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.

Mapping the Steroid Response to Major Trauma from Injury to Recovery: A Prospective Cohort Study

“…Interestingly, we observed a differential impact of the cumulative opioid dose on adrenal and gonadal androgens, respectively, with a significantly delayed recovery of DHEA and DHEAS, but a trend towards faster recovery of gonadal testosterone synthesis in patients with higher cumulative opioid doses. Previous data on opioid effects on adrenal androgen production are very scarce, but our findings with respect to gonadal testosterone biosynthesis contrasted previous studies describing suppressive opioid effects on the HPG axis (41,42).…”

“…Interestingly, patients on higher opioid doses showed a higher early peak in cortisol production after trauma, followed by persistently lower circulating cortisol during the recovery period, as compared with patients on lower opioid doses. Previous reports have described suppressive effects of opioids on the HPA axis, though studies in smaller mammals have indicated an acute stimulatory effect of opioid administration on serum cortisol concentrations (41,42).…”

Effect of antipsychotics on breast tumors by analysis of the Japanese Adverse Drug Event Report database and cell-based experiments

“…These are the limitations of the research. In addition to antipsychotics, H 2 blockers, tricyclic antidepressants, SSRIs, antihypertensives, estrogen therapy, and opioids [ 18 – 22 ] among others, are known factors in drug-induced hyperprolactinemia. Therefore, concomitant medications may also have an impact in individual cases.…”

Testosterone Use in Adolescent Males: Current Practice and Unmet Needs

“…Eating disorders and excessive exercise may result in decreased activity of the hypothalamic-pituitary-gonadal axis and hypogonadism [ 52 , 53 ]. Finally, the number of adolescent males who experience hypogonadism because of opioid addiction or androgen abuse, although uncertain, is likely significant [ 54 ].…”