{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T16:24:37Z","timestamp":1787156677376,"version":"build-2736575974"},"update-to":[{"DOI":"10.3310\/nihropenres.14030.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000}}],"reference-count":25,"publisher":"National Institute for Health and Care Research","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"crossref","award":["NIHR301571"],"award-info":[{"award-number":["NIHR301571"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["openresearch.nihr.ac.uk"],"crossmark-restriction":false},"short-container-title":["NIHR Open Res"],"abstract":"<ns5:p>\n                    Background In adults, treatment of GHD with daily GH injection has been shown to improve many clinical features associated with GHD. Currently, many adults with GHD receive GH treatment indefinitely. Short and medium-term studies have demonstrated beneficial effects of GH replacement therapy, including improvements in body composition, metabolic parameters and quality of life. However, uncertainty remains regarding the long-term sustainability of these benefits and the consequences of treatment discontinuation. A randomised controlled trial is needed to understand the impacts of discontinuing long-term GH therapy in adults. Prior to embarking on an RCT, the feasibility of a discontinuation study and the acceptability of randomisation to patients and clinicians need to be assessed. Research aims (a) to explore the current practice of offering discontinuation of long-term GH treatment in adults in the UK and (b) to assess the feasibility of conducting an RCT evaluating GH treatment discontinuation in adults with GHD. Methods This multi-method study comprises of three phases.\n                    <ns5:list list-type=\"bullet\">\n                      <ns5:list-item>\n                        <ns5:p>\u2022 Phase 1: An online survey of endocrine clinicians\u2019 practice of offering discontinuation of long-term GH therapy in adult patients with GHD.<\/ns5:p>\n                      <\/ns5:list-item>\n                      <ns5:list-item>\n                        <ns5:p>\u2022 Phase 2: Feasibility cohort study involving two groups of adult patients with GHD (aged more than 25\u00a0years), who have been on GH treatment for at least 5\u00a0years.: (a) an intervention group consisting of 20\u201325 patients who will be discontinuing their long-term GH treatment for two years and (b) a control group consisting of 20\u201325 patients who will continue with their GH treatment.<\/ns5:p>\n                      <\/ns5:list-item>\n                      <ns5:list-item>\n                        <ns5:p>\u2022 Phase 3: Qualitative study. 10\u201316 participants will be recruited to explore their experiences of participation in the feasibility study using semi-structured interviews.<\/ns5:p>\n                      <\/ns5:list-item>\n                    <\/ns5:list>\n                    Potential benefits This study will provide evidence of current GH treatment discontinuation practice in the UK and determine the feasibility of any future RCT. Long-term, this could promote and underpin the development of the much-needed relevant clinical guidance.\n                  <\/ns5:p>","DOI":"10.3310\/nihropenres.14030.2","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T15:29:08Z","timestamp":1787153348000},"page":"83","update-policy":"https:\/\/doi.org\/10.3310\/nihropenres.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The effects of Growth hormone treatment discontinuation in Adults on Metabolic profile, Body composition and quality Of Life (GAMBOL Study)"],"prefix":"10.3310","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6268-1628","authenticated-orcid":false,"given":"Sherwin","family":"Criseno","sequence":"first","affiliation":[{"name":"Department of Metabolism and Systems Science Birmingham England University of Birmingham College of Medical and Dental Sciences"},{"name":"Centre for Endocrinology, Diabetes and Metabolism Birmingham Birmingham Health Partners"},{"name":"Department of Endocrinology and Metabolism Birmingham England University Hospitals Birmingham NHS Foundation Trust"},{"name":"School of Nursing and Midwifery Birmingham England University of Birmingham Institute of Clinical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0111-2341","authenticated-orcid":false,"given":"Anne","family":"Topping","sequence":"additional","affiliation":[{"name":"School of Nursing and Midwifery Birmingham England University of Birmingham Institute of Clinical Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niki","family":"Karavitaki","sequence":"additional","affiliation":[{"name":"Department