Application of the Athlete Biological Passport Approach to the Detection of Growth Hormone Doping
Because of its anabolic and lipolytic properties, growth hormone (GH) use is prohibited in sport. Two methods based on population-derived decision limits are currently used to detect human GH (hGH) abuse: the hGH Biomarkers Test and the Isoforms Differential Immunoassay. We tested the hypothesis tha...
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| Veröffentlicht in: | The journal of clinical endocrinology and metabolism 2022-02, Vol.107 (3), p.649-659 |
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| container_title | The journal of clinical endocrinology and metabolism |
| container_volume | 107 |
| creator | Equey, Tristan Pastor, Antoni de la Torre Fornell, Rafael Thomas, Andreas Giraud, Sylvain Thevis, Mario Kuuranne, Tiia Baume, Norbert Barroso, Osquel Aikin, Reid |
| description | Because of its anabolic and lipolytic properties, growth hormone (GH) use is prohibited in sport. Two methods based on population-derived decision limits are currently used to detect human GH (hGH) abuse: the hGH Biomarkers Test and the Isoforms Differential Immunoassay.
We tested the hypothesis that longitudinal profiling of hGH biomarkers through application of the Athlete Biological Passport (ABP) has the potential to flag hGH abuse.
Insulin-like growth factor 1 (IGF-1) and procollagen III peptide (P-III-NP) distributions were obtained from 7 years of anti-doping data in elite athletes (n = 11 455) and applied as priors to analyze individual profiles from an hGH administration study in recreational athletes (n = 35). An open-label, randomized, single-site, placebo-controlled administration study was carried out with individuals randomly assigned to 4 arms: placebo, or 3 different doses of recombinant hGH. Serum samples were analyzed for IGF-1, P-III-NP, and hGH isoforms and the performance of a longitudinal, ABP-based approach was evaluated.
An ABP-based approach set at a 99% specificity level flagged 20/27 individuals receiving hGH treatment, including 17/27 individuals after cessation of the treatment. ABP sensitivity ranged from 12.5% to 71.4% across the hGH concentrations tested following 7 days of treatment, peaking at 57.1% to 100% after 21 days of treatment, and was maintained between 37.5% and 71.4% for the low and high dose groups 1 week after cessation of treatment.
These findings demonstrate that longitudinal profiling of hGH biomarkers can provide suitable performance characteristics for use in anti-doping programs. |
| doi_str_mv | 10.1210/clinem/dgab799 |
| format | Article |
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We tested the hypothesis that longitudinal profiling of hGH biomarkers through application of the Athlete Biological Passport (ABP) has the potential to flag hGH abuse.
Insulin-like growth factor 1 (IGF-1) and procollagen III peptide (P-III-NP) distributions were obtained from 7 years of anti-doping data in elite athletes (n = 11 455) and applied as priors to analyze individual profiles from an hGH administration study in recreational athletes (n = 35). An open-label, randomized, single-site, placebo-controlled administration study was carried out with individuals randomly assigned to 4 arms: placebo, or 3 different doses of recombinant hGH. Serum samples were analyzed for IGF-1, P-III-NP, and hGH isoforms and the performance of a longitudinal, ABP-based approach was evaluated.
An ABP-based approach set at a 99% specificity level flagged 20/27 individuals receiving hGH treatment, including 17/27 individuals after cessation of the treatment. ABP sensitivity ranged from 12.5% to 71.4% across the hGH concentrations tested following 7 days of treatment, peaking at 57.1% to 100% after 21 days of treatment, and was maintained between 37.5% and 71.4% for the low and high dose groups 1 week after cessation of treatment.
These findings demonstrate that longitudinal profiling of hGH biomarkers can provide suitable performance characteristics for use in anti-doping programs.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/clinem/dgab799</identifier><identifier>PMID: 34726230</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Adult ; Athletes ; Athletes - statistics & numerical data ; Biomarkers - blood ; Doping in Sports - prevention & control ; Female ; Healthy Volunteers ; Human Growth Hormone - administration & dosage ; Human Growth Hormone - blood ; Humans ; Insulin-Like Growth Factor I - analysis ; Male ; Passports ; Peptide Fragments - blood ; Performance-Enhancing Substances - administration & dosage ; Performance-Enhancing Substances - blood ; Procollagen - blood ; Somatotropin ; Substance Abuse Detection - methods</subject><ispartof>The journal of clinical endocrinology and metabolism, 2022-02, Vol.107 (3), p.649-659</ispartof><rights>The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><rights>COPYRIGHT 2022 Oxford University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c402t-7546e880e3cf3fd5403a03bced5e670f34d66b979e8562dae922032339fe33813</citedby><cites>FETCH-LOGICAL-c402t-7546e880e3cf3fd5403a03bced5e670f34d66b979e8562dae922032339fe33813</cites><orcidid>0000-0001-7495-0488</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34726230$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Equey, Tristan</creatorcontrib><creatorcontrib>Pastor, Antoni</creatorcontrib><creatorcontrib>de la Torre Fornell, Rafael</creatorcontrib><creatorcontrib>Thomas, Andreas</creatorcontrib><creatorcontrib>Giraud, Sylvain</creatorcontrib><creatorcontrib>Thevis, Mario</creatorcontrib><creatorcontrib>Kuuranne, Tiia</creatorcontrib><creatorcontrib>Baume, Norbert</creatorcontrib><creatorcontrib>Barroso, Osquel</creatorcontrib><creatorcontrib>Aikin, Reid</creatorcontrib><title>Application of the Athlete Biological Passport Approach to the Detection of Growth Hormone Doping</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Because of its anabolic and lipolytic properties, growth hormone (GH) use is prohibited in sport. Two methods based on population-derived decision limits are currently used to detect human GH (hGH) abuse: the hGH Biomarkers Test and the Isoforms Differential Immunoassay.
