OBJECTIVE: The increased use of opioids has resulted in an unprecedented opioid epidemic. It is known that chronic opioid use affects the activity of the gonadal axis, but the frequency of this and other pituitary hormone deficiencies remains unclear. The aim of this systematic review and meta-analysis was to systematically review the effect of exogenous opioids on endocrine function. METHODS: Eight electronic databases were searched in May 2018 for randomized/observational studies assessing endocrine function in patients using opioids. A random effects model meta-analysis was performed to obtain weighted proportions of hypogonadism and hypocortisolism with a 95% confidence interval. RESULTS: 71 articles were included describing 13.949 patients, consisting of pain patients (n=34 studies), patients on maintenance treatment for opioid addiction (n=17) and healthy volunteers (n=5) with similar opioid effects between these groups. Morphine (n=17) was mostly used, followed by methadone (n=15) and opioid dose defined as morphine equivalent daily dose (n=14), with no difference in effects between groups.  Based on 15 studies (3.250 patients, %male: 99.5) on chronic opioids, the prevalence of hypogonadism was 65% (95% CI: 57-73). Based on 5 studies (207 patients, %male: 57.5), the prevalence of hypocortisolism, based on non-dynamic testing, was 23% (95% CI: 12-35). The systematic review showed an increasing trend for serum prolactin concentrations, and no clear effects on the somatotropic (n=5) and thyrotropic axes (n=7). Six studies reported that testosterone replacement in opioid induced hypogonadism increases testosterone levels, but clinical effects were not reported. CONCLUSION: Hypogonadism occurs in more than half of male chronic opioid users, and hypocortisolism in nearly a quarter of all patients. Periodical evaluation of the gonadal and adrenal axes is mandatory  in these patients. More studies are needed on the effects of chronic opioid use on the female gonadal axis and the other endocrine axes, also focusing on experienced symptoms and symptom management.