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This systematic review and meta\u2010analysis aimed at investigating the published evidence of L\u2010TOT effects on the endocrine system in adult CNCP patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Databases and Data Treatment<\/jats:title><jats:p>A systematic search of the literature in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and the CINAHL was performed. Studies examining measures of endocrine function of the hypothalamic\u2010pituitary\u2010gonadal, \u2010adrenal, \u2010thyroid, \u2010somatotropic and \u2010prolactin axis in adult CNCP patients in L\u2010TOT (\u22654\u00a0weeks of use) were included. Outcomes and the level of evidence were analyzed (The Cochrane Collaboration Tool, modified version of the Newcastle\u2010Ottawa Scale and Rating of Recommendations Assessment, Development and Evaluation working group).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 2,660 studies were identified; 1981 excluded and finally thirteen studies (one randomized controlled trial (RCT), three longitudinal\u2010 and nine cross\u2010sectional studies) were analyzed. L\u2010TOT was associated with low insulin, suppression of the hypothalamic\u2010pituitary\u2010gonadal axis and alterations of the hypothalamic\u2010pituitary\u2010adrenal axis in both men and women with CNCP compared to different control groups (CNCP or healthy pain\u2010free). No other significant differences were reported. The studies had a high risk of bias and the overall quality of evidence was low.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>There seems to be an impact of L\u2010TOT in CNCP patients on several components of the endocrine system, but the level of evidence is weak. Given the high prevalence of L\u2010TOT use systematic studies of larger patient populations are urgently needed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>This systematic review and meta\u2010analysis suggested that long\u2010term opioid treatment may suppress the hypothalamic\u2010pituitary\u2010gonadal axis, and result in lower insulin levels and alter the glucocorticoid adrenal axis in adult chronic non\u2010cancer pain patients. This adds to the need of more research of both clinical and paraclinical outcomes and their association when initiating and maintaining long\u2010term opioid treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.1797","type":"journal-article","created":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T09:23:01Z","timestamp":1620897781000},"page":"1859-1875","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Long\u2010term opioid treatment and endocrine measures in chronic non\u2010cancer pain patients: A systematic review and meta\u2010analysis"],"prefix":"10.1002","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6458-754X","authenticated-orcid":false,"given":"Pernille D. 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