of Metabolism and Systems Science Birmingham England University of Birmingham College of Medical and Dental Sciences"},{"name":"Centre for Endocrinology, Diabetes and Metabolism Birmingham Birmingham Health Partners"},{"name":"Department of Endocrinology and Metabolism Birmingham England University Hospitals Birmingham NHS Foundation Trust"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6221","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"R47-R56","DOI":"10.1530\/EJE-18-0306","article-title":"Therapy of endocrine disease: Growth Hormone replacement therapy in adults: 30 years of personal clinical experience.","volume":"179","author":"J J\u00f8rgensen","year":"2018","journal-title":"Eur J Endocrinol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"387-397","DOI":"10.1111\/j.1365-2265.1992.tb02347.x","article-title":"The Growth Hormone Deficiency syndrome in adults.","volume":"37","author":"R Cuneo","year":"1992","journal-title":"Clin Endocrinol (Oxf)."},{"key":"ref3","first-page":"277-287","volume":"21","author":"U Feldt-Rasmussen","year":"2000","journal-title":"Endotext."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"R81-R87","DOI":"10.1530\/EJE-13-0418","article-title":"UK stance on adult GH replacement: the economist vs the endocrinologist.","volume":"169","author":"S Shalet","year":"2013","journal-title":"Eur J Endocrinol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"352-361","DOI":"10.1210\/jc.2012-2940","article-title":"Metabolic profile in Growth Hormone-Deficient (GHD) adults after long-term recombinant human Growth Hormone (GH) therapy.","volume":"98","author":"K Claessen","year":"2013","journal-title":"J Clin Endocrinol Metab."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"294-306","DOI":"10.1007\/s11102-020-01031-5","article-title":"Growth Hormone therapy in adults with Growth Hormone Deficiency: a critical assessment of the literature.","volume":"23","author":"X He","year":"2020","journal-title":"Pituitary."},{"key":"ref7","article-title":"Human Growth Hormone (somatropin) in adults with Growth Hormone Deficiency. NICE technology appraisal guidance [TA64].","year":"2003","journal-title":"NICE."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"263-272","DOI":"10.1530\/EJE-13-0764","article-title":"Abnormal metabolic phenotype in middle-aged GH-Deficient adults despite long-term recombinant human GH replacement.","volume":"170","author":"K Claessen","year":"2013","journal-title":"Eur J Endocrinol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"657-665","DOI":"10.1530\/EJE-10-1170","article-title":"GH replacement therapy in elderly GH-Deficient patients: a systematic review.","volume":"164","author":"N Kokshoorn","year":"2011","journal-title":"Eur J Endocrinol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"701-708","DOI":"10.1530\/eje.1.02283","article-title":"Sustained effects of recombinant GH replacement after 7 years of treatment in adults with GH Deficiency.","volume":"155","author":"A Van der Klaauw","year":"2006","journal-title":"Eur J Endocrinol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"20-39","DOI":"10.1210\/edrv-14\u20131-20","article-title":"Human Growth Hormone and human aging.","volume":"14","author":"E Corpas","year":"1993","journal-title":"Endocr Rev."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"70ra13","DOI":"10.1126\/scitranslmed.3001845","article-title":"Growth Hormone Receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans.","volume":"3","author":"J Guevara-Aguirre","year":"2011","journal-title":"Sci Transl Med."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"2596-2602","DOI":"10.1210\/jcem.84.8.5916","article-title":"The effects of 10 years of recombinant human Growth Hormone (GH) in adult GH-Deficient patients.","volume":"84","author":"J Gibney","year":"1999","journal-title":"J Clin Endocrinol Metab."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"467-475","DOI":"10.1046\/j.1365-2265.2003.01870.x","article-title":"Psychological effects of withdrawal of growth hormone therapy from adults with Growth Hormone Deficiency.","volume":"59","author":"C McMillan","year":"2003","journal-title":"Clin Endocrinol (Oxf)."},{"key":"ref15","article-title":"Osteoporosis: assessing the risk of fragility fracture.","year":"Aug, 2012","journal-title":"NICE CG146."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"e371-e377","DOI":"10.3399\/bjgp12X641492","article-title":"Exploring patients\u2019 reasons for declining contact in a cognitive behavioural therapy randomised controlled trial in primary care.","volume":"62","author":"M Barnes","year":"2012","journal-title":"Br J Gen Pract."