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Opioid-induced endocrinopathy (OIE) is a complication of chronic opioid treatment.^[1]^[2]^[3] It is a common name for all hypothalamo-pituitary axis disorders, which can be observed mostly after long term use of opioids, both as a treatment and as a substance of abuse.^[1]

The effect of opioids on hormonal levels can be measured immediately after the application of the opioid.^[1] The onset of deficit mostly comes after longer time of use of high doses, but sometimes coexisting factor like cancer disease,^[4]^[5] pain disease or other medicines may accelerate the progress.^[1]

Pathophysiology

Opioid-induced hypogonadism, caused by negative effect of opioids on hypothalamo-pituitary gonadal axis is most often ( 21-86% of opioid users).^[6] Hypogonadism is induced through direct inhibitory action of opioids on receptors within the hypothalamic–pituitary–gonadal (HPG) and hypothalamic–pituitary–adrenal (HPA) axes as well as testosterone production within the testes.^[6] Opioid-induced hypogonadism and direct negative effect of opioids to bone formatting leads to osteoporosis.^[1]

The opioid effect on adrenal hormone production, somatostatin and thyroid levels is less common, but should be considered as well due to the serious impact on the patients' total health.^[1]

Effect on hypothalamic–pituitary–adrenal axis is well described both after short acting and long-acting treatment with opioids, resulting in cortisol deficit. It might lead to the problems in stress situations, immunodeficiency and Addison crisis.^[1]

Opioid-induced hyperprolactemia can lead to the painful growth of breast (gynecomastia), milk production (galactorhea) and hypogonadism.^[1]

Opioid-induced defect of hypothalamic–pituitary–somatotropic axis leads to growth hormone deficiency which in adults results in cognitive dysfunction, mainly affecting visuospatial memory and orientation.^[7]

Symptoms

Testosterone deficit at men leads to erectile problems, infertility, depression, anxiety, night sweat and hot flushes. Premenopausal women due to the low estrogen levels struggle of irregular menstruation, infertility or complete menopause. Postmenopausal women might have lower levels of dehydroxyepiandosterone, LH and FSH as well leading to fatigue and depressions.^[1] Fatigue, higher incidence of infection diseases, problems with wound healing and total exhaustion during infects or Addison crisis are symptoms of cortisol deficit.^[1] Pathological fractures in early age at opioid users must indicate bone density evaluation and osteoporosis suspicion.^[1] Disorientation in the previously well-known surrounding can be the symptom of GH deficit.^[7]

Treatment

If cessation or decreasing of doses of opioids is possible, endocrinopathy can be reversed. If the treatment with opioid cannot be disrupted due to the serious reasons, for example in substitution program or due to the severe pain or cancer, the hormonal substitution should be considered.^[1] It seems like opioids with partial antagonistic action, like buprenorphine, affect hormonal levels less.^[1]

References

^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m Fountas, Athanasios; Chai, Shu Teng; Kourkouti, Chrysoula; Karavitaki, Niki (October 2018). "MECHANISMS OF ENDOCRINOLOGY: Endocrinology of opioids". European Journal of Endocrinology. 179 (4): R183 – R196. doi:10.1530/EJE-18-0270. ISSN 0804-4643. PMID 30299887.
^ Colameco, Stephen; Coren, Joshua S. (January 2009). "Opioid-induced endocrinopathy". The Journal of the American Osteopathic Association. 109 (1): 20–25. ISSN 1945-1997. PMID 19193821.
^ Rhodin, Annica; Stridsberg, Mats; Gordh, Torsten (June 2010). "Opioid Endocrinopathy: A Clinical Problem in Patients With Chronic Pain and Long-term Oral Opioid Treatment". The Clinical Journal of Pain. 26 (5): 374–380. doi:10.1097/AJP.0b013e3181d1059d. ISSN 0749-8047. PMID 20473043. S2CID 30105241.
^ Buss, Tomasz; Leppert, Wojciech (February 2014). "Opioid-Induced Endocrinopathy in Cancer Patients: An Underestimated Clinical Problem". Advances in Therapy. 31 (2): 153–167. doi:10.1007/s12325-014-0096-x. ISSN 0741-238X. PMID 24497073. S2CID 207417731.
^ Merdin, Alparslan; Merdin, Fatma Avci; Gündüz, Şeyda; Bozcuk, Hakan; Coşkun, Hasan Şenol (May 2016). "Opioid endocrinopathy: A clinical problem in patients with cancer pain". Experimental and Therapeutic Medicine. 11 (5): 1819–1822. doi:10.3892/etm.2016.3156. ISSN 1792-0981. PMC 4840782. PMID 27168810.
^ ^a ^b Coluzzi, F.; Billeci, D.; Maggi, M.; Corona, G. (December 2018). "Testosterone deficiency in non-cancer opioid-treated patients". Journal of Endocrinological Investigation. 41 (12): 1377–1388. doi:10.1007/s40618-018-0964-3. ISSN 1720-8386. PMC 6244554. PMID 30343356.
^ ^a ^b Rhodin, A.; von EHREN, M.; Skottheim, B.; Grönbladh, A.; Ortiz-Nieto, F.; