8a5a691ceb176f56021b053882b6c0c3 pmc_34640379.pdf 7904376fd59f902c9da176431ada058696bf5ef5 pmc_34640379.pdf e5428d433caf3ec3e7a2b31591ba5d1a347319ef46a7473e51ee37d2db478342 pmc_34640379.pdf Title: Hypogonadism in Adult Males 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 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. Keywords: Prader-Willi syndrome; hypogonadism; pituitary gland; testosterone; 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, Sjoerd A. A. van den Berg, Aart J. van der Lely and Laura C. G. de Graaff Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Sep 28 10:00:10 2021 CEST ModDate: Tue Sep 28 10:05:50 2021 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 28 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2853317 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- XLVVVP+VnURWPalladioL Type 1 Custom yes yes no 10 0 BAVXUF+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 BWAVYU+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 RHPWOK+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 KGSVEK+VnURWPalladioL-Bold 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 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 65 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 69 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes no 93 0 HJMBPF+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 106 0 HJMBPH+PalatinoLinotype TrueType WinAnsi yes yes no 109 0 HJMBPJ+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 112 0 HMCGLA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 126 0 HMCGLC+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 129 0 HMCGME+PalatinoLinotype TrueType WinAnsi yes yes no 132 0 HMCHAD+SimSun CID TrueType Identity-H yes yes yes 135 0 GQWIGS+CMSY10 Type 1 Builtin yes yes no 152 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-02 03:38:58 CEST RepresentationInformation: pmc_34640379.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 12:05:52 CEST Size: 2853317 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 578 FreeObjects: 9 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: Literature Search Destination: subsection.2.1 Item: Title: Expert Opinion Destination: subsection.2.2 Item: Title: Data Analysis Destination: subsection.2.3 Item: Title: Results Destination: section.3 Children: Item: Title: Baseline Characteristics Destination: subsection.3.1 Item: Title: Hypogonadism Destination: subsection.3.2 Item: Title: Effect of Untreated Hypogonadism Destination: subsection.3.3 Item: Title: Types of Hypogonadism Destination: subsection.3.4 Item: Title: Literature Review Destination: subsection.3.5 Item: Title: Expert Panel and Clinical Recommendations Destination: subsection.3.6 Item: Title: Discussion Destination: section.4 Children: Item: Title: Type of Hypogonadism Destination: subsection.4.1 Item: Title: Undertreatment Destination: subsection.4.2 Item: Title: Importance of Treatment of Hypogonadism Destination: subsection.4.3 Children: Item: Title: Osteoporosis Destination: subsubsection.4.3.1 Item: Title: Muscle and Fat Destination: subsubsection.4.3.2 Item: Title: Fatigue Destination: subsubsection.4.3.3 Item: Title: Cardiovascular Health Destination: subsubsection.4.3.4 Item: Title: TRT Warnings and Precautions Destination: subsection.4.4 Item: Title: Recommendations Destination: subsection.4.5 Children: Item: Title: Interpretation of Hormone Levels Destination: subsubsection.4.5.1 Item: Title: Sleep Apnea Destination: subsubsection.4.5.2 Item: Title: Drug Interactions Destination: subsubsection.4.5.3 Item: Title: Cardiac Failure Destination: subsubsection.4.5.4 Item: Title: Challenging Behavior Destination: subsubsection.4.5.5 Item: Title: Mode of Administration Destination: subsubsection.4.5.6 Item: Title: Erythrocytosis Destination: subsubsection.4.5.7 Item: Title: Prostate and Liver Destination: subsubsection.4.5.8 Item: Title: Non-Compliance Destination: subsubsection.4.5.9 Item: Title: Role of PWS Reference Centers Destination: subsection.4.6 Item: Title: Strengths and Limitations Destination: subsection.4.7 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: Hypogonadism in Adult Males 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, Sjoerd A. A. van den Berg, Aart J. van der Lely and Laura C. G. de Graaff Subject: 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. Keywords: Prader-Willi syndrome; hypogonadism; pituitary gland; testosterone; obesity; puberty Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Sep 28 10:00:10 CEST 2021 ModDate: Tue Sep 28 10:05:50 CEST 2021 ID: 0x65cd39ad27a5dc4d389ff572de65078c, 0x65cd39ad27a5dc4d389ff572de65078c Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: BWAVYU+URWPalladioL-Bold FontSubset: true FirstChar: 2 LastChar: 248 FontDescriptor: FontName: BWAVYU+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: RHPWOK+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: RHPWOK+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: GQWIGS+CMSY10 FontSubset: true FirstChar: 0 LastChar: 21 FontDescriptor: FontName: GQWIGS+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 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