a84e20be082f4bdcf688e69b0326fe26 pmc_34945077.pdf 3de618c3ca954191994ff90c9350a2322c2b1580 pmc_34945077.pdf dbc636fcb5fe3d25a7a4cff68816d210d94b4a0b2fe90dd353e4452e52faf5c4 pmc_34945077.pdf Title: Hypogonadism in Women with Prader-Willi Syndrome—Clinical Recommendations Based on a Dutch Cohort Study, Review of the Literature and an International Expert Panel Discussion Subject: 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. Keywords: Prader-Willi syndrome; hypogonadism; hypothalamus; pituitary gland; estrogens; menstrual cycle; obesity; puberty Author: Karlijn Pellikaan, Yassine Ben Brahim, Anna G. W. Rosenberg, Kirsten Davidse, Christine Poitou, Muriel Coupaye, Anthony P. Goldstone, Charlotte Høybye, Tania P. Markovic, Graziano Grugni, Antonino Crinò, Assumpta Caixàs, Talia Eldar-Geva, Harry J. Hirsch, Varda Gross-Tsur, Merlin G. Butler, Jennifer L. Miller, Paul-Hugo M. van der Kuy, Sjoerd A. A. van den Berg, Jenny A. Visser, Aart J. van der Lely and Laura C. G. de Graaff Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Dec 10 09:08:31 2021 CET ModDate: Fri Dec 10 09:13:44 2021 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 22 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1774727 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- KGSVEK+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 FTAXPX+VnURWPalladioL Type 1 Custom yes yes no 15 0 BLSBMH+URWPalladioL-Ital Type 1 Custom yes yes no 19 0 KKNOSK+URWPalladioL-Bold Type 1 Custom yes yes no 24 0 KVFIUR+URWPalladioL-Roma Type 1 Custom yes yes no 28 0 XPUSBJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 36 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 39 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 61 0 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ABCDEE+Palatino Linotype TrueType WinAnsi yes yes no 183 0 ABCDEE+Palatino Linotype,Italic TrueType WinAnsi yes yes no 187 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-02 03:37:39 CEST RepresentationInformation: pmc_34945077.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 12:06:35 CEST Size: 1774727 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 640 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Terminology Destination: subsection.2.1 Item: Title: Definition of Hypogonadism Destination: subsection.2.2 Item: Title: Laboratory Measurements Destination: subsection.2.3 Item: Title: Expert Panel Discussion on Diagnosis and Treatment of Hypogonadism Destination: subsection.2.4 Item: Title: Literature Search Destination: subsection.2.5 Item: Title: Data Analysis Destination: subsection.2.6 Item: Title: Results Destination: section.3 Children: Item: Title: Baseline Characteristics Destination: subsection.3.1 Item: Title: Hypogonadism Destination: subsection.3.2 Item: Title: Types of Hypogonadism Destination: subsection.3.3 Item: Title: Hormone Treatment Destination: subsection.3.4 Item: Title: Expert Panel Discussion on Diagnosis and Treatment of Hypogonadism Destination: subsection.3.5 Children: Item: Title: Start Treatment for Hypogonadism Destination: subsubsection.3.5.1 Item: Title: Stop Treatment for Hypogonadism Destination: subsubsection.3.5.2 Item: Title: Literature Review Destination: subsection.3.6 Item: Title: Discussion Destination: section.4 Children: Item: Title: Type of Hypogonadism Destination: subsection.4.1 Item: Title: Ovarian Histology Destination: subsection.4.2 Item: Title: Factors Influencing Hypogonadism in PWS Destination: subsection.4.3 Item: Title: Importance of Treatment of Hypogonadism Destination: subsection.4.4 Children: Item: Title: Bone Health Destination: subsubsection.4.4.1 Item: Title: Muscle and Fat Destination: subsubsection.4.4.2 Item: Title: Psychological Effects Destination: subsubsection.4.4.3 Item: Title: Cardiovascular Risk Destination: subsubsection.4.4.4 Item: Title: Recommendations Destination: subsection.4.5 Children: Item: Title: Assessment of Gonadal Function Destination: subsubsection.4.5.1 Item: Title: Treatment Regimen Destination: subsubsection.4.5.2 Item: Title: Drug Interactions Destination: subsubsection.4.5.3 Item: Title: Intellectual Disability and Menstrual Hygiene Destination: subsubsection.4.5.4 Item: Title: Challenging Behavior and Psychotic Symptoms Destination: subsubsection.4.5.5 Item: Title: Thrombosis Destination: subsubsection.4.5.6 Item: Title: Weight Gain Destination: subsubsection.4.5.7 Item: Title: Breast Cancer Destination: subsubsection.4.5.8 Item: Title: Sex for Food Destination: subsubsection.4.5.9 Item: Title: Non-Compliance Destination: subsubsection.4.5.10 Item: Title: Discontinuation of HHT Destination: subsubsection.4.5.11 Item: Title: Strengths and Limitations Destination: subsection.4.6 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: Hypogonadism in Women with Prader-Willi Syndrome Clinical Recommendations Based on a Dutch Cohort Study, Review of the Literature and an International Expert Panel Discussion Author: Karlijn Pellikaan, Yassine Ben Brahim, Anna G. W. Rosenberg, Kirsten Davidse, Christine Poitou, Muriel Coupaye, Anthony P. Goldstone, Charlotte Høybye, Tania P. Markovic, Graziano Grugni, Antonino Crinò, Assumpta Caixàs, Talia Eldar-Geva, Harry J. Hirsch, Varda Gross-Tsur, Merlin G. Butler, Jennifer L. Miller, Paul-Hugo M. van der Kuy, Sjoerd A. A. van den Berg, Jenny A. Visser, Aart J. van der Lely and Laura C. G. de Graaff Subject: 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. Keywords: Prader-Willi syndrome; hypogonadism; hypothalamus; pituitary gland; estrogens; menstrual cycle; obesity; puberty Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Dec 10 09:08:31 CET 2021 ModDate: Fri Dec 10 09:13:44 CET 2021 ID: 0x14870aafeac6fe6c8c585ede6946a917, 0x14870aafeac6fe6c8c585ede6946a917 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: BLSBMH+URWPalladioL-Ital FontSubset: true FirstChar: 2 LastChar: 150 FontDescriptor: FontName: BLSBMH+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: JDUPKS+CMSY10 FontSubset: true FirstChar: 0 LastChar: 6 FontDescriptor: FontName: JDUPKS+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: KKNOSK+URWPalladioL-Bold FontSubset: true FirstChar: 2 LastChar: 248 FontDescriptor: FontName: KKNOSK+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true 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