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This study aimed at investigating associations between L\u2010TOT and clinical outcomes including sustained attention, short\u2010term and working memory, worst pain intensity, sleep quality, mood, and health\u2010related quality of life in patients with chronic non\u2010cancer pain (CNCP). Additionally, the study aimed at exploring whether endocrine biomarkers mediate the relationship between L\u2010TOT and these outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Cross\u2010sectional study with 82 adult CNCP patients divided into two groups (opioid treated (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200938) and controls not treated with opioids (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200944)). Linear regression analyses assessed associations between L\u2010TOT, outcome variables, and the mediating effects of endocrine biomarkers.\n                    <\/jats:p>\n                    <jats:p>A Bootstrap approach with 95% confidence intervals was applied to analyse the natural indirect effect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The opioid group had worse sleep quality (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.018), physical functioning (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0186), social functioning (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002), and higher pain intensity (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) compared with controls. Men in the L\u2010TOT group experienced worse measures for the same variables, and additionally for anxiety (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.028), depression (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.040), role physical (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.038), role emotional (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), fatigue (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.019), and emotional well\u2010being (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001). Only the association between L\u2010TOT and anxiety in men was significantly mediated by total testosterone (\u03b2\u2009=\u20091.6, Bias\u2010Corrected Bootstrap 95% CI: 0.1; 4.1,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.045).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CNCP patients in L\u2010TOT showed significantly poorer outcomes than controls. Only testosterone mediated anxiety in men, indicating a natural indirect effect. Causality and mediating effects of endocrine biomarkers need to be further explored, but the associations are an alert to the potential effects of opioids.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>This study reveals the broader health impacts of opioid use, particularly the role of hormone\u2010related factors in men, which may be linked to specific adverse effects and consequences. Investigating these hormonal dynamics could lead to improved treatment strategies and outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejp.70027","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T06:19:13Z","timestamp":1745907553000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Opioid Therapy in Chronic Pain: Assessment of Clinical Outcomes and Relationships With Endocrine Biomarkers"],"prefix":"10.1002","volume":"29","author":[{"given":"Dalia","family":"Abou\u2010Kassem","sequence":"first","affiliation":[{"name":"Multidisciplinary Pain Centre, Department of Neuroanaesthesiology, Pain and Respiratory Support Rigshospitalet Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pernille","family":"D\u00f8ssing Kwateng Diasso","sequence":"additional","affiliation":[{"name":"Department of Surgery 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