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Milou Cecilia Madsen Department of Internal Medicine and Center of Expertise on Gender Dysphoria, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands

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Martin den Heijer Department of Internal Medicine and Center of Expertise on Gender Dysphoria, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands

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Claudia Pees Walaeus Library, Leiden University Medical Center, Leiden, the Netherlands

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Nienke R Biermasz Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands

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Leontine E H Bakker Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands

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testosterone-dependent group are transgender people looking for masculinization. These people are birth-assigned female but identify as male or non-binary. To induce virilization, testosterone therapy is prescribed. This includes deepening of the voice

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Peter Bond P Bond, Department of Internal Medicine, Elisabeth TweeSteden Hospital, Tilburg, Netherlands

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Tijs Verdegaal T Verdegaal, Department of Internal Medicine, Spaarne Gasthuis, Haarlem, Netherlands

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Diederik L Smit D Smit, Department of Internal Medicine, Elisabeth TweeSteden Hospital, Tilburg, Netherlands

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Erythrocytosis, or elevated hematocrit, is a common side effect of testosterone therapy (TTh) in male hypogonadism. Testosterone stimulates erythropoiesis through an initial rise in erythropoietin (EPO), establishment of a new EPO/hemoglobin ‘set point’, and a parallel decrease in the master iron regulator protein hepcidin, as well as several other potential mechanisms. Evidence shows an increased thrombotic risk associated with TTh–induced erythrocytosis. Several guidelines for the treatment of male hypogonadism by endocrine organizations recommend against starting TTh in patients presenting with elevated hematocrit at baseline or to stop TTh when its levels cannot be controlled by dose-adjustments. Importantly, therapeutic phlebotomy or venesection is mentioned as a means of reducing hematocrit in these patients. However, evidence supporting the efficacy or safety of therapeutic phlebotomy in lowering hematocrit in TTh–induced erythrocytosis is lacking. In light of this dearth of evidence, the recommendation to lower hematocrit using therapeutic phlebotomy is notable, as phlebotomy lowers tissue oxygen partial pressure (pO2) and, eventually, depletes iron stores, thereby triggering various biological pathways which might also increase thrombotic risk. The potential pros and cons should therefore be carefully weighed against each other and shared decision making is recommended for initiating therapeutic phlebotomy as a treatment in patients on TTh who present with increased hematocrit.

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Mette Bøgehave Department of Clinical Biochemistry, Hospital South West Jutland, University Hospital of Southern Denmark, Esbjerg, Denmark
Unit for Thrombosis Research, Department of Regional Health Research, University of Southern Denmark, Denmark

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Dorte Glintborg Department of Endocrinology, Odense University Hospital, Odense, Denmark
Department of Clinical Research, University of Southern Denmark, Odense, Denmark
OPEN, Open Patient data Explorative Network, Odense University Hospital, Region of Southern Denmark, Odense, Denmark

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Jørgen Brodersen Gram Department of Clinical Biochemistry, Hospital South West Jutland, University Hospital of Southern Denmark, Esbjerg, Denmark
Unit for Thrombosis Research, Department of Regional Health Research, University of Southern Denmark, Denmark

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Else-Marie Bladbjerg Department of Clinical Biochemistry, Hospital South West Jutland, University Hospital of Southern Denmark, Esbjerg, Denmark
Unit for Thrombosis Research, Department of Regional Health Research, University of Southern Denmark, Denmark

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Marianne Skovsager Andersen Department of Endocrinology, Odense University Hospital, Odense, Denmark
Department of Clinical Research, University of Southern Denmark, Odense, Denmark

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Johannes Jakobsen Sidelmann Department of Clinical Biochemistry, Hospital South West Jutland, University Hospital of Southern Denmark, Esbjerg, Denmark
Unit for Thrombosis Research, Department of Regional Health Research, University of Southern Denmark, Denmark

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significantly different from the placebo group. Corresponding to our findings, previous studies report a reduction in protein C ( 23 ), an increase in free protein S ( 26 ), and no effect on TFPI and antithrombin ( 20 , 22 ) after testosterone therapy. The