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1753-1760","DOI":"10.1177\/1049732315617444","article-title":"Sample size in qualitative interview studies: guided by information power.","volume":"26","author":"K Malterud","year":"2016","journal-title":"Qual Health Res."},{"key":"ref18","first-page":"120-123","article-title":"Teaching thematic analysis: over-coming challenges and developing strategies for effective learning.","volume":"26","author":"V Clarke","year":"2013","journal-title":"Psychologist."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1211-1221","DOI":"10.1016\/j.midw.2013.05.001","article-title":"A systematic review of qualitative evidence on barriers and facilitators to the implementation of task-shifting in midwifery services.","volume":"29","author":"C Colvin","year":"2013","journal-title":"Midwifery."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/1471-2288-13-104","article-title":"An audit of sample sizes for pilot and feasibility trials being undertaken in the United Kingdom registered in the United Kingdom Clinical Research Network database.","volume":"13","author":"S Billingham","year":"2013","journal-title":"BMC Med Res Methodol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"287-291","DOI":"10.1002\/pst.185","article-title":"Sample size of 12 per group rule of thumb for a pilot study.","volume":"4","author":"S Julious","year":"2005","journal-title":"Pharm Stat."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"P1-P9","DOI":"10.1530\/EJE-15-0873","article-title":"GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults.","volume":"174","author":"D Allen","year":"2016","journal-title":"Eur J Endocrinol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"2017","DOI":"10.12688\/f1000research.12057.1","article-title":"Update on GH therapy in adults [version 1; peer review: 3 approved].","volume":"6","author":"C Boguszewski","year":"2017","journal-title":"F1000Res."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"a1655","DOI":"10.1136\/bmj.a1655","article-title":"Developing and evaluating complex interventions: the new Medical Research Council guidance.","volume":"337","author":"P Craig","year":"2008","journal-title":"BMJ."},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.6084\/m9.figshare.30112093.v1","article-title":"GAMBOL STUDY patient information sheets and consent forms.","author":"S Criseno","year":"2025","journal-title":"figshare."}],"container-title":["NIHR Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-83\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-83\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-83\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T15:29:13Z","timestamp":1787153353000},"score":1,"resource":{"primary":{"URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-83\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,19]]},"references-count":25,"URL":"https:\/\/doi.org\/10.3310\/nihropenres.14030.2","relation":{"has-version":[{"id-type":"doi","id":"10.3310\/nihropenres.14030.1","asserted-by":"subject"}]},"ISSN":["2633-4402"],"issn-type":[{"value":"2633-4402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,19]]},"assertion":[{"value":"Indexed","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-83\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.3310\/nihropenres.15259.r37317, Giorgio Sodero, Universita Cattolica del Sacro Cuore, Rome, Lazio, 30 Sep 2025, version 1, indexed","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-83\/v1#referee-response-37317","order":0,"name":"referee-response-37317","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Sherwin Criseno<\/b>; \n<i>Posted: 30 Sep 2025<\/i>; Dear Dr. Sodero,  Thank you for your very useful comments and suggestions. We will update the manuscript to incorporate your suggestions.&nbsp;  Kind regard,  Sherwin Criseno","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-83\/v2#referee-comment-3488","order":1,"name":"referee-comment-3488","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.3310\/nihropenres.15259.r37460, Daniel Morganstein, Chelsea and Westminster NHS Foundation Trust, Imperial College London, London, 10 Nov 2025, version 1, indexed","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-83\/v1#referee-response-37460","order":2,"name":"referee-response-37460","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.3310\/nihropenres.15259.r37466, Rob Murray, Leeds Teaching Hospital NHS Trust, Leeds, 17 Nov 2025, version 1, indexed","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-83\/v1#referee-response-37466","order":3,"name":"referee-response-37466","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Sherwin Criseno<\/b>; \n<i>Posted: 06 Aug 2026<\/i>; Thank you Prof. Murray for your comments which we have considered.  