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Gregory Knowles Walsall Manor Hospital, Walsall, UK

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Emily Warmington College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

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Lisa M Shepherd Department of Endocrinology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK

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Jonathan M Hazlehurst Department of Endocrinology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
Institute of Applied Health Research, University of Birmingham, Birmingham, UK

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Anne de Bray Department of Endocrinology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK

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Helena Gleeson Department of Endocrinology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK

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Wiebke Arlt Department of Endocrinology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Medical Research Council London Institute of Medical Sciences, London, UK

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Alessandro Prete Department of Endocrinology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
NIHR Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK

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Introduction Primary adrenal insufficiency (PAI) is characterised by inadequate steroid hormone secretion caused by intrinsic adrenal cortex disease ( 1 ). The most common causes of PAI are Addison’s disease (AD), usually resulting from

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Simone Martins de Castro Hospital Materno Infantil Presidente Vargas, Newborn Screening Referral Center, Porto Alegre, RS, Brazil
Department of Analysis, Universidade Federal do Rio Grande do Sul (UFRGS), School of Pharmacy, Porto Alegre, RS, Brazil

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Paloma Wiest Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil

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Poli Mara Spritzer Division of Endocrinology, Department of Physiology, Universidade Federal do Rio Grande do Sul (UFRGS), Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil

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Cristiane Kopacek Hospital Materno Infantil Presidente Vargas, Newborn Screening Referral Center, Porto Alegre, RS, Brazil
Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
Department of Pediatrics, Universidade Federal do Rio Grande do Sul (UFRGS), Medical School, Porto Alegre, RS, Brazil

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overlapping disease spectrum because many compound heterozygous patients carry more than one mutation on either or both CYP21A2 alleles ( 7 ). In salt-wasting CAH, there is no cortisol or aldosterone production with a consequent increase in steroid

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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 and Menopause, Cuiabá, Mato Grosso, Brazil

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Cinthia Marenza Ormond Tropical Institute of Reproductive Medicine and Menopause, Cuiabá, Mato Grosso, Brazil

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

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Nayara de Souza Santos Department of Gynecology and Obstetrics, Medical School, Federal University of Mato Grosso, Cuiabá, Mato Grosso, Brazil
Tropical Institute of Reproductive Medicine and Menopause, Cuiabá, Mato Grosso, Brazil

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Camila Regis Banhara Department of Gynecology and Obstetrics, Medical School, Federal University of Mato Grosso, Cuiabá, Mato Grosso, Brazil
Tropical Institute of Reproductive Medicine and Menopause, Cuiabá, Mato Grosso, Brazil

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

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sulfotransferase (SULT2 A1) drive these precursors toward the synthesis of ∆4 steroids and dehydroepiandrosterone sulfate (DHEAS), respectively ( 7 ). After exclusion of other hyperandrogenemic conditions such as hyperprolactinemia, thyroid dysfunction and the

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Florian Schederecker Institute of Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH), Neuherberg, Germany

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Alexander Cecil Molecular Endocrinology and Metabolism, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

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Cornelia Prehn Molecular Endocrinology and Metabolism, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

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Jana Nano Institute of Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH), Neuherberg, Germany

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Wolfgang Koenig Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany
Deutsches Herzzentrum München, Technische Universität München, DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany

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Jerzy Adamski Molecular Endocrinology and Metabolism, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

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Tanja Zeller Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany
German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Germany

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Annette Peters Institute of Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH), Neuherberg, Germany
German Centre for Cardiovascular Research (DZHK), Partner Site Munich, Munich, Germany

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Barbara Thorand Institute of Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH), Neuherberg, Germany

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, missing values in at least one of the cofounding covariates, persons treated with exogenous sexual hormones (anti-estrogens, androgens, anti-androgens, enzyme-inhibitors, gonadotropin-releasing hormone analogs and anabolic steroids). Further, we excluded

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Rajae Talbi Department of Medicine, Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA

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Victor M Navarro Department of Medicine, Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA

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steroids leading to complementary roles in maintaining reproductive success. Kiss1 AVPV/PeN neurons, which are vestigial in males, have been shown to play a major role in driving the preovulatory LH surge in females in response to the positive feedback of

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Frans H H Leenen Brain and Heart Research Group, University of Ottawa Heart Institute, Ottawa, Ontario, Canada

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Mordecai P Blaustein Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA
Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA

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John M Hamlyn Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA

