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Johanna Christina Penell Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden
Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden

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Mark M Kushnir Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah, USA
ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah, USA

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Lars Lind Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden

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Jonatan Bergquist Department of Chemistry – BMC, Analytical Chemistry, Uppsala University, Uppsala, Sweden

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Jonas Bergquist Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah, USA
Department of Chemistry – BMC, Analytical Chemistry, Uppsala University, Uppsala, Sweden

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P Monica Lind Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden

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Tord Naessen Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden

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testosterone concentrations in older men have been associated with reduced all-cause mortality and higher dihydrotestosterone (DHT) with reduced ischemic heart disease mortality ( 11 ). Estrone is the most prevalent estrogen in menopause and has less intra- and

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Maki Igarashi Medical Support Center for Japan Environmental and Children’s Study, National Center for Child Health and Development, Setagaya, Tokyo, Japan
Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Setagaya, Tokyo, Japan

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Tadayuki Ayabe Medical Support Center for Japan Environmental and Children’s Study, National Center for Child Health and Development, Setagaya, Tokyo, Japan
Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Setagaya, Tokyo, Japan

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Kiwako Yamamoto-Hanada Medical Support Center for Japan Environmental and Children’s Study, National Center for Child Health and Development, Setagaya, Tokyo, Japan

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Keiko Matsubara Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Setagaya, Tokyo, Japan

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Hatoko Sasaki Medical Support Center for Japan Environmental and Children’s Study, National Center for Child Health and Development, Setagaya, Tokyo, Japan

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Mayako Saito-Abe Medical Support Center for Japan Environmental and Children’s Study, National Center for Child Health and Development, Setagaya, Tokyo, Japan

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Miori Sato Medical Support Center for Japan Environmental and Children’s Study, National Center for Child Health and Development, Setagaya, Tokyo, Japan

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Nathan Mise Department of Environmental and Preventive Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan

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Akihiko Ikegami Department of Environmental and Preventive Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan

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Masayuki Shimono Regional Center for Pilot Study of Japan Environment and Children’s Study, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan

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Reiko Suga Regional Center for Pilot Study of Japan Environment and Children’s Study, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan

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Shouichi Ohga Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
Research Center for Environment and Developmental Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan

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Masafumi Sanefuji Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan
Research Center for Environment and Developmental Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan

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Masako Oda Department of Public Health, Faculty of Life Sciences, Kumamoto University, Chuo-ku, Kumamoto, Japan

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Hiroshi Mitsubuchi Department of Neonatology, Kumamoto University Hospital, Chuo-ku, Kumamoto, Japan

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Takehiro Michikawa Japan Environment and Children’s Study Programme Office, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan

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Shin Yamazaki Japan Environment and Children’s Study Programme Office, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan

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Shoji Nakayama Japan Environment and Children’s Study Programme Office, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan

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Yukihiro Ohya Medical Support Center for Japan Environmental and Children’s Study, National Center for Child Health and Development, Setagaya, Tokyo, Japan

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Maki Fukami Medical Support Center for Japan Environmental and Children’s Study, National Center for Child Health and Development, Setagaya, Tokyo, Japan
Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Setagaya, Tokyo, Japan

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). Subsequently, an increase in circulating gonadal steroids (‘gonadarche’) takes place in a sex-specific manner. In girls, blood levels of estradiol (E 2 ) start to increase around 8 years of age, while in boys, testosterone levels typically increase at 9 years

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Shanlee M Davis Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA
eXtraOrdinarY Kids Clinic, Children's Hospital Colorado, Aurora, Colorado, USA

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Rhianna Urban Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA

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Angelo D’Alessandro Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado, USA

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Julie A Reisz Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado, USA

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Christine L Chan Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA

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Megan Kelsey Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA

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Susan Howell Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA
eXtraOrdinarY Kids Clinic, Children's Hospital Colorado, Aurora, Colorado, USA

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Nicole Tartaglia Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA
eXtraOrdinarY Kids Clinic, Children's Hospital Colorado, Aurora, Colorado, USA

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Philip Zeitler Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA
eXtraOrdinarY Kids Clinic, Children's Hospital Colorado, Aurora, Colorado, USA

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Peter Baker II Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA

