neuro, and Developmental Psychology, Vrije Universiteit Amsterdam, Van der Boechorststraat, Amsterdam, The Netherlands

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Hanna Swaab Clinical Neurodevelopmental Sciences, Leiden University, Wassenaarseweg, Leiden, The Netherlands
TRIXY Center of Expertise, Leiden University Treatment and Expertise Centre (LUBEC), Sandifortdreef, Leiden, The Netherlands
Leiden Institute for Brain and Cognition, Leiden University, Wassenaarseweg, Leiden, The Netherlands

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vulnerability as well as the recognition of specific targets for early intervention. The TRIXY Early Childhood Study is a longitudinal study designed to identify early neurodevelopmental risks in children with SCT. Based on studies in adolescents and adults

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Hans Valdemar López Krabbe Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Jørgen Holm Petersen Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark

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Louise Laub Asserhøj Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Department of Fertility, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

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Trine Holm Johannsen Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Peter Christiansen Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Rikke Beck Jensen Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

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Line Hartvig Cleemann Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Casper P Hagen Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Lærke Priskorn Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Niels Jørgensen Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Katharina M Main Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

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Anders Juul Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

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Lise Aksglaede Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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endocrinology in Denmark. Boys with KS are followed with annual or biennial visits during childhood. The clinical examination is individualized but generally includes anthropometric measurements, testicular evaluation, rough neurological evaluation, and

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Alan D Rogol Department of Pediatrics, University of Virginia, Charlottesville, Virginia, USA

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axis at level of ovary) Increased incidence of autoimmunity ↑LH, FSH to GnRH stimulation 47,XXY Tall stature (onset may be in mid-childhood) Mini-puberty-contradictory results Childhood-↑INH B; Accelerated germ cell loss at

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Sebastian Franik Department of Obstetrics and Gynaecology, Radboudumc, Nijmegen, The Netherlands

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Kathrin Fleischer Department of Obstetrics and Gynaecology, Radboudumc, Nijmegen, The Netherlands

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Barbara Kortmann Department of Pediatric Urology, Radboudumc, Nijmegen, The Netherlands

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Nike M Stikkelbroeck Department of Internal Medicine, Radboudumc, Nijmegen, The Netherlands

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Kathleen D’Hauwers Department of Urology, Radboudumc, Nijmegen, The Netherlands

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Claire Bouvattier Department of Pediatric Endocrinology, Bicêtre Hospital, Paris Sud University, Paris, France

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Jolanta Slowikowska-Hilczer Department of Andrology and Reproductive Endocrinology, Medical University of Lodz, Lodz, Poland

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Solange Grunenwald Department of Endocrinology and Metabolic Disease, Centre Hospitalier Universitaire de Toulouse, Toulouse, France

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Tim van de Grift Departments of Plastic Surgery and Medical Psychology, Amsterdam UMC Location VUmc, Amsterdam, The Netherlands

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Audrey Cartault Department of Pediatrics, Hospital des Enfants, Toulouse, France

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Annette Richter-Unruh Kinderendokrinologie und Diabetologie, Universitätsklinikum Ruhr-Universität Bochum, Kinderklinik, Bochum, Germany

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Nicole Reisch Medizinische Klinik and Poliklinik IV, Department of Endocrinology, University Hospital Munich, Munich, Germany

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Ute Thyen Klinik fur Kinder- und Jugendmedizin, Universitat zu Lubeck, Lubeck, Germany

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Joanna IntHout Department for Health Evidence, Radboudumc, Nijmegen, The Netherlands

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Hedi L Claahsen-van der Grinten Department of Pediatric Endocrinology, Amalia Childrens Hospital, Radboudumc, Nijmegen, The Netherlands

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the dsd-LIFE Group
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the dsd-LIFE Group

 Age at diagnosis ‘At what age was your condition diagnosed?’ SC Before birth At birth (0 to 1 month) Infancy (1 month to 3 years) Childhood (4 to 12 years) Adolescence (13 to 17 years

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Kimberly Kuiper Clinical Neurodevelopmental Sciences, Leiden University, Leiden, The Netherlands
Leiden Institute for Brain and Cognition, Leiden, The Netherlands

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Hanna Swaab Clinical Neurodevelopmental Sciences, Leiden University, Leiden, The Netherlands
Leiden Institute for Brain and Cognition, Leiden, The Netherlands

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Nicole Tartaglia eXtraordinarY Kids Clinic, Developmental Pediatrics, Children’s Hospital Colorado, Aurora, Colorado
Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado

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Sophie van Rijn Clinical Neurodevelopmental Sciences, Leiden University, Leiden, The Netherlands
Leiden Institute for Brain and Cognition, Leiden, The Netherlands

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complex situations (action-oriented) ( 9 ). It is thus not surprising that the increasing ability to regulate emotions in childhood is associated with adaptive outcomes in multiple domains, including school readiness ( 10 ), better social skills ( 11

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Andre Madsen Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Anders Juul Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

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Lise Aksglaede Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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cardiovascular disease that are associated with increased morbidity and mortality ( 2 , 3 ). However, the phenotypic spectrum of KS is very wide, and especially during childhood the symptoms are often very subtle, and less than 10% of the expected number are

