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Natacha Driessens Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, Department of Endocrinology, Route de Lennik, Brussels, Belgium

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Madhu Prasai Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, Department of Endocrinology, Route de Lennik, Brussels, Belgium

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Orsalia Alexopoulou Department of Endocrinology, Cliniques Universitaires Saint Luc, Brussels, Belgium

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Christophe De Block Department of Endocrinology-Diabetology-Metabolism, Universitair Ziekenhuis Antwerpen & University of Antwerp, Drie Eikenstraat, Edegem, Belgium

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Eva Van Caenegem Department of Endocrinology, Academisch Ziekenhuis Sint-Jan Brugge – Oostende AV, Ruddershove, Brugge, Belgium

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Guy T’Sjoen Department of Endocrinology, Ghent Universitary Hospital, C. Heymanslaan, Gent, Belgium

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Frank Nobels Department of Endocrinology, Onze-Lieve Vrouw Ziekenhuis, Moorselbaan, Aalst, Belgium

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Christophe Ghys Department of Endocrinology, Universitair Ziekenhuis Brussel, Laarbeeklaan, Brussels, Belgium

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Laurent Vroonen Department of Endocrinology, Cliniques Universitaires de Liège, Avenue de l’hôpital, Liège, Belgium

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Corinne Jonas Department of Endocrinology, CHU UCL Namur - Godinne, Avenue Docteur Gaston Thérasse, Yvoir, Belgium

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Bernard Corvilain Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, Department of Endocrinology, Route de Lennik, Brussels, Belgium

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Dominique Maiter Department of Endocrinology, Cliniques Universitaires Saint Luc, Brussels, Belgium

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countries ( 1 ) and the lowest in Japan. Despite the advent of glucocorticoid replacement therapy in the early 1950s, life expectancy remains lower than in the general population ( 2 ), with increased morbidity and impaired quality of life ( 3 , 4

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Angela Köninger Department of Gynecology and Obstetrics, University of Duisburg-Essen, Essen, Germany

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Antonella Iannaccone Department of Gynecology and Obstetrics, University of Duisburg-Essen, Essen, Germany

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Ensar Hajder Department of Gynecology and Obstetrics, University of Duisburg-Essen, Essen, Germany

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Mirjam Frank Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg-Essen, Essen, Germany

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Boerge Schmidt Institute for Medical Informatics, Biometry and Epidemiology (IMIBE), University of Duisburg-Essen, Essen, Germany

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Ekkehard Schleussner Department of Obstetrics, Jena University Hospital, Jena, Germany

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Rainer Kimmig Department of Gynecology and Obstetrics, University of Duisburg-Essen, Essen, Germany

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Alexandra Gellhaus Department of Gynecology and Obstetrics, University of Duisburg-Essen, Essen, Germany

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Hans Dieplinger Division of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria

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duration of more than 3 months. Clinical or biochemical signs of hyperandrogenism were diagnosed with a Ferriman–Gallway score >7 ( 29 ) or obvious acne or alopecia ( 30 ) or an increased total testosterone (normal range 0.5–2.6 nmol/L) and/or DHEAS (normal

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Gamze Akkuş Division of Endocrinology, Internal Medicine and Endocrinology, Cukurova University Medical Faculty, Department of Internal Medicine, Adana, Turkey

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Isa Burak Güney Nuclear Medicine Department, Cukurova University Medical Faculty, Adana, Turkey

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Fesih Ok Urology Department, Cukurova University Medical Faculty, Adana, Turkey

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Mehtap Evran Division of Endocrinology, Internal Medicine and Endocrinology, Cukurova University Medical Faculty, Department of Internal Medicine, Adana, Turkey

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Volkan Izol Urology Department, Cukurova University Medical Faculty, Adana, Turkey

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Şeyda Erdoğan Pathology Department, Cukurova University Medical Faculty, Adana, Turkey

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Yıldırım Bayazıt Urology Department, Cukurova University Medical Faculty, Adana, Turkey

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Murat Sert Division of Endocrinology, Internal Medicine and Endocrinology, Cukurova University Medical Faculty, Department of Internal Medicine, Adana, Turkey

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Tamer Tetiker Division of Endocrinology, Internal Medicine and Endocrinology, Cukurova University Medical Faculty, Department of Internal Medicine, Adana, Turkey

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Introduction Since the early 1980s, the prevalence of adrenal masses have been increasing due to the frequent use of radiological imaging such as magnetic resonance imaging (MRI), computerized tomography (CT) in clinical practice. The

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Hong Tang Departments of Gynaecology and Obstetrics Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China

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Xiaomei Jiang Departments of Gynaecology and Obstetrics Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China

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Yu Hua Departments of Gynaecology and Obstetrics Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China

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Heyue Li Departments of Gynaecology and Obstetrics Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China

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Chunlan Zhu Departments of Gynaecology and Obstetrics Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China

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Xiaobai Hao Departments of Gynaecology and Obstetrics Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China

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Minhui Yi Departments of Gynaecology and Obstetrics Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China

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Linxia Li Departments of Gynaecology and Obstetrics Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China

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People’s Hospital (item number: 2021-AR-059). Adult female C57BL/6J mice were housed withaccess to food and water ad libitum . The PCOS mouse model was established as described previously ( 18 ). In brief, female C57BL/6J mice (4 weeks old) were

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Eric Seidel Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Nephrology and Medical Intensive Care, BCRT – Berlin Institute of Health Center for Regenerative Therapies, Berlin, Germany
Berlin Institute of Health (BIH), Berlin, Germany
Department of Nephrology, School of Medicine, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

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Gudrun Walenda Department of Nephrology, School of Medicine, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

