Abstract

ContextThe 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.ObjectiveThe aim of this systematic review and meta-analysis was to assess the effects of opioid use on pituitary function.MethodsEight 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 synthesis52 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.ConclusionsHypogonadism 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.

Highlights

  • Over the past two decades, the use of opioids and the number of opioid-overdose related deaths has steadily increased [1]

  • One study using a health status questionnaire showed that chronic pain patients with opioidinduced hypocortisolism offered low-dose hydrocortisone replacement reported better scores on vitality and pain compared with the placebo group [33]

  • One study showed that patients with opioid exposure-related hypogonadism who received testosterone replacement had a lower reduction of bone mineral density (T-scores) compared to patients receiving placebo [-0.73 (SD 0.13) vs -1.61 (SD 0.23)] [37]

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Summary

METHODS

Eight electronic databases were searched for articles published up to May 8, 2018. Fixedor random-effects meta-analysis was performed to estimate pooled proportions with 95%. 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). 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
Introduction
Materials and methods
Adequate endocrine testing
Results
Discussion
Strengths and limitations
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