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hypogonadism, a nearly universal finding in adult men with KS, has been implicated as the underlying pathologic mechanism leading to this increased risk ( 2 ). As an anabolic steroid, testosterone has effects on body composition and mitochondrial metabolism

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Jennifer K Y Ko Department of Women’s Health, University College London Hospital, London, UK

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Thomas F J King Department of Women’s Health, University College London Hospital, London, UK

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Louise Williams Department of Women’s Health, University College London Hospital, London, UK

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Sarah M Creighton Department of Women’s Health, University College London Hospital, London, UK

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Gerard S Conway Department of Women’s Health, University College London Hospital, London, UK

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use of testosterone, which in this situation is used as a prohormone providing oestradiol via aromatisation. As women with CAIS do not have a uterus, progesterone is not required. Based on our clinical experience, interest in the use of testosterone

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Pravik Solanki Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Australia
Alfred Health, Melbourne, Victoria, Australia

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Beng Eu Prahran Market Clinic, Victoria, Australia
Department of General Practice, Melbourne Medical School, The University of Melbourne, Victoria, Australia

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Jeremy Smith Faculty of Science, University of Western Australia, Perth, Australia

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Carolyn Allan Hudson Institute of Medical Research, Melbourne, Victoria, Australia

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Kevin Lee Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Australia

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testosterone replacement therapy ( 5 ). The severity of ASIH depends on the type, combination, timeframe and dosages of AAS being abused, which can vary considerably between abusers ( 6 ). Up to 90% may combine various forms of AAS, otherwise known as

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Eleftherios E Deiktakis Laboratory of Clinical Chemistry, School of Medicine, University of Crete, Heraklion, Greece

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Eleftheria Ieronymaki Laboratory of Clinical Chemistry, School of Medicine, University of Crete, Heraklion, Greece

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Peter Zarén Department of Translational Medicine, Lund University, Malmö, Sweden

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Agnes Hagsund Department of Translational Medicine, Lund University, Malmö, Sweden

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Elin Wirestrand Department of Translational Medicine, Lund University, Malmö, Sweden

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Johan Malm Department of Translational Medicine, Lund University, Malmö, Sweden

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Christos Tsatsanis Laboratory of Clinical Chemistry, School of Medicine, University of Crete, Heraklion, Greece

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Ilpo T Huhtaniemi Department of Translational Medicine, Lund University, Malmö, Sweden
Imperial College London, Institute of Reproductive and Developmental Biology, London, UK

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Aleksander Giwercman Department of Translational Medicine, Lund University, Malmö, Sweden
Malmö University Hospital, Reproductive Medicine Center, Malmö, Sweden

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Yvonne Lundberg Giwercman Department of Translational Medicine, Lund University, Malmö, Sweden

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Introduction For decades, gonadotropin-releasing hormone (GnRH) agonists have formed the mainstay hormonal treatment of prostate cancer ( 1 ). While they generate suppression of testosterone due to persistent suppression of luteinizing hormone

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Henrik Ryberg Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden
Sahlgrenska Osteoporosis Centre, Center for Bone and Arthritis Research (CBAR), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Anna-Karin Norlén Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden
Sahlgrenska Osteoporosis Centre, Center for Bone and Arthritis Research (CBAR), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Andreas Landin Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden
Sahlgrenska Osteoporosis Centre, Center for Bone and Arthritis Research (CBAR), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Per Johansson Sahlgrenska Osteoporosis Centre, Center for Bone and Arthritis Research (CBAR), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Zeinab Salman Sahlgrenska Osteoporosis Centre, Center for Bone and Arthritis Research (CBAR), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Anders Wallin Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden

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Johan Svensson Sahlgrenska Osteoporosis Centre, Center for Bone and Arthritis Research (CBAR), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
Department of Endocrinology, Skaraborg Central Hospital, Skövde, Sweden

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Claes Ohlsson Sahlgrenska Osteoporosis Centre, Center for Bone and Arthritis Research (CBAR), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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, including the CNS, possess the ability of converting cholesterol into bioactive steroids. For example, astrocytes and neurons can convert cholesterol into testosterone, estrone (E1), estradiol (E2), dehydroepiandrosterone (DHEA), androstenedione (4D), and

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M Jensterle Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia

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A Podbregar University Rehabilitation Institute Republic of Slovenia, Ljubljana, Slovenia

