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

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.