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Martin Zweifel Department of Medical Oncology, University Hospital Bern, Bern, Switzerland

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Cristiana Sessa Istituto Oncologico della Svizzera Italiana, Bellinzona, Switzerland

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for the Swiss Group for Clinical Cancer Research (SAKK)
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Introduction For the treatment of breast cancer (BC), testosterone was already used extensively between the 1930s and 1960s with anecdotal tumour responses (especially in bone metastases) seen in up to 20% of treated women ( 1 , 2 , 3 , 4

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Ahmet Uçar
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Nurçin Saka
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Firdevs Baş
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Nihal Hatipoğlu Pediatric Endocrine Unit, Pediatric Endocrine Unit, Istanbul Medical Faculty, Istanbul University, 34093 Fatih, Istanbul, Turkey

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Rüveyde Bundak
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Feyza Darendeliler
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blood samples for glucose and lipids (total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and triglycerides (TGs)), serum insulin, LH, FSH, DHEAS, total testosterone, and high-sensitivity C

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T S Nilsen Department of Physical Performance, Norwegian School of Sports Sciences, Oslo, Norway

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L Thorsen Department of Oncology, Oslo University Hospital, Oslo, Norway

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C Kirkegaard Department of Physical Performance, Norwegian School of Sports Sciences, Oslo, Norway

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I Ugelstad Department of Physical Performance, Norwegian School of Sports Sciences, Oslo, Norway

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S D Fosså Department of Oncology, Oslo University Hospital, Oslo, Norway

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T Raastad Department of Physical Performance, Norwegian School of Sports Sciences, Oslo, Norway

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E3 ligases promote ubiquitin conjugation of proteins destined for breakdown by the 26s proteasome ( 10 ). Removal of testosterone has been shown to increase the expression of muscle-specific E3 ligases ( 11 ), and this may also play a role in ADT

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Muriel Houang Laboratoire des Explorations Fonctionnelles Endocriniennes, Hôpital Armand Trousseau, AP-HP Sorbonne Université, Paris, France

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Thao Nguyen-Khoa Centre Régional de Dépistage Néonatal-Ile de France, Hôpital Necker-Enfants Malades, AP-HP Centre Université de Paris, Paris, France

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Thibaut Eguether Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, Paris, France
Département de Métabolomique Clinique, Hôpital Saint-Antoine, AP-HP Sorbonne Université, Paris, France

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Bettina Ribault Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, Paris, France
Département de Métabolomique Clinique, Hôpital Saint-Antoine, AP-HP Sorbonne Université, Paris, France

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Séverine Brabant Laboratoire d’Explorations Fonctionnelles, Hôpital Necker-Enfants Malades, AP-HP Centre Université de Paris, Paris, France

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Michel Polak Centre Régional de Dépistage Néonatal-Ile de France, Hôpital Necker-Enfants Malades, AP-HP Centre Université de Paris, Paris, France
Université de Paris, INSERM, Institut IMAGINE, Hôpital Necker-Enfants Malades, AP-HP, Paris, France

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Irène Netchine Laboratoire des Explorations Fonctionnelles Endocriniennes, Hôpital Armand Trousseau, AP-HP Sorbonne Université, Paris, France
Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, Paris, France
Hôpital Armand Trousseau, AP-HP Sorbonne Université, Paris, France

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Antonin Lamazière Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, Paris, France
Département de Métabolomique Clinique, Hôpital Saint-Antoine, AP-HP Sorbonne Université, Paris, France

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, a mixture of the deuterated internal standard (IS) (150 µL containing 17-OHP-d8, testosterone-d4, D4-androstenedione (D4A)-d5, and 21-deoxycortisol (21-DF)-d8)) was added to 150 µL of serum. The solution was mixed and left standing for 5 min, and

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Richard J Auchus Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA
Veterans Affairs Medical Center, Ann Arbor, Michigan, USA

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with the recommendations of professional societies, and the guidance of the United States Food and Drug Administration. The AACE position statement systematically reviews the patterns of misuse for testosterone, growth hormone (rhGH), thyroxine and

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Elena Galazzi IRCSS Istituto Auxologico Italiano, Laboratory of Endocrine and Metabolic Research and Division of Endocrine and Metabolic Diseases, Milan, Italy
Department of Clinical Sciences and Community Health, Università degli Studi, Milan, Italy

