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Rafaella Sales de Freitas Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil

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Thiago F A França Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil

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Sabine Pompeia Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil

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such as DHEA and its main metabolite, DHEA sulphate (DHEA-S) ( 15 , 23 ). As this brief overview of the literature shows, the role of peripheral kisspeptin concentrations and pubertal development still needs much clarification. In humans, kisspeptin

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Anna C van der Burgh Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Samer R Khan Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Sebastian J C M M Neggers Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands

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Ewout J Hoorn Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands

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Layal Chaker Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands

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, mean ± SD or median (IQR) Total, n * Type of testosterone status measurement Measurement method Testosterone or DHEA-S, mean ± SD or median (IQR) Amiri M, Andrology , 2019 Adult men from district-13 of Tehran, Iran 1999–2001 42

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

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

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

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, the LMS method accounts for local skewness (L), mean (M), and coefficient of variation (S) to establish continuous normal distributions with age ( 10 ). Supervised machine learning (ML) is an artificial intelligence method that is used for optimizing

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Elinor Chelsom Vogt Department of Clinical Science, University of Bergen, Bergen, Norway
K.G. Jebsen Center for Autoimmune Disorders, University of Bergen, Bergen, Norway
Department of Medicine, Haukeland University Hospital, Bergen, Norway

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Francisco Gómez Real Department of Clinical Science, University of Bergen, Bergen, Norway
Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway

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Eystein Sverre Husebye Department of Clinical Science, University of Bergen, Bergen, Norway
K.G. Jebsen Center for Autoimmune Disorders, University of Bergen, Bergen, Norway
Department of Medicine, Haukeland University Hospital, Bergen, Norway

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Sigridur Björnsdottir Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden

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Bryndis Benediktsdottir Medical Faculty, University of Iceland, Reykjavik, Iceland
Department of Sleep, Landspitali University Hospital Reykjavík, Reykjavik, Iceland

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Randi Jacobsen Bertelsen Department of Clinical Science, University of Bergen, Bergen, Norway

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Pascal Demoly University Hospital of Montpellier, IDESP, Univ Montpellier-Inserm, Montpellier, France

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Karl Anders Franklin Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå, Sweden

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Leire Sainz de Aja Gallastegui Unit of Epidemiology and Public Health, Department of Health, Basque Government, Vitoria-Gasteiz, Spain

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Francisco Javier Callejas González Department of Respiratory Medicine, Albacete University Hospital, Albacete, Spain

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Joachim Heinrich Institute and Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMU Munich, Munich, Germany
Allergy and Lung Health Unit, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia

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Mathias Holm Occupational and Environmental Medicine, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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Nils Oscar Jogi Department of Clinical Science, University of Bergen, Bergen, Norway

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Benedicte Leynaert Université Paris-Saclay, Inserm U1018, Center for Epidemiology and Population Health, Integrative Respiratory Epidemiology Team, Villejuif, France

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Eva Lindberg Department of Medical Sciences, Respiratory, Allergy and Sleep Medicine, Uppsala University, Uppsala, Sweden

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Andrei Malinovschi Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden

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Jesús Martínez-Moratalla Pneumology Service of the General University Hospital of Albacete, Albacete, Spain
Albacete Faculty of Medicine, Castilla-La Mancha University, Albacete, Spain

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Raúl Godoy Mayoral Department of Respiratory Medicine, Albacete University Hospital, Albacete, Spain

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Anna Oudin Section of Sustainable Health, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

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Antonio Pereira-Vega Juan Ramón Jiménez University Hospital in Huelva, Huelva, Spain

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Chantal Raherison Semjen INSERM, EpiCene Team U1219, University of Bordeaux, Talence, France

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Vivi Schlünssen Department of Public Health, Environment, Work and Health, Danish Ramazzini Centre, Aarhus University, Aarhus, Denmark
The National Research Center for the Working Environment, Copenhagen, Denmark

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Kai Triebner Department of Clinical Science, University of Bergen, Bergen, Norway

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Marianne Øksnes Department of Clinical Science, University of Bergen, Bergen, Norway
K.G. Jebsen Center for Autoimmune Disorders, University of Bergen, Bergen, Norway
Department of Medicine, Haukeland University Hospital, Bergen, Norway

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did not use HRT. FSH and luteinizing hormone (LH), were analyzed using ELISAs (Demeditec Diagnostics, Kiel, Germany), and the steroid hormones (17β-estradiol, estrone, progesterone, testosterone and DHEA-S) were measured using liquid chromatography

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Małgorzata Kałużna Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland

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Pola Kompf Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland

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Katarzyna Wachowiak-Ochmańska Heliodor Święcicki Clinical Hospital, Poznan, Poland

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Jerzy Moczko Department of Computer Science and Statistics, Poznan University of Medical Sciences, Poznan, Poland