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Pamela Stratton Office of the Clinical Director, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA

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Neelam Giri Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

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Sonia Bhala Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

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Martha M Sklavos Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA

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Blanche P Alter Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

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Sharon A Savage Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

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Ligia A Pinto Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA

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AMH and testosterone produced by the testes ( 18 ). In males, AMH levels drop for a short time after birth, peak within 3–6 months of age, and are maintained consistently throughout infancy to childhood, and then fall prior to puberty ( 19 ). AMH

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Sebastian Franik Department of Obstetrics and Gynaecology, Radboudumc, Nijmegen, The Netherlands

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Kathrin Fleischer Department of Obstetrics and Gynaecology, Radboudumc, Nijmegen, The Netherlands

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Barbara Kortmann Department of Pediatric Urology, Radboudumc, Nijmegen, The Netherlands

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Nike M Stikkelbroeck Department of Internal Medicine, Radboudumc, Nijmegen, The Netherlands

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Kathleen D’Hauwers Department of Urology, Radboudumc, Nijmegen, The Netherlands

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Claire Bouvattier Department of Pediatric Endocrinology, Bicêtre Hospital, Paris Sud University, France

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Jolanta Slowikowska-Hilczer Department of Andrology and Reproductive Endocrinology, Medical University of Lodz, Poland

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Solange Grunenwald Department of Endocrinology and Metabolic Disease, Centre Hospitalier Universitaire de Toulouse, France

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Tim van de Grift Departments of Plastic Surgery and Medical Psychology, Amsterdam UMC location VUmc, Amsterdam, The Netherlands

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Audrey Cartault Department of Pediatrics, Hospital Des Enfants, Toulouse, France

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Annette Richter-Unruh Kinderendokrinologie und Diabetologie, Universitätsklinikum Ruhr-Universität Bochum, Kinderklinik, Bochum, Germany

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Nicole Reisch Department of Endocrinology, Medizinische Klinik and Poliklinik IV, University Hospital Munich, Munich, Germany

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Ute Thyen Klinik fur Kinder- und Jugendmedizin, Universitat zu Lubeck, Ratzeburger Allee, Lubeck, Germany

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Joanna IntHout Department for Health Evidence, Radboudumc, Nijmegen, The Netherlands

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Hedi L Claahsen-van der Grinten Department of Pediatric Endocrinology, Amalia Childrens Hospital, Radboudumc, Nijmegen, The Netherlands

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the dsd-LIFE group
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‘Are you on testosterone therapy at present? SC Yes No Age at diagnosis ‘At what age was your condition diagnosed?’ SC Before birth At birth (0–1 month) Infancy (1 month–3 years) Childhood (4

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Claus H Gravholt Department of Endocrinology, Aarhus University Hospital, Aarhus, Denmark
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

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Alberto Ferlin Department of Medicine, Unit of Andrology and Reproductive Medicine, University of Padova, Padova, Italy

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Joerg Gromoll Centre of Reproductive Medicine and Andrology, Münster, Germany

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Anders Juul Department of Growth and Reproduction Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

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Armin Raznahan Section on Developmental Neurogenomics, National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, Maryland, USA

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Sophie van Rijn Clinical Neurodevelopmental Sciences, Leiden University, Leiden, The Netherlands and TRIXY Center of Expertise, Leiden University Treatment and Expertise Centre (LUBEC), Leiden, The Netherlands

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Alan D Rogol Department of Pediatrics, University of Virginia, Charlottesville, Virginia, USA

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Anne Skakkebæk Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark

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Nicole Tartaglia Department of Pediatrics, Developmental Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA

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Hanna Swaab Clinical Neurodevelopmental Sciences, Leiden University, Leiden, The Netherlands and TRIXY Center of Expertise, Leiden University Treatment and Expertise Centre (LUBEC), Leiden, The Netherlands

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during childhood ( 30 , 31 , 32 ) and into adulthood ( 29 , 33 , 34 ). A study in children showed a positive effect of oxandrolone treatment on fat mass ( 35 ) and in adults, a small randomized controlled trial (RCT) also showed decreases in fat mass

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Lukas Ochsner Ridder Department of Endocrinology and Internal Medicine and Medical Research Laboratories, Aarhus University Hospital, Aarhus, Denmark
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark

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Agnethe Berglund Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Genetics and Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark

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Kirstine Stochholm Department of Endocrinology and Internal Medicine and Medical Research Laboratories, Aarhus University Hospital, Aarhus, Denmark

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Simon Chang Department of Endocrinology and Internal Medicine and Medical Research Laboratories, Aarhus University Hospital, Aarhus, Denmark
Unit for Thrombosis Research, Hospital of South West Jutland and University of Southern Denmark, Esbjerg, Denmark

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Claus H Gravholt Department of Endocrinology and Internal Medicine and Medical Research Laboratories, Aarhus University Hospital, Aarhus, Denmark
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
Unit for Thrombosis Research, Hospital of South West Jutland and University of Southern Denmark, Esbjerg, Denmark

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childhood – with no difference between pre- and postnatally diagnosed boys. Using measures of inhibin B and anti-Müllerian hormone (AMH) as a measure of testicular function, the authors reported a blunted rise in inhibin B in 47,XYY in early puberty compared

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