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Paolo Duminuco IRCSS Istituto Auxologico Italiano, Laboratory of Endocrine and Metabolic Research and Division of Endocrine and Metabolic Diseases, Milan, Italy

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Mirella Moro IRCSS Istituto Auxologico Italiano, Laboratory of Endocrine and Metabolic Research and Division of Endocrine and Metabolic Diseases, Milan, Italy

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Fabiana Guizzardi IRCSS Istituto Auxologico Italiano, Laboratory of Endocrine and Metabolic Research and Division of Endocrine and Metabolic Diseases, Milan, Italy

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Nicoletta Marazzi IRCSS Istituto Auxologico Italiano, Laboratory for Auxo-Endocrinological Research, Milan, Italy

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Alessandro Sartorio IRCSS Istituto Auxologico Italiano, Laboratory for Auxo-Endocrinological Research, Milan, Italy
Division of Auxology and Metabolic Diseases, IRCSS Istituto Auxologico Italiano, Piancavallo (VB), Italy

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Sabrina Avignone Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, U.O.C Neuroradiologia, Milan, Italy

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Marco Bonomi IRCSS Istituto Auxologico Italiano, Laboratory of Endocrine and Metabolic Research and Division of Endocrine and Metabolic Diseases, Milan, Italy
Department of Clinical Sciences and Community Health, Università degli Studi, Milan, Italy

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Luca Persani IRCSS Istituto Auxologico Italiano, Laboratory of Endocrine and Metabolic Research and Division of Endocrine and Metabolic Diseases, Milan, Italy
Department of Clinical Sciences and Community Health, Università degli Studi, Milan, Italy

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Maria Teresa Bonati IRCCS Istituto Auxologico Italiano, Service of Medical Genetics, Milan, Italy

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inhibin B and undetectable total testosterone (TTe) levels ( Table 1 ). He was normosmic at Brief-Smell Identification test (B-SIT) and normal central olfactory structures were confirmed using MRI. His karyotype was 46,XY. At the age of 15 years, he

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Sebastião Freitas de Medeiros Department of Gynecology and Obstetrics, Medical School, Federal University of Mato Grosso, Cuiabá, Mato Grosso, Brazil
Tropical Institute of Reproductive Medicine, Cuiabá, Mato Grosso, Brazil

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Márcia Marly Winck Yamamoto Tropical Institute of Reproductive Medicine, Cuiabá, Mato Grosso, Brazil

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Matheus Antônio Souto de Medeiros Tropical Institute of Reproductive Medicine, Cuiabá, Mato Grosso, Brazil

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Bruna Barcelo Barbosa Tropical Institute of Reproductive Medicine, Cuiabá, Mato Grosso, Brazil

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José Maria Soares Junior Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Edmund Chada Baracat Disciplina de Ginecologia, Departamento de Obstetrícia e Ginecologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo, Brazil

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, 33 ). Biochemical hyperandrogenism was defined by at least one of the following criteria: total testosterone ≥2.1 nmol/L, free testosterone (FT)≥0.03 pmol/L, dehydroepiandrosterone sulfate (DHEAS) ≥6.7 µmol/L, androstenedione (A4) ≥8.6 nmol/L, and

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Zofia Kolesinska Department of Pediatric Endocrinology and Rheumatology, Poznan University of Medical Sciences, Poznan, Poland

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James Acierno Jr Endocrinology, Diabetology & Metabolism Service, Lausanne University Hospital, Lausanne, Switzerland

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S Faisal Ahmed Developmental Endocrinology Research Group, School of Medicine, Dentistry & Nursing, University of Glasgow, Glasgow, UK

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Cheng Xu Endocrinology, Diabetology & Metabolism Service, Lausanne University Hospital, Lausanne, Switzerland

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Karina Kapczuk Division of Gynecology, Department of Perinatology and Gynecology, Poznan University of Medical Sciences, Poznan, Poland

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Anna Skorczyk-Werner Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland

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Hanna Mikos Department of Pediatric Endocrinology and Rheumatology, Poznan University of Medical Sciences, Poznan, Poland

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Aleksandra Rojek Department of Pediatric Endocrinology and Rheumatology, Poznan University of Medical Sciences, Poznan, Poland