Comment 1 \n<i>Following the Plain Language Summary only Phase 1 is qualified. The plain language summaries of Phase 2 and Phase 3 appear to be missing.<\/i>  \n<b>We thank the reviewer for highlighting this point. The descriptions of Phases 2 and 3 are included within the Plain Language Summary; however, we agree that the formatting may not have made this sufficiently clear. We have revised the section to ensure that all three phases are clearly presented and consistently described for ease of understanding by patients and members of the public.<\/b>  Comment 2 \n<i>How would analysis of data from phase 1 account for variable experience of specialists completing the questionnaire?<\/i>  \n<b>We thank the reviewer for this important observation. The primary purpose of Phase 1 is to obtain a broad understanding of current UK clinical practice rather than estimate prevalence or generate weighted national estimates. We have clarified that respondents will be asked to report the approximate number of adults with GHD managed within their service. This information will be used descriptively to contextualise responses and explore potential differences according to centre size and level of experience where appropriate.<\/b>  Comment 3 \n<i>Is LDL-cholesterol directly measured, or calculated?<\/i>  \n<b>We thank the reviewer for highlighting this point. LDL cholesterol will be calculated using the standard laboratory methodology. This has now been clarified in the protocol.<\/b>  Comment 4 \n<i>Group 3 refers to the discontinuation group (Group 2). Should this be Group 1?<\/i>  \n<b>We thank the reviewer for identifying this typographical error. The discontinuation group is Group 1 and the protocol has been corrected accordingly.<\/b>  Comment 5 \n<i>Methodology for body composition measures and blood sampling is repeated across visits.<\/i>  \n<b>We agree with the reviewer. To improve readability and reduce duplication, the detailed methodology for anthropometric measurements, blood sampling and DXA assessment has been described at Visit 1, with subsequent visits referring back to the same methodology where appropriate.<\/b>  Comment 6 \n<i>Would it be interesting to invite patients who declined participation in Phase 2?<\/i>  \n<b>We agree that the perspectives of patients who decline participation could provide valuable insights into barriers to recruitment and trial acceptability. However, the primary objective of Phase 3 is to explore experiences of participation, retention and withdrawal from the feasibility study. Given the scope of the current project and available resources, interviews are restricted to individuals who enrolled in Phase 2. We acknowledge that exploring the views of trial decliners would be an important area for future research.<\/b>  Comment 7 \n<i>Should other hormone replacement therapies be stable before recruitment? How will changes be monitored? Should weight-loss drugs be excluded?<\/i>  \n<b>We thank the reviewer for these valuable suggestions. We agree that changes in other hormone replacement therapies could potentially influence study outcomes. We have therefore clarified that participants should be receiving stable replacement doses where clinically appropriate prior to enrolment, and that all adjustments to concomitant hormone therapies during follow-up will be recorded and considered during data analysis. <\/b>  Comment 8 \n<i>Should Group 3 undergo an additional assessment or DXA scan at the time of transfer?<\/i>  \n<b>We thank the reviewer for this suggestion. Patients transferring to Group 3 will continue study follow-up according to the existing visit schedule. We considered performing an additional assessment at the time of transfer; however, this would increase participant burden and radiation exposure without directly contributing to the primary feasibility objectives. The timing of treatment re-initiation, reasons for withdrawal, symptoms and relevant clinical outcomes will be recorded as part of ongoing monitoring.<\/b>  Comment 9 \n<i>There are a number of typographical errors which require addressing.<\/i>  Comment 1 \n<i>Following the Plain Language Summary only Phase 1 is qualified. The plain language summaries of Phase 2 and Phase 3 appear to be missing.<\/i> \n<b>We thank the reviewer for highlighting this point. The descriptions of Phases 2 and 3 are included within the Plain Language Summary; however, we agree that the formatting may not have made this sufficiently clear. We have revised the section to ensure that all three phases are clearly presented and consistently described for ease of understanding by patients and members of the public.