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Clemens Messerschmidt Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
Core Unit Bioinformatics, Berlin Institute of Health, Berlin, Germany

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Benedikt Obermayer Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
Core Unit Bioinformatics, Berlin Institute of Health, Berlin, Germany

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Mirko Peitzsch Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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Paal Wallace Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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Rohini Bahethi Department of Nephrology, School of Medicine, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

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Taekyeong Yoo Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea

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Murim Choi Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea

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Petra Schrade Charité – Universitaetsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institut für Vegetative Anatomie, Berlin, Germany

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Sebastian Bachmann Charité – Universitaetsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institut für Vegetative Anatomie, Berlin, Germany

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Gerhard Liebisch Institute of Clinical Chemistry and Laboratory Medicine, Regensburg University Hospital, Regensburg, Germany

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Graeme Eisenhofer Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

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Dieter Beule Core Unit Bioinformatics, Berlin Institute of Health, Berlin, Germany
Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany

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Ute I Scholl Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Nephrology and Medical Intensive Care, BCRT – Berlin Institute of Health Center for Regenerative Therapies, Berlin, Germany
Berlin Institute of Health (BIH), Berlin, Germany
Department of Nephrology, School of Medicine, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

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last passage; N C , number of cells counted at the current passage; N S , number of cells seeded after the last passage. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay After discontinuation of mitotane treatment (if

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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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concentration of LH exceeds +2 s.d. . Standard treatment is either peroral testosterone undecanoate (TU) (Testosterone ‘Paranova’; (Paranova Danmark A/S, Herlev, Denmark)) or transdermal testosterone (Tostran 2%; Kyowa Kirin, Holland), with dose titration

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Paul-Martin Holterhus Department of Pediatrics I, Pediatric Endocrinology and Diabetology, University Hospital of Schleswig-Holstein, UKSH, Campus Kiel and Christian Albrechts University, CAU, Kiel, Germany

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Alexandra Kulle Department of Pediatrics I, Pediatric Endocrinology and Diabetology, University Hospital of Schleswig-Holstein, UKSH, Campus Kiel and Christian Albrechts University, CAU, Kiel, Germany

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Anne-Marie Till Department of Pediatrics, Pediatric Hematology and Oncology, University Hospital of Schleswig-Holstein, UKSH, Campus Lübeck, Germany

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Caroline Stille Department of Pediatrics, Pediatric Hematology and Oncology, University Hospital of Schleswig-Holstein, UKSH, Campus Lübeck, Germany

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Tabea Lamprecht Department of Pediatrics I, Pediatric Endocrinology and Diabetology, University Hospital of Schleswig-Holstein, UKSH, Campus Kiel and Christian Albrechts University, CAU, Kiel, Germany

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Simon Vieth Department of Pediatrics I, Pediatric Hematology and Oncology, University Hospital of Schleswig-Holstein, UKSH, Campus Kiel and Christian-Albrechts-University, CAU, Kiel, Germany

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Melchior Lauten Department of Pediatrics, Pediatric Hematology and Oncology, University Hospital of Schleswig-Holstein, UKSH, Campus Lübeck, Germany

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glucocorticoids and mineralocorticoids. The most important acquired example of global adrenal insufficiency is Addison’s disease ( 9 ). Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is a genetically determined block of

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Stine A Holmboe Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Blegdamsvej, Copenhagen, Denmark
The International Research Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Ravi Jasuja Research Program in Men’s Health: Aging and Metabolism, Brigham and Womens Hospital, Harvard Medical School, Boston, Massachusetts, USA

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Brian Lawney Research Program in Men’s Health: Aging and Metabolism, Brigham and Womens Hospital, Harvard Medical School, Boston, Massachusetts, USA

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

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Niels Joergensen Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Blegdamsvej, Copenhagen, Denmark
The International Research Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Allan Linneberg Centre for Clinical Research and Prevention, Frederiksberg Hospital, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Tina Kold Jensen Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Blegdamsvej, Copenhagen, Denmark
The International Research Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Denmark

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Niels Erik Skakkebæk Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Blegdamsvej, Copenhagen, Denmark
The International Research Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Anders Juul Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Blegdamsvej, Copenhagen, Denmark
The International Research Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Anna-Maria Andersson Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Blegdamsvej, Copenhagen, Denmark
The International Research Centre in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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emigration, after which they were censored. Statistical methods Mean, s.d. and relative s.d. (sample s.d. σ/sample mean µ × 100) were calculated for each of the three free testosterone variables. Initially, cFTV and cFTZ levels were visually

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Greta B Raglan Department of Psychology, American University, Washington, District of Columbia, USA

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Louis A Schmidt Department of Psychology, Neuroscience & Behavior, McMaster University, Hamilton, Ontario, Canada

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Jay Schulkin Department of Research, American College of Obstetricians and Gynecologists, Washington, District of Columbia, USA
Department of Neuroscience, Georgetown University, Washington, District of Columbia, USA

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lower-than-usual release of glucocorticoids in fearful situations, whereas others have higher release ( 2 ), and glucocorticoid release has differential effects and antecedents depending on an individual’s history and development ( 3 , 4 ). The roles of

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L Ghataore Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK

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I Chakraborti Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK

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S J Aylwin Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK

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K-M Schulte Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK

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D Dworakowska Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK
Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK

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P Coskeran Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK

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N F Taylor Departments of, Clinical Biochemistry, Medicine, Department of Endocrinology and Internal Medicine, King's College Hospital, London SE5 9RS, UK

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, the 20β-reduced epimer was much diminished, as expected. Other major markers showed unchanged metabolism. These were (manuscript in preparation) pregnanediol (20α), pregnanetriol (20α), DHEA, DHEA metabolites, tetrahydro-11-deoxycortisol (5β) and 5

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