Opioids and their endocrine effects: A systematic review and meta-analysis

Abstract

Context The increased use of opioids has resulted in an unprecedented opioid epidemic. Chronic opioid use causes hypogonadism, but its frequency, as well as the effects of opioids on other hypothalamo-pituitary-end organ hormone axes, remains unclear. Objective The aim of this systematic review and meta-analysis was to assess the effects of opioid use on pituitary function. Methods Eight electronic databases were searched for articles published up to May 8, 2018. Fixed- or random-effects meta-analysis was performed to estimate pooled proportions with 95% confidence intervals. This study is reported following the PRISMA- and MOOSE-guidelines. Data Synthesis 52 studies (22 low risk of bias) were included describing 18,428 subjects, consisting of patients with chronic pain (n=21 studies), or on maintenance treatment for opioid addiction (n=9) and healthy volunteers (n=4). The most frequently used opioid was methadone (n=13 studies), followed by morphine (n=12). Prevalence of hypogonadism was 63% (95% CI: 55-70%, 15 studies, 3,250 patients, 99.5% males). Prevalence of hypocortisolism relying on dynamic and non-dynamic testing was 15% (95% CI: 6-28%, 5 studies, 205 patients, 57.5% males) and including only studies using the insulin tolerance tests 24% (95% CI 16-33%, 2 studies, n=97 patients). In 5 out of 7 studies hyperprolactinemia was present. No clear effects on the somatotropic and hypothalamo-pituitary-thyroid axes were described. Conclusions Hypogonadism occurs in more than half of male opioid users, and hypocortisolism in approximately a fifth of all patients. Periodical evaluation of at least the gonadal and adrenal axes is therefore advisable.