<\/b>  Comment 2 \n<b>Reviewer comment:<\/b> \n<i>How would analysis of data from phase 1 account for variable experience of specialists completing the questionnaire?<\/i> \n<b>We thank the reviewer for this important observation. The primary purpose of Phase 1 is to obtain a broad understanding of current UK clinical practice rather than estimate prevalence or generate weighted national estimates. We have clarified that respondents will be asked to report the approximate number of adults with GHD managed within their service. This information will be used descriptively to contextualise responses and explore potential differences according to centre size and level of experience where appropriate.<\/b>  Comment 3 \n<i>Is LDL-cholesterol directly measured, or calculated?<\/i> \n<b>We thank the reviewer for highlighting this point. LDL cholesterol will be calculated using the standard laboratory methodology. This has now been clarified in the protocol.<\/b> Comment 4 \n<i>Group 3 refers to the discontinuation group (Group 2). Should this be Group 1?<\/i> \n<b>We thank the reviewer for identifying this typographical error. The discontinuation group is Group 1 and the protocol has been corrected accordingly.<\/b> Comment 5 \n<i>Methodology for body composition measures and blood sampling is repeated across visits.<\/i> We agree with the reviewer. To improve readability and reduce duplication, the detailed methodology for anthropometric measurements, blood sampling and DXA assessment has been described at Visit 1, with subsequent visits referring back to the same methodology where appropriate.  Comment 6 \n<i>Would it be interesting to invite patients who declined participation in Phase 2?<\/i> \n<b>We agree that the perspectives of patients who decline participation could provide valuable insights into barriers to recruitment and trial acceptability. However, the primary objective of Phase 3 is to explore experiences of participation, retention and withdrawal from the feasibility study. Given the scope of the current project and available resources, interviews are restricted to individuals who enrolled in Phase 2. We acknowledge that exploring the views of trial decliners would be an important area for future research.<\/b>  Comment 7 \n<i>Should other hormone replacement therapies be stable before recruitment? How will changes be monitored? Should weight-loss drugs be excluded?<\/i> \n<b>We thank the reviewer for these valuable suggestions. We agree that changes in other hormone replacement therapies could potentially influence study outcomes. We have therefore clarified that participants should be receiving stable replacement doses where clinically appropriate prior to enrolment, and that all adjustments to concomitant hormone therapies during follow-up will be recorded and considered during data analysis. <\/b>  Comment 8 \n<i>Should Group 3 undergo an additional assessment or DXA scan at the time of transfer?<\/i> \n<b>We thank the reviewer for this suggestion. Patients transferring to Group 3 will continue study follow-up according to the existing visit schedule. We considered performing an additional assessment at the time of transfer; however, this would increase participant burden and radiation exposure without directly contributing to the primary feasibility objectives. The timing of treatment re-initiation, reasons for withdrawal, symptoms and relevant clinical outcomes will be recorded as part of ongoing monitoring.<\/b>  Comment 9 \n<i>There are a number of typographical errors which require addressing.<\/i> We thank the reviewer for highlighting this issue. The manuscript has undergone a further detailed review for spelling, grammar, formatting and typographical errors. All identified errors have been corrected in the revised version.","URL":"https:\/\/openresearch.nihr.ac.uk\/articles\/5-83\/v2#referee-comment-3618","order":4,"name":"referee-comment-3618","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This project is funded by the National Institute for Health and Care Research (NIHR301571) under its Clinical Doctoral Research Fellowship (NIHR CDRF). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The funders had no role in study design, and will not have any role in data collection, data management, interpretation, report writing nor the decision to submit the report for publication.\r\n\r\nThe funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":5,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}