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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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A . Evaluation of 451 Danish boys with delayed puberty: diagnostic use of a new puberty nomogram and effects of oral testosterone therapy . Journal of Clinical Endocrinology and Metabolism 2015 100 1376 – 1385 . ( https://doi.org/10.1210/jc.2014

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Sakina Kherra CHU Parnet Hopital, Algiers, Algeria

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Wendy Forsyth Paterson Royal Hospital for Sick Children, Yorkhill, Glasgow, UK

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Filiz Mine Cizmecioglu Paediatric Endocrinology and Diabetes Department, Kocaeli University, Kocaeli, Turkey

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Jeremy Huw Jones Department of Pediatric Endocrinology, Royal Hospital for Children Glasgow, NHS Greater Glasgow and Clyde, Glasgow, UK

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Mariam Kourime Abderrahim Harouchi Hôpital, Casablanca, Morocco

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Heba Hassan Elsedfy Pediatrics Department, Ain Shams University, Cairo, Egypt

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Sameh Tawfik Department of Pediatrics, Maadi Hospital, Cairo, Egypt

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Andreas Kyriakou Department of Pediatric Endocrinology, Royal Hospital for Children Glasgow, NHS Greater Glasgow and Clyde, Glasgow, UK

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Mohamad Guftar Shaikh Department of Pediatric Endocrinology, Royal Hospital for Children Glasgow, NHS Greater Glasgow and Clyde, Glasgow, UK

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Malcolm David Cairns Donaldson Section of Child Health, Glasgow University School of Medicine, Glasgow, UK

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point per patient per age band. Median (range) values are shown. Testosterone values post hCG given to 16/19 patients prior to surgery and to 9 patients to test Leydig cell reserve are shown. Data does not include patients on testosterone therapy

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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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engagement, age of diagnosis, testosterone therapy and physical and mental health status, and to compare values to a European Social Surveys (ESS) reference population. Methods Study population This study was part of the European dsd-LIFE study, a

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Mikkel Andreassen Department of Endocrinology, Faculty of Health Science, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Anders Juul Department of Growth and Reproduction, Faculty of Health Science, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Ulla Feldt-Rasmussen Department of Endocrinology, Faculty of Health Science, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Niels Jørgensen Department of Growth and Reproduction, Faculty of Health Science, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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with pituitary diseases were offered cryopreservation of semen for future fertility treatment before testosterone therapy was initiated, or in selected younger cases before pituitary surgery or radiation therapy. All patients who started testosterone

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Agnieszka Pazderska Department of Endocrinology, Newcastle-upon-Tyne Hospitals, Newcastle upon Tyne, UK
Department of Endocrinology, St James’s Hospital, Dublin, Ireland

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Yaasir Mamoojee Department of Endocrinology, Newcastle-upon-Tyne Hospitals, Newcastle upon Tyne, UK

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Satish Artham Department of Endocrinology, Newcastle-upon-Tyne Hospitals, Newcastle upon Tyne, UK

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Margaret Miller Department of Endocrinology, Newcastle-upon-Tyne Hospitals, Newcastle upon Tyne, UK

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Stephen G Ball Department of Endocrinology, Central Manchester University Hospitals, Manchester, UK
Department of Endocrinology, University of Manchester, Manchester, UK

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Tim Cheetham Endocrine Research Group, Institute of Genetic Medicine, University of Newcastle-upon-Tyne, Newcastle upon Tyne, UK
Department of Paediatric Endocrinology & Diabetes, Newcastle-upon-Tyne Hospitals, Newcastle upon Tyne, UK

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Richard Quinton Department of Endocrinology, Newcastle-upon-Tyne Hospitals, Newcastle upon Tyne, UK
Endocrine Research Group, Institute of Genetic Medicine, University of Newcastle-upon-Tyne, Newcastle upon Tyne, UK

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remainder being identifiable later during the process of pubertal induction through failure to normalise testicular volume with testosterone therapy ( 1 ). Given the aforementioned factors, the diagnostic evaluation and management of pubertal delay should

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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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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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are gradually being phased out because of the increased risk of thrombosis ( 4 ). Oestradiol implants are not widely available in the United Kingdom. Commonly available option for testosterone therapy in the United Kingdom includes 2% transdermal gel

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