Opioids and Their Endocrine Effects: A Systematic Review and Meta-analysis

J Clin Endocrinol Metab. 2020 Mar 1;105(3):1020-1029. doi: 10.1210/clinem/dgz022.


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 (CI). 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, 3250 patients, 99.5% males). Prevalence of hypocortisolism relying on dynamic and nondynamic 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 one-fifth of all patients. Periodical evaluation of at least the gonadal and adrenal axes is therefore advisable.

Keywords: analgesics; hypocortisolism; hypogonadism; opioids; pituitary.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Analgesics, Opioid / adverse effects*
  • Chronic Pain / drug therapy*
  • Chronic Pain / pathology
  • Endocrine System Diseases / chemically induced
  • Endocrine System Diseases / pathology*
  • Humans
  • Hypogonadism / chemically induced
  • Hypogonadism / pathology*
  • Pituitary Hormones / metabolism
  • Prognosis


  • Analgesics, Opioid
  • Pituitary Hormones