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K Goricar University of Ljubljana, Faculty of Medicine, Institute of Biochemistry, Pharmacogenetics Laboratory, Ljubljana, Slovenia

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N Gregoric Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia

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A Janez Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia

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) should be recommended as the first-line approach ( 2 , 3 ), yet in clinical practice LSM often fails. On the other hand, testosterone replacement therapy (TRT) appears to improve body composition and glycometabolic profile without clearly affecting

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Thomas Reinehr Department of Pediatric Endocrinology, Diabetes, and Nutrition Medicine, Vestische Hospital for Children and Adolescents, University of Witten/Herdecke, Datteln, Germany

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Alexandra Kulle Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University Hospital of Schleswig – Holstein, UKSH, Campus Kiel/Christian Albrechts University of Kiel, CAU, Kiel, Germany

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Juliane Rothermel Department of Pediatric Endocrinology, Diabetes, and Nutrition Medicine, Vestische Hospital for Children and Adolescents, University of Witten/Herdecke, Datteln, Germany

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Caroline Knop-Schmenn Department of Pediatric Endocrinology, Diabetes, and Nutrition Medicine, Vestische Hospital for Children and Adolescents, University of Witten/Herdecke, Datteln, Germany

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Nina Lass Department of Pediatric Endocrinology, Diabetes, and Nutrition Medicine, Vestische Hospital for Children and Adolescents, University of Witten/Herdecke, Datteln, Germany

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Christina Bosse Department of Pediatric Endocrinology, Diabetes, and Nutrition Medicine, Vestische Hospital for Children and Adolescents, University of Witten/Herdecke, Datteln, Germany

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Paul-Martin Holterhus Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University Hospital of Schleswig – Holstein, UKSH, Campus Kiel/Christian Albrechts University of Kiel, CAU, Kiel, Germany

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, 21-deoxycorticosterone, deoxycorticosterone, corticosterone, 11-deoxycortisol, cortisol, cortisone, androstenedione, testosterone, dehydroepiandrostenedione sulfate (DHEA-S), estrone (E1), estradiol (E2), luteinizing hormone (LH), follicle

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Tristan Avril Pediatric Endocrinology Department, CHU Bicetre, Assistance Publique-Hôpitaux de Paris, Reference Center for Rare Disease CRMR DevGen, Le Kremlin Bicêtre, Paris, France

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Quentin Hennocq Datascience platform, Imagine Institute, Université Paris Cité, Paris, France

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Anne-Sophie Lambert Pediatric Endocrinology Department, CHU Bicetre, Assistance Publique-Hôpitaux de Paris, Reference Center for Rare Disease CRMR DevGen, Le Kremlin Bicêtre, Paris, France

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Juliane Leger Pediatric Endocrinology Department, CHU Robert Debré, Assistance Publique-Hôpitaux de Paris, Reference Center for Rare Disease CRMR de la Croissance et du Développement, Paris, France
Université Paris Cité, Faculté de Santé, UFR de Médecine, Paris, France

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Dominique Simon Pediatric Endocrinology Department, CHU Robert Debré, Assistance Publique-Hôpitaux de Paris, Reference Center for Rare Disease CRMR de la Croissance et du Développement, Paris, France

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Laetitia Martinerie Pediatric Endocrinology Department, CHU Robert Debré, Assistance Publique-Hôpitaux de Paris, Reference Center for Rare Disease CRMR de la Croissance et du Développement, Paris, France
Université Paris Cité, Faculté de Santé, UFR de Médecine, Paris, France
Inserm UMR1185, Le Kremlin Bicetre, Paris, France

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Claire Bouvattier Pediatric Endocrinology Department, CHU Bicetre, Assistance Publique-Hôpitaux de Paris, Reference Center for Rare Disease CRMR DevGen, Le Kremlin Bicêtre, Paris, France
Inserm UMR1185, Le Kremlin Bicetre, Paris, France
Paris-Saclay University, Paris, France

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cells, and perhaps, by extension, for future fertility ( 3 , 4 , 5 , 6 ). Anti-Müllerian hormone (AMH) and Inhibin B are reliable biomarkers reflecting Sertoli cells function, while testosterone is an index of Leydig cell activation. Boys with CHH

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