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Andreas Massouras Saphetor, SA, Lausanne, Switzerland

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Maciej R Krawczynski Department of Medical Genetics, Poznan University of Medical Sciences, Poznan, Poland

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Nelly Pitteloud Endocrinology, Diabetology & Metabolism Service, Lausanne University Hospital, Lausanne, Switzerland

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Marek Niedziela Department of Pediatric Endocrinology and Rheumatology, Poznan University of Medical Sciences, Poznan, Poland

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testosterone were measured by radioimmunoassays: Active Androstenedione RIA (Beckman Coulter, Immunotech) and TESTO-RIA-CT (DIAsource ImmunoAssays S.A., Belgium), respectively. Anti-Müllerian hormone (AMH) and inhibin B were evaluated by ELx800 Absorbance

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Estelle Bonnet Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service d’endocrinologie pédiatrique, Bron, France

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Mathias Winter Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Hospices Civils de Lyon, Bron, France
Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service de psychopathologie du développement, Bron, France
Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Centre de biologie et pathologie Est, Service d’hormonologie, d’endocrinologie moléculaire et des maladies rares, Bron, France

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Delphine Mallet Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Hospices Civils de Lyon, Bron, France
Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Centre de biologie et pathologie Est, Service d’hormonologie, d’endocrinologie moléculaire et des maladies rares, Bron, France

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Ingrid Plotton Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Hospices Civils de Lyon, Bron, France
Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service Endocrinologie Moléculaire et Maladies Rares, Bron, France

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Claire Bouvattier Centre Hospitalier Universitaire AP-HP, Hôpital Bicêtre, Service d’endocrinologie pédiatrique Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN Université Paris Saclay, Le Kremlin-Bicêtre, France

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Maryse Cartigny Centre Hospitalier Régional Universitaire Lille, Hôpital Jeanne de Flandre, Unité d’Endocrinologie pédiatrique Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Lille, France

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Laetiti Martinerie Centre Hospitalier Universitaire AP-HP, Hôpital Robert Debré, Service d’Endocrinologie pédiatrique Centre de Référence des Maladies Rares Endocriniennes de la Croissance et du Développement – CRMERC Université de Paris, Paris, France

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Michel Polak Centre Hospitalier Universitaire AP-HP, Hôpital universitaire Necker Enfants malades, Endocrinologie gynécologie diabétologie pédiatriques Centre de référence des maladies endocriniennes rares de la croissance et du développement Inserm U1016, institut Imagine, Paris, France

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Anne Bachelot Centre Hospitalier Universitaire AP-HP, Hôpital Pitié Salpêtrière, Department of Endocrinology and Reproductive Medicine Centre de Référence des Maladies Endocriniennes Rares de la Croissance et du Développement Centre de Référence des pathologies gynécologiques rares IE3M, Paris, France

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Frédéric Huet Centre Hospitalier Universitaire Dijon-Bourgogne, Hôpital d’Enfants, Service de Pédiatrie Multidisciplinaire, Dijon, France

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Sabine Baron Centre Hospitalier universitaire de Nantes, Hôpital Mère-Enfant, Service de Pédiatrie, Nantes, France

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Muriel Houang Centre Hospitalier Universitaire AP-HP, Hôpital Armand Trousseau, Service d'Explorations Fonctionnelles Endocriniennes, Paris, France

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Sylvie Soskin Hôpitaux Universitaires de Strasbourg, CHU Hautepierre, Service de Pédiatrie 1, Strasbourg, France

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Anne Lienhardt Centre hospitalier universitaire Limoges, Hôpital de la Mère et de l’enfant, Service de Pédiatrie, Limoges, France

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Jérôme Bertherat Groupement Hospitalier Universitaire de Paris, AP-HP, Hôpital Cochin, Service d'Endocrinologie, Paris, France

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Cyril Amouroux Centre Hospitalier Universitaire de Montpellier, Hôpital Lapeyronie, Service de Néphrologie et Endocrinologie Pédiatrique Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Montpellier, France

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Aurore Bouty Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Hospices Civils de Lyon, Bron, France
Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service de chirurgie Uro-viscérale et de Transplantation de l’Enfant, Bron, France

