Low Testosterone Among Males in Opioid Agonist Therapy and Its Association With Fatigue and Psychological Distress

Abstract Context Low testosterone levels are often considered an adverse effect of chronic opioid use. However, the prevalence of low testosterone levels and the association between testosterone levels and clinical symptoms among males receiving opioid agonist therapy (OAT) remain unclear. Objective To biochemically investigate the prevalence of low testosterone levels (free testosterone ≤0.22 nmol/L) and the association between free testosterone levels and symptoms of fatigue, measured using the 3-item Fatigue Severity scale, and psychological distress, measured using the 10-item Hopkins Symptoms Checklist. Design and Setting Prospective cohort study based on data collected between May 2017 and May 2024 from males receiving OAT recruited from OAT clinics at Haukeland University Hospital, Bergen, Norway. Participants 295 males aged 23 to 71 years, with a mean OAT duration of 8 years. Results A total of 236 (80%) of participants had low testosterone levels at baseline, and 108/148 (73%) had low testosterone levels in 2 consecutive measurements. No association was found between free testosterone and fatigue (baseline: coefficient: −1.0, 95% confidence interval: −6.4; 4.5, Δscore/year: 0.8, −5.2; 6.8) or between free testosterone and psychological distress (baseline: 0.4, −0.3; 1.0, Δscore/year: −0.1, −0.3; 0.2). Conclusion Eighty percent of males receiving OAT had low testosterone levels. However, testosterone levels were not associated with symptoms of fatigue or psychological distress. These findings should be interpreted with caution due to suboptimal power and potential influence of confounding. Further research is warranted to clarify the clinical significance of biochemical threshold values for low testosterone levels and their relationship to specific clinical symptoms in the OAT population.