We tested the hypothesis that longitudinal profiling of hGH biomarkers through application of the Athlete Biological Passport (ABP) has the potential to flag hGH abuse.
Insulin-like growth factor 1 (IGF-1) and procollagen III peptide (P-III-NP) distributions were obtained from 7 years of anti-doping data in elite athletes (n = 11 455) and applied as priors to analyze individual profiles from an hGH administration study in recreational athletes (n = 35). An open-label, randomized, single-site, placebo-controlled administration study was carried out with individuals randomly assigned to 4 arms: placebo, or 3 different doses of recombinant hGH. Serum samples were analyzed for IGF-1, P-III-NP, and hGH isoforms and the performance of a longitudinal, ABP-based approach was evaluated.
An ABP-based approach set at a 99% specificity level flagged 20/27 individuals receiving hGH treatment, including 17/27 individuals after cessation of the treatment. ABP sensitivity ranged from 12.5% to 71.4% across the hGH concentrations tested following 7 days of treatment, peaking at 57.1% to 100% after 21 days of treatment, and was maintained between 37.5% and 71.4% for the low and high dose groups 1 week after cessation of treatment.
These findings demonstrate that longitudinal profiling of hGH biomarkers can provide suitable performance characteristics for use in anti-doping programs.</description><subject>Adult</subject><subject>Athletes</subject><subject>Athletes - statistics & numerical data</subject><subject>Biomarkers - blood</subject><subject>Doping in Sports - prevention & control</subject><subject>Female</subject><subject>Healthy Volunteers</subject><subject>Human Growth Hormone - administration & dosage</subject><subject>Human Growth Hormone - blood</subject><subject>Humans</subject><subject>Insulin-Like Growth Factor I - analysis</subject><subject>Male</subject><subject>Passports</subject><subject>Peptide Fragments - blood</subject><subject>Performance-Enhancing Substances - administration & dosage</subject><subject>Performance-Enhancing Substances - blood</subject><subject>Procollagen - blood</subject><subject>Somatotropin</subject><subject>Substance Abuse Detection - methods</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkctLxDAQxoMouj6uHqXgxUs1j7Zpjuv6BEEPCt5CNp3sRtKmJlnE_97orp5kDgMzv2_4hg-hY4LPCSX4Qjs7QH_RLdScC7GFJkRUdcmJ4NtogjElpeD0dQ_tx_iGMamqmu2iPVZx2lCGJ0hNx9FZrZL1Q-FNkZZQTNPSQYLi0nrnF3npiicV4-hDKjIevNLLIvkf9iqD-ld8G_xHWhZ3PvR-yDs_2mFxiHaMchGONv0AvdxcP8_uyofH2_vZ9KHUFaap5HXVQNtiYNow09UVZgqzuYauhoZjw6quaeaCC2jrhnYKBKWYUcaEAcZawg7Q2fpuNvi-gphkb6MG59QAfhUlrUX-WLS0zujpGl0oB9IOxqeg9Dcup5w3-TKhTabO_6FyddBbnR80Ns__E-jgYwxg5Bhsr8KnJFh-pyXXaclNWllwsrG8mvfQ_eG_8bAvv4uQ9w</recordid><startdate>20220217</startdate><enddate>20220217</enddate><creator>Equey, Tristan</creator><creator>Pastor, Antoni</creator><creator>de la Torre Fornell, Rafael</creator><creator>Thomas, Andreas</creator><creator>Giraud, Sylvain</creator><creator>Thevis, Mario</creator><creator>Kuuranne, Tiia</creator><creator>Baume, Norbert</creator><creator>Barroso, Osquel</creator><creator>Aikin, Reid</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7495-0488</orcidid></search><sort><creationdate>20220217</creationdate><title>Application of the Athlete Biological Passport Approach to the Detection of Growth Hormone Doping</title><author>Equey, Tristan ; Pastor, Antoni ; de la Torre Fornell, Rafael ; Thomas, Andreas ; Giraud, Sylvain ; Thevis, Mario ; Kuuranne, Tiia ; Baume, Norbert ; Barroso, Osquel ; Aikin, Reid</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c402t-7546e880e3cf3fd5403a03bced5e670f34d66b979e8562dae922032339fe33813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adult</topic><topic>Athletes</topic><topic>Athletes - statistics & numerical data</topic><topic>Biomarkers - blood</topic><topic>Doping in Sports - prevention & control</topic><topic>Female</topic><topic>Healthy Volunteers</topic><topic>Human Growth Hormone - administration & dosage</topic><topic>Human Growth Hormone - blood</topic><topic>Humans</topic><topic>Insulin-Like Growth Factor I - analysis</topic><topic>Male</topic><topic>Passports</topic><topic>Peptide