MECHANISMS OF ENDOCRINOLOGY: Endocrinology of opioids

Abstract

The use of opioids has grown substantially over the past two decades reaching the dimensions of a global epidemic. These drugs have effects on multiple levels of the endocrine system through mechanisms which are still not fully elucidated, and awareness of their endocrine sequelae is vital for all specialists prescribing or managing patients on them. Hypogonadism is the most well recognised consequence of opioid use (prevalence 21-86%) which, however, may remain undiagnosed with potential adverse outcomes for the patients. Although less frequent, cortisol deficiency can be also found. Furthermore, there is negative impact on bone health (with reduced bone mineral density and increased fracture risk) and occasionally hyperprolactinaemia, whereas the clinical significance of alterations in other hormones remains to be clarified. Discontinuation or reduction of the opioid and, in cases of chronic pain, consideration of alternative therapies for pain relief are potential management options. Hormonal replacement, especially when the above measures are not practically feasible, needs to be considered. Further studies are needed to clearly establish the prevalence of hormonal abnormalities with various regimes, doses and routes of opioids and to address reliably the long-term benefits and risks of hormonal treatment in patients on opioids. Until evidence-based, safe and cost-effective clinical guidelines become available, periodical assessment of the gonadal and adrenal function (particularly when relevant clinical manifestations are present) and evaluation of the bone health status are advised.

Hyperprolactinaemia

“…Opioids can cause hyperprolactinaemia mediated by µ-, κand δ-opioid receptors in the hypothalamus [65]. Acute oral or iv opioid administration can induce hyperprolactinaemia in men and post-menopausal women, while the findings after chronic opioid use have been mixed [65].…”

“…Opioids can cause hyperprolactinaemia mediated by µ-, κand δ-opioid receptors in the hypothalamus [65]. Acute oral or iv opioid administration can induce hyperprolactinaemia in men and post-menopausal women, while the findings after chronic opioid use have been mixed [65]. High PRL has been found in individuals with opioid addiction, with opium smoking and on oral opioids for chronic pain, but not with intrathecal morphine or opioid maintenance therapy with buprenorphine or methadone [65].…”

DIAGNOSIS OF ENDOCRINE DISEASE: Drug-induced endocrinopathies and diabetes: a combo-endocrinology overview

“…Studies on healthy human volunteers and on patients using opioids for therapeutic purposes or as medicationassisted addiction treatment or as a drug of abuse and dependence have shown their suppressive action on the hypothalamo-pituitary-gonadal (HPG) axis (53,54). The pathophysiological mechanism involves reduction of the release or disruption of the normal pulsatility of gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus, as well as decrease of the release of gonadotrophins from the pituitary gland and of testosterone or estradiol from the gonads (53,55). Negative effects of opioids on the kisspeptin-induced rise in the luteinizing hormone (LH) pulse amplitude may also be implicated (56).…”

“…Direct actions on the gonads have also been reported with reduction in the production of sperm, testicular interstitial fluid and intratesticular testosterone (57). The reported prevalence of hypogonadism ranges between 21 and 86% (55). The initial studies on this field involved heroin addicts and patients on methadone for maintenance and had shown decrease in testosterone levels in males, as well as reduction in LH and/or follicle-stimulating hormone (FSH) (58).…”

Undiscovered morphine. The effects of the long-term use of the opioids

“…Already after the first dose opioids inhibit the secretion of the pituitary gonadotrophins [20]. Prolonged opioid administration may lead to hypogonadism, as well in man as women [21][22][23]. Deficiency of testosterone and other sex hormones manifests itself as fatigue, anaemia, increased sensitivity to pain stimuli, muscular atrophy, osteoporosis, erectile and menstrual cycle dysfunction.…”