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1991, a substance ‘indistinguishable from ouabain’ was identified by mass spectroscopy (MS) as an endogenous cardiotonic steroid (CTS) in human plasma ( 54 ). This discovery was validated by MS and NMR identification of EO in bovine, rodent and human

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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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used a fixed average level of albumin in both the algorithm by Vermeulen et al. and Zakharov et al. Both testosterone and SHBG were measured using immunoassays. Measurements of sex steroids by use of immunoassays have been criticized for being less

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Mélanie Rouleau Division of Urology, Department of Surgery and Cancer Research Center, Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Québec, Québec, Canada

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Francis Lemire Division of Urology, Department of Surgery and Cancer Research Center, Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Québec, Québec, Canada

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Michel Déry Biochemistry Service, Medical Laboratory Department, CHU de Québec-Université Laval, Québec, Québec, Canada

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Benoît Thériault Division of Urology, Department of Surgery and Cancer Research Center, Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Québec, Québec, Canada

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Gabriel Dubois Division of Urology, Department of Surgery and Cancer Research Center, Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Québec, Québec, Canada

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Yves Fradet Division of Urology, Department of Surgery and Cancer Research Center, Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Québec, Québec, Canada

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Paul Toren Division of Urology, Department of Surgery and Cancer Research Center, Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Québec, Québec, Canada

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Chantal Guillemette Pharmacy Faculty, Université Laval and CHU de Québec-Université Laval, Québec, Québec, Canada

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Louis Lacombe Division of Urology, Department of Surgery and Cancer Research Center, Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Québec, Québec, Canada

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Laurence Klotz Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada

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Fred Saad Centre Hospitalier de l’Université de Montréal, Montréal, Québec, Canada

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Dominique Guérette Biochemistry Service, Medical Laboratory Department, CHU de Québec-Université Laval, Québec, Québec, Canada

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Frédéric Pouliot Division of Urology, Department of Surgery and Cancer Research Center, Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Québec, Québec, Canada

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(IA) methods. Although liquid chromatography–tandem MS (LC–MS/MS) is recognized as the gold standard method to measure steroid levels ( 18 ), MS requires specialized equipment and highly skilled technicians, which prevents its use in most clinical

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Jonneke J Hollanders Department of Pediatric Endocrinology, VU University Medical Center, Amsterdam, The Netherlands

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Bibian van der Voorn Department of Pediatric Endocrinology, VU University Medical Center, Amsterdam, The Netherlands

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Noera Kieviet Department of Pediatrics, Psychiatry Obstetrics Pediatrics Expert Center, OLVG West, Amsterdam, The Netherlands

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Koert M Dolman Department of Pediatrics, Psychiatry Obstetrics Pediatrics Expert Center, OLVG West, Amsterdam, The Netherlands

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Yolanda B de Rijke Department of Clinical Chemistry, Erasmus MC, University Medical Center, Rotterdam, The Netherlands

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Erica L T van den Akker Department of Pediatric Endocrinology, Erasmus MC Sophia Children’s Hospital, Rotterdam, The Netherlands

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Joost Rotteveel Department of Pediatric Endocrinology, VU University Medical Center, Amsterdam, The Netherlands

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Adriaan Honig Department of Pediatrics, Psychiatry Obstetrics Pediatrics Expert Center, OLVG West, Amsterdam, The Netherlands
Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands

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Martijn J J Finken Department of Pediatric Endocrinology, VU University Medical Center, Amsterdam, The Netherlands

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throughout pregnancy ( 4 ). During early gestation, maternal GCs are the main supply. By the second half of gestation, the fetal adrenal starts producing its own steroids, predominantly sex steroids (which serve as a substrate for the placental production of

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Gabriella Oliveira Lima Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Alex Luiz Menezes da Silva Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Julianne Elba Cunha Azevedo Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Chirlene Pinheiro Nascimento Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Luana Rodrigues Vieira Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Akira Otake Hamoy Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Luan Oliveira Ferreira Laboratory of Experimental Neuropathology, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Verônica Regina Lobato Oliveira Bahia Multidisciplinary Laboratory of Animal Morphology, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Nilton Akio Muto Amazon Bioactive Compounds Valorization Center, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Dielly Catrina Favacho Lopes Laboratory of Experimental Neuropathology, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Moisés Hamoy Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Karonova T Vitamin D supplementation guidelines . Journal of Steroid Biochemistry and Molecular Biology 2018 175 125 – 135 . ( https://doi.org/10.1016/j.jsbmb.2017.01.021 ) 5 Vieth R Why the optimal requirement for vitamin D3 is probably much higher

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