The endocrine effects of opioids used for the management of persistent pain are poorly understood by clinicians and patients, and hormone levels are rarely measured. It is recognized that opioids exert this effect via the hypothalamic-pituitary-gonadal axis. Additional effects on adrenal hormones, weight, blood pressure and bone density may also occur. Symptoms and signs of sex hormone deficiency occur in both men and women but are under-reported and are often clinically unrecognized.
The potential effects of long term opioid therapy on the endocrine system should be explained to patients before opioid therapy is commenced. Monitoring of sex hormones is recommended; if there are deficiencies opioids should be tapered and withdrawn, if this is clinically acceptable.
If opioid therapy has to continue, hormone replacement therapy should be initiated and monitored by an endocrinologist.
MooreARMcQuayHJ. Prevalence of opioid adverse events in chronic nonmalignant pain: systematic review of randomised trials of oral opioids. Arthritis Res Ther2005; 7: 1046–1051.
2.
FurlanADSandovalJAMailis-GagnonA. Opioids for chronic non-cancer pain: a meta-analysis of effectiveness and side effects. Can Med Assoc J2006; 174: 1589–1594.
3.
RaghavanSHarveyADHumbleSR. New opioid side effects and implications for long-term therapy. Trends Anaesth Crit Care2011; 1: 18–21.
4.
OkieS. A flood of opioids, a rising tide of deaths. N Engl J Med2010; 363(21): 1981–1983.
5.
GravesRHForty Years in China, Baltimore: Woodward, 1895.
6.
Cumming HS, Control of DrugAddiction Mainly a Police Problem, The American City Magazine (November1925, file 126, box 3, sub-series 1, series 3.
7.
KatzNMazerNA. The impact of opioids on the endocrine system. Clin J Pain2009; 25(2): 170–175.
8.
BruceCA. Report on the manufacture of tea and on the extent and produce of the tea plantations in Assam. Calcutta : Bishop’s College Press, 1839.
9.
Hiller-SturmhofelSBartkeA. The endocrine system: An overview. Alcohol Health Res World1998; 22(3): 153–164.
10.
GanongWF. Review of medical physiology. USA: Lange/McGraw-Hill, 2005.
11.
Luo Xiwentr. Bencao Gangmu: Compendium of Materia Medica. Foreign Languages Press, 2003. First published 1578
12.
Van VugtDABabyNStewartMReidRL. The paradoxical stimulatory effect of morphine on LH secretion is dose-dependent and naloxone-reversible. Neuroendocrinology1989; 50: 109–116.
13.
De la RosaREHennesseyJV. Hypogonadism and methadone: hypothalamic hypogonadism after long-term use of high-dose methadone. Endocr Pract1996; 2:4–7.
14.
DaniellHW. DHEAS deficiency during consumption of sustained-action prescribed opioids: evidence for opioid-induced inhibition of adrenal androgen production. J Pain2006; 7(12): 901–907.
15.
VuongCVan UumSHMO’DellL. The effects of opioids and opioid analogs on animal and human endocrine systems. Endocr Rev2010; 31(1): 98–132.
16.
Van FurthWRvan EmstMGvan ReeJM. Opioids and sexual behaviour of male rats: involvement of the medial preoptic area. Behav Neurosci1995; 109; 123–134.
17.
DaniellHarry WThe Endocrine Society’s clinical guidelines on testosterone therapy in adult men with androgen deficiency syndromes. J Clin Endocrinol Metab2010; 95(6): 2536–2559.
18.
O’DonneABAraujoABMcKinlayJB. The health of normally aging men: The Massachusetts Male Aging Study (1987–2004). Exp Gerontol2004; (7): 975–984.
19.
KatzN. The impact of opioids on the endocrine system. Pain Management Rounds2005; 1(9). www.painmanagementrounds.org (accessed 5 February 2012)
20.
FaccinettiFGrassoAPetragliaF. Impaired circadian rhythmicity of β-lipotrophin, β-endorphin and ACTH in heroin addicts. Acta Endocrinol1984; 105(2): 149–155.
21.
DaniellHW. Opioid endocrinopathy in women consuming prescribed sustained-action opioids for control of non-malignant pain. J Pain2008; 9(1): 28–36.
22.
ThosaniSJiminezC. Opioid-induced biochemical alterations of the neuroendocrine axis. Expert Rev Endocrinol Metab2011; 6(5): 705–713.
23.
AbsRVerhelstJMaeyaertJ. Endocrine consequences of long-term intrathecal administration of opioids. J Clin Endo Metab2000; 85(6): 2215–2222.
24.
SarretDLe BerreJPZemraouiN. Tramadol-induced hyponatraemia. Am J Kidney Dis2008; 52(5): 1026.
25.
LindowSWHendricksMSNugentFA. Morphine suppresses the oxytocin response in breast-feeding women. Gynecol Obstet Invest1999; 48(1): 33–37.
KapoorDGoodwinEChannerKSJonesTH. Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol2006; 154: 899–906.
28.
Opioids for persistent pain; good practice. 2010The British Pain Society, Faculty of Pain Medicine of the Royal College of Anaesthetists, Royal College of General Practitioners and the Faculty of Addiction Medicines of the Royal College of Psychiatrists. Available at: http://www.britishpainsociety.org/book_opioid_main.pdf (accessed 5 February 2012)
29.
RobertsLJFinchPMPullanPT. Sex hormone suppression by intrathecal opioids: a prospective study. Clin J Pain2002; 18: 144–148.
30.
ThimineurMAKravitzEVodapallyMS. Intrathecal opioid treatment for chronic non-malignant pain: a 3-year prospective study. Pain2004; 109: 242–249.
31.
RajagopalAVassilopoulou-SellinRPalmerJL. Symptomatic hypogonadism in male survivors of cancer with chronic exposure to opioids. Cancer2004; 100(4): 851–858.