Fragments - blood</topic><topic>Performance-Enhancing Substances - administration & dosage</topic><topic>Performance-Enhancing Substances - blood</topic><topic>Procollagen - blood</topic><topic>Somatotropin</topic><topic>Substance Abuse Detection - methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Equey, Tristan</creatorcontrib><creatorcontrib>Pastor, Antoni</creatorcontrib><creatorcontrib>de la Torre Fornell, Rafael</creatorcontrib><creatorcontrib>Thomas, Andreas</creatorcontrib><creatorcontrib>Giraud, Sylvain</creatorcontrib><creatorcontrib>Thevis, Mario</creatorcontrib><creatorcontrib>Kuuranne, Tiia</creatorcontrib><creatorcontrib>Baume, Norbert</creatorcontrib><creatorcontrib>Barroso, Osquel</creatorcontrib><creatorcontrib>Aikin, Reid</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Equey, Tristan</au><au>Pastor, Antoni</au><au>de la Torre Fornell, Rafael</au><au>Thomas, Andreas</au><au>Giraud, Sylvain</au><au>Thevis, Mario</au><au>Kuuranne, Tiia</au><au>Baume, Norbert</au><au>Barroso, Osquel</au><au>Aikin, Reid</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Application of the Athlete Biological Passport Approach to the Detection of Growth Hormone Doping</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2022-02-17</date><risdate>2022</risdate><volume>107</volume><issue>3</issue><spage>649</spage><epage>659</epage><pages>649-659</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><abstract>Because of its anabolic and lipolytic properties, growth hormone (GH) use is prohibited in sport. Two methods based on population-derived decision limits are currently used to detect human GH (hGH) abuse: the hGH Biomarkers Test and the Isoforms Differential Immunoassay.
We tested the hypothesis that longitudinal profiling of hGH biomarkers through application of the Athlete Biological Passport (ABP) has the potential to flag hGH abuse.
Insulin-like growth factor 1 (IGF-1) and procollagen III peptide (P-III-NP) distributions were obtained from 7 years of anti-doping data in elite athletes (n = 11 455) and applied as priors to analyze individual profiles from an hGH administration study in recreational athletes (n = 35). An open-label, randomized, single-site, placebo-controlled administration study was carried out with individuals randomly assigned to 4 arms: placebo, or 3 different doses of recombinant hGH. Serum samples were analyzed for IGF-1, P-III-NP, and hGH isoforms and the performance of a longitudinal, ABP-based approach was evaluated.
An ABP-based approach set at a 99% specificity level flagged 20/27 individuals receiving hGH treatment, including 17/27 individuals after cessation of the treatment. ABP sensitivity ranged from 12.5% to 71.4% across the hGH concentrations tested following 7 days of treatment, peaking at 57.1% to 100% after 21 days of treatment, and was maintained between 37.5% and 71.4% for the low and high dose groups 1 week after cessation of treatment.
These findings demonstrate that longitudinal profiling of hGH biomarkers can provide suitable performance characteristics for use in anti-doping programs.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>34726230</pmid><doi>10.1210/clinem/dgab799</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-7495-0488</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0021-972X |
| ispartof | The journal of clinical endocrinology and metabolism, 2022-02, Vol.107 (3), p.649-659 |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adult Athletes Athletes - statistics & numerical data Biomarkers - blood Doping in Sports - prevention & control Female Healthy Volunteers Human Growth Hormone - administration & dosage Human Growth Hormone - blood Humans Insulin-Like Growth Factor I - analysis Male Passports Peptide Fragments - blood Performance-Enhancing Substances - administration & dosage Performance-Enhancing Substances - blood Procollagen - blood Somatotropin Substance Abuse Detection - methods |
| title | Application of the Athlete Biological Passport Approach to the Detection of Growth Hormone Doping |
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