{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:39:05Z","timestamp":1791326345966,"version":"4.3.1"},"reference-count":78,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T00:00:00Z","timestamp":1632441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Prader-Willi syndrome (PWS) is a complex genetic syndrome characterized by hyperphagia, intellectual disability, hypotonia and hypothalamic dysfunction. Adults with PWS often have hormone deficiencies, hypogonadism being the most common. Untreated male hypogonadism can aggravate PWS-related health issues including muscle weakness, obesity, osteoporosis, and fatigue. Therefore, timely diagnosis and treatment of male hypogonadism is important. In this article, we share our experience with hypogonadism and its treatment in adult males with PWS and present a review of the literature. In order to report the prevalence and type of hypogonadism, treatment regimen and behavioral issues, we retrospectively collected data on medical interviews, physical examinations, biochemical measurements and testosterone replacement therapy (TRT) in 57 Dutch men with PWS. Fifty-six (98%) of the patients had either primary, central or combined hypogonadism. Untreated hypogonadism was associated with higher body mass index and lower hemoglobin concentrations. TRT was complicated by behavioral challenges in one third of the patients. Undertreatment was common and normal serum testosterone levels were achieved in only 30% of the patients. Based on the Dutch cohort data, review of the literature and an international expert panel discussion, we provide a practical algorithm for TRT in adult males with PWS in order to prevent undertreatment and related adverse health outcomes.<\/jats:p>","DOI":"10.3390\/jcm10194361","type":"journal-article","created":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T20:15:32Z","timestamp":1632514532000},"page":"4361","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Hypogonadism in Adult Males with Prader-Willi Syndrome\u2014Clinical Recommendations Based on a Dutch Cohort Study, Review of the Literature and an International Expert Panel Discussion"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0738-0275","authenticated-orcid":false,"given":"Karlijn","family":"Pellikaan","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"},{"name":"Center for Adults with Rare Genetic Syndromes, Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"},{"name":"Dutch Center of Reference for Prader-Willi Syndrome, 3015 GD Rotterdam, The Netherlands"},{"name":"Academic Center for Growth Disorders, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yassine","family":"Ben Brahim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"},{"name":"Center for Adults with Rare Genetic Syndromes, Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"},{"name":"Dutch Center of Reference for Prader-Willi Syndrome, 3015 GD Rotterdam, The Netherlands"},{"name":"Academic Center for Growth Disorders, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8333-1512","authenticated-orcid":false,"given":"Anna G. W.","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"},{"name":"Center for Adults with Rare Genetic Syndromes, Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"},{"name":"Dutch Center of Reference for Prader-Willi Syndrome, 3015 GD Rotterdam, The Netherlands"},{"name":"Academic Center for Growth Disorders, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Davidse","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"},{"name":"Center for Adults with Rare Genetic Syndromes, Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"},{"name":"Dutch Center of Reference for Prader-Willi Syndrome, 3015 GD Rotterdam, The Netherlands"},{"name":"Academic Center for Growth Disorders, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Poitou","sequence":"additional","affiliation":[{"name":"Assistance Publique-H\u00f4pitaux de Paris, Rare Diseases Center of Reference \u2018Prader-Willi Syndrome and Obesity with Eating Disorders\u2019 (PRADORT), Nutrition Department, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, F-75013 Paris, France"},{"name":"International Network for Research, Management & Education on Adults with PWS (INfoRMEd-PWS)"},{"name":"ENDO-ERN (European Reference Network)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8988-6260","authenticated-orcid":false,"given":"Muriel","family":"Coupaye","sequence":"additional","affiliation":[{"name":"Assistance Publique-H\u00f4pitaux de Paris, Rare Diseases Center of Reference \u2018Prader-Willi Syndrome and Obesity with Eating Disorders\u2019 (PRADORT), Nutrition Department, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, F-75013 Paris, France"},{"name":"International Network for Research, Management & Education on Adults with PWS (INfoRMEd-PWS)"},{"name":"ENDO-ERN (European Reference Network)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8179-7071","authenticated-orcid":false,"given":"Anthony P.","family":"Goldstone","sequence":"additional","affiliation":[{"name":"International Network for Research, Management & Education on Adults with PWS (INfoRMEd-PWS)"},{"name":"PsychoNeuroEndocrinology Research Group, Centre