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 (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.

Figure 1.

Selection and screening of studies.

Figure 2.

Pooled percentage and sensitivity analysis, only including low risk of bias studies, of opioid exposure-related hypogonadism. It is important to note that 99.5% of the analyzed patients were males.

Figure 3.

Pooled percentage and sensitivity analysis, only including studies using ITT as assessment of the HPA axis, of opioid exposure-related hypocortisolism. Abbreviations: ITT, insulin tolerance test. HPA, hypothalamus–pituitary–adrenal.