{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:41:40Z","timestamp":1788460900152,"version":"build-2803163510"},"reference-count":111,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T00:00:00Z","timestamp":1639094400000},"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 rare neuroendocrine genetic syndrome. Characteristics of PWS include hyperphagia, hypotonia, and intellectual disability. Pituitary hormone deficiencies, caused by hypothalamic dysfunction, are common and hypogonadism is the most prevalent. Untreated hypogonadism can cause osteoporosis, which is already an important issue in PWS. Therefore, timely detection and treatment of hypogonadism is crucial. To increase understanding and prevent undertreatment, we (1) performed a cohort study in the Dutch PWS population, (2) thoroughly reviewed the literature on female hypogonadism in PWS and (3) provide clinical recommendations on behalf of an international expert panel. For the cohort study, we retrospectively collected results of a systematic health screening in 64 female adults with PWS, which included a medical questionnaire, medical file search, medical interview, physical examination and biochemical measurements. Our data show that hypogonadism is frequent in females with PWS (94%), but is often undiagnosed and untreated. This could be related to unfamiliarity with the syndrome, fear of behavioral changes, hygienic concerns, or drug interactions. To prevent underdiagnosis and undertreatment, we provide practical recommendations for the screening and treatment of hypogonadism in females with PWS.<\/jats:p>","DOI":"10.3390\/jcm10245781","type":"journal-article","created":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T08:17:58Z","timestamp":1639124278000},"page":"5781","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Hypogonadism in Women 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 Centre 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 Centre 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 Centre 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 Centre 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":"Rare Diseases Center of Reference \u2018Prader-Willi Syndrome and Obesity with Eating Disorders\u2019 (PRADORT), Nutrition Department, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Assistance Publique-H\u00f4pitaux de Paris, 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":"Rare Diseases Center of Reference \u2018Prader-Willi Syndrome and Obesity with Eating Disorders\u2019 (PRADORT), Nutrition Department, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Assistance Publique-H\u00f4pitaux de Paris, 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, Imperial College London, Hammersmith Hospital, London W12 0NN, UK"},{"name":"Department of Endocrinology, Imperial College Healthcare NHS Trust, Hammersmith Hospital, 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, 17176 Stockholm, Sweden"},{"name":"Center for Adults with Rare Genetic Syndromes, Department of Internal Medicine, Division of Department of Endocrinology, Karolinska University Hospital, 17176 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":"Divison 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, 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, Institut d\u2019Investigaci\u00f3 I Innovaci\u00f3 Parc Taul\u00ed I3PT, Parc Taul\u00ed Hospital Universitari, 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"}]},{"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7128-8801","authenticated-orcid":false,"given":"Paul-Hugo M.","family":"van der Kuy","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"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":"Department of Clinical Chemistry, Erasmus University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7182-3571","authenticated-orcid":false,"given":"Jenny A.","family":"Visser","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"}]},{"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. 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