for Neuropsychopharmacology, Division of Psychiatry, and Computational, Cognitive and Clinical Neuroimaging Laboratory, Department of Brain Sciences, Faculty of Medicine, Hammersmith Hospital, London W12 0NN, UK"},{"name":"Department of Endocrinology, Imperial College Healthcare NHS Trust, London W12 0HS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3980-1927","authenticated-orcid":false,"given":"Charlotte","family":"H\u00f8ybye","sequence":"additional","affiliation":[{"name":"International Network for Research, Management & Education on Adults with PWS (INfoRMEd-PWS)"},{"name":"ENDO-ERN (European Reference Network)"},{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden"},{"name":"Department of Endocrinology, Karolinska University Hospital, 171 76 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2521-0357","authenticated-orcid":false,"given":"Tania P.","family":"Markovic","sequence":"additional","affiliation":[{"name":"International Network for Research, Management & Education on Adults with PWS (INfoRMEd-PWS)"},{"name":"Metabolism & Obesity Services, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia"},{"name":"Charles Perkins Centre, Faculty of Medicine and Health, University of Sydney, Sydney, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4708-2544","authenticated-orcid":false,"given":"Graziano","family":"Grugni","sequence":"additional","affiliation":[{"name":"International Network for Research, Management & Education on Adults with PWS (INfoRMEd-PWS)"},{"name":"ENDO-ERN (European Reference Network)"},{"name":"Division of Auxology, Istituto Auxologico Italiano, IRCCS, 28824 Piancavallo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3548-7114","authenticated-orcid":false,"given":"Antonino","family":"Crin\u00f2","sequence":"additional","affiliation":[{"name":"International Network for Research, Management & Education on Adults with PWS (INfoRMEd-PWS)"},{"name":"Reference Center for Prader-Willi Syndrome, Bambino Ges\u00f9 Hospital, Research Institute, 00050 Palidoro (Rome), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8472-9189","authenticated-orcid":false,"given":"Assumpta","family":"Caix\u00e0s","sequence":"additional","affiliation":[{"name":"International Network for Research, Management & Education on Adults with PWS (INfoRMEd-PWS)"},{"name":"Endocrinology and Nutrition Department, Parc Taul\u00ed Hospital Universitari, Institut d\u2019Investigaci\u00f3 I Innovaci\u00f3 Parc Taul\u00ed I3PT, Department of Medicine, Universitat Aut\u00f2noma de Barcelona, 08208 Sabadell, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talia","family":"Eldar-Geva","sequence":"additional","affiliation":[{"name":"The Israel Multidisciplinary Prader-Willi Syndrome Clinic, Jerusalem 9103102, Israel"},{"name":"Reproductive Endocrinology and Genetics Unit, Department of Obstetrics and Gynecology, Shaare-Zedek Medical Center, Jerusalem 9103102, Israel"},{"name":"Hebrew University School of Medicine, Jerusalem 9112102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7499-4023","authenticated-orcid":false,"given":"Harry J.","family":"Hirsch","sequence":"additional","affiliation":[{"name":"The Israel Multidisciplinary Prader-Willi Syndrome Clinic, Jerusalem 9103102, Israel"},{"name":"Department of Pediatrics, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varda","family":"Gross-Tsur","sequence":"additional","affiliation":[{"name":"The Israel Multidisciplinary Prader-Willi Syndrome Clinic, Jerusalem 9103102, Israel"},{"name":"Hebrew University School of Medicine, Jerusalem 9112102, Israel"},{"name":"Neuropediatrics Unit, Department of Pediatrics, Shaare Zedek Medical Center, Jerusalem 9103102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2911-0524","authenticated-orcid":false,"given":"Merlin G.","family":"Butler","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry, Behavioral Sciences and Pediatrics, University of Kansas Medical Center, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sjoerd A. A.","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"},{"name":"Erasmus Medical Center, Department of Clinical Chemistry, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1059-0126","authenticated-orcid":false,"given":"Aart J.","family":"van der Lely","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura C. G.","family":"de Graaff","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"},{"name":"Center for Adults with Rare Genetic Syndromes, Department of Internal Medicine, Division of Endocrinology, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"},{"name":"Dutch Center of Reference for Prader-Willi Syndrome, 3015 GD Rotterdam, The Netherlands"},{"name":"Academic Center for Growth Disorders, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"},{"name":"International Network for Research, Management & Education on Adults with PWS (INfoRMEd-PWS)"},{"name":"ENDO-ERN (European Reference Network)"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"126","DOI":"10.6065\/apem.2016.21.3.126","article-title":"Genetics of Prader-Willi syndrome and Prader-Will-Like syndrome","volume":"21","author":"Cheon","year":"2016","journal-title":"Ann. 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