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Aleksandra Królczyk Chair and Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland

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Adam Janicki Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland

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Karol Szapel Department of Physiotherapy, Poznan University of Medical Sciences, Poznan, Poland

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Marian Grzymisławski Chair and Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland

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Marek Ruchała Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland

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Katarzyna Ziemnicka Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland

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-stimulating hormone (FSH), luteinizing hormone (LH), DHEA sulfate (DHEAS), estradiol (E2), total testosterone (T), sex hormone-binding globulin (SHBG), anti-Müllerian hormone (AMH) and thyroid-stimulating hormone (TSH) measurements were performed using a Cobas 6000

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Srdjan Pandurevic Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy

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Ilaria Mancini Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy
Unit of Gynecology and Obstetrics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy

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Dimitri Mitselman Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy

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Matteo Magagnoli Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy

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Rita Teglia Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy

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Roberta Fazzeri Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy

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Paola Dionese Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy

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Carolina Cecchetti Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy

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Massimiliamo Caprio Department of Human Sciences and Quality of Life Promotion, San Raffaele Roma Open University, Rome, Italy
Laboratory of Cardiovascular Endocrinology, IRCCS San Raffaele, Rome, Italy

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Costanzo Moretti Department of Systems Medicine, Unit of Endocrinology, University of Rome Tor Vergata, Rome, Italy

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Justyna Sicinska Dermatology Clinic of CSK MSWiA Hospital, Warsaw, Poland

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Alessandro Agostini Department of Experimental, Diagnostic, and Specialty Medicine, University of Bologna, Bologna, Italy

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Domenica Gazineo Teaching Hospital, S. Orsola Hospital, Bologna, Italy

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Lea Godino Teaching Hospital, S. Orsola Hospital, Bologna, Italy

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Ignacio Sajoux Epigenomics in Endocrinology and Nutrition Group, Instituto de Investigacion Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Spain
Medical Department Pronokal Group, Barcelona, Spain

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Flaminia Fanelli Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy

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Cristina M Meriggiola Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy
Unit of Gynecology and Obstetrics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy

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Uberto Pagotto Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy

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Alessandra Gambineri Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy

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was approved by the local Ethics Committee Area Vasta Emilia Centro-AVEC (26/2020/Sper/AOUBo) and preregistered at the ClinicalTrials.gov Protocol Registration and Results System of the U.S. National Library of Medicine (NCT04801173). Study

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Xiuhua Liao Center of Reproductive Medicine, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
Fujian Maternal-Fetal Clinical Medicine Research Center, Fuzhou, China
Fujian Key Laboratory of Prenatal Diagnosis and Birth Defect, Fuzhou, China

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Suqin Zhu Center of Reproductive Medicine, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China

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Shumin Qiu Center of Reproductive Medicine, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China

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Hua Cao Center of Reproductive Medicine, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China

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Wenwen Jiang Center of Reproductive Medicine, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China

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Huiling Xu Center of Reproductive Medicine, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China

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Yan Sun Center of Reproductive Medicine, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China

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Beihong Zheng Center of Reproductive Medicine, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
Fujian Maternal-Fetal Clinical Medicine Research Center, Fuzhou, China
Fujian Key Laboratory of Prenatal Diagnosis and Birth Defect, Fuzhou, China

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were randomly divided into two groups: the model group ( n  = 20) and the control group ( n  = 20). Mice in the model group received daily subcutaneous injections of 0.1 mL of 0.6 mg/kg DHEA (androgen hormone) (Solarbio, Beijing, ID0220) dissolved in

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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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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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Mohamed Hssaini Department of Pediatric Endocrinology, University Hospital Center Hassan II, Fez, Morocco
Laboratory of Biotechnology, Environment, Food, and Health, Faculty of Sciences Dhar El Mahraz, Sidi Mohammed Ben Abdellah University, Fez, Morocco

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Sana Abourazzak Department of Pediatric Endocrinology, University Hospital Center Hassan II, Fez, Morocco

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Ihsane El Otmani Laboratory of Health Sciences and Technologies, Higher Institute of Health Sciences, Hassan First University of Settat, Morocco

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Mohamed Ahakoud Medical Genetics Laboratory, University Hospital Center Hassan II, Fez, Morocco

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Amina Ameli Department of Pediatric Endocrinology, University Hospital Center Hassan II, Fez, Morocco

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Laila Bouguenouch Medical Genetics Laboratory, University Hospital Center Hassan II, Fez, Morocco

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Hicham Bekkari Laboratory of Biotechnology, Environment, Food, and Health, Faculty of Sciences Dhar El Mahraz, Sidi Mohammed Ben Abdellah University, Fez, Morocco

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pediatric endocrinology department or during karyotype analysis at the medical genetics laboratory. All parents or legal guardians agreed to take part in this study. Detailed clinical data were obtained from the patient’s medical records, including age

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