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Lise Duranteau AP-HP, Hôpital Bicêtre, Unité de gynécologie de l’adolescente Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN Université Paris Saclay, Le Kremlin-Bicêtre, France

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Rémi Besson Centre Hospitalier Régional Universitaire Lille, Hôpital Jeanne de Flandre, Service de chirurgie pédiatrique Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Lille, France

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Alaa El Ghoneimi Centre Hospitalier Universitaire AP-HP Robert Debré, Service de Chirurgie Viscérale et Urologie pédiatrique Centre de Référence des Maladies Endocriniennes de la croissance et du développement – CRMERC Université de Paris, Paris, France

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Dinane Samara-Boustani Centre Hospitalier Universitaire AP-HP, Hôpital Necker Enfants malades, Endocrinologie gynécologie diabétologie pédiatriques Centre de référence des maladies endocriniennes rares de la croissance et du développement, Paris, France

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François Becmeur Hospitaux Universitaires de Strasbourg, CHU Hautepierre, Service de chirurgie pédiatrique, Strasbourg, France

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Nicolas Kalfa Centre Hospitalier Universitaire de Montpellier, Hôpital Lapeyronie, Service de Chirurgie Viscérale et Urologie Pédiatrique Centre National de Référence Maladies Rares du Développement Génital Constitutif Sud Institut Debrest de Santé Publique IDESP, UMR INSERM, Université de Montpellier, Montpellier, France

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Françoise Paris Centre Hospitalier Universitaire de Montpellier, Hôpital Lapeyronie, Service de Néphrologie et Endocrinologie Pédiatrique Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Montpellier, France

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François Medjkane Centre Hospitalier Régional Universitaire Lille, Hôpital Jeanne de Flandre, Service de psychiatrie de l’enfant et de l’adolescent Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Lille, France

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Aude Brac de la Perrière Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Hospices Civils de Lyon, Bron, France
Hospices Civils de Lyon, Groupement Hospitalier Est, Service d’endocrinologie, Bron, France

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Patricia Bretones Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service d’endocrinologie pédiatrique, Bron, France
Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Hospices Civils de Lyon, Bron, France

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Hervé Lejeune Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service de médecine de la reproduction, Bron, France
Université Claude Bernard, Lyon, France

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Marc Nicolino Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service d’endocrinologie pédiatrique, Bron, France
Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Hospices Civils de Lyon, Bron, France
Université Claude Bernard, Lyon, France

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Pierre Mouriquand Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Hospices Civils de Lyon, Bron, France
Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service de chirurgie Uro-viscérale et de Transplantation de l’Enfant, Bron, France
Université Claude Bernard, Lyon, France

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Daniela-Brindusa Gorduza Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Hospices Civils de Lyon, Bron, France
Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service de chirurgie Uro-viscérale et de Transplantation de l’Enfant, Bron, France

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Claire-Lise Gay Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service d’endocrinologie pédiatrique, Bron, France
Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Hospices Civils de Lyon, Bron, France

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determination of the testosterone/DHT ratio (elevated at baseline and/or after human chorionic gonadotrophin (hCG) stimulation test in SRD5A2 deficiency) and of the testosterone/androstenedione ratio (low at baseline and after hCG stimulation test in HSD17B3

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Shilpa Lingaiah Department of Obstetrics and Gynaecology, PEDEGO Research Unit, Medical Research Centre, University of Oulu and Oulu University Hospital, Oulu, Finland

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Laure Morin-Papunen Department of Obstetrics and Gynaecology, PEDEGO Research Unit, Medical Research Centre, University of Oulu and Oulu University Hospital, Oulu, Finland

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Terhi Piltonen Department of Obstetrics and Gynaecology, PEDEGO Research Unit, Medical Research Centre, University of Oulu and Oulu University Hospital, Oulu, Finland

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Inger Sundström-Poromaa Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden

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Elisabet Stener-Victorin Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

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Juha S Tapanainen Department of Obstetrics and Gynaecology, PEDEGO Research Unit, Medical Research Centre, University of Oulu and Oulu University Hospital, Oulu, Finland
Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

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/ASRM) consensus definition ( 25 ). Ovarian morphology was assessed by means of transvaginal ultrasonography in all subjects. Biochemical hyperandrogenism was defined as serum testosterone ≥2.3 nmol/L, according to the upper limits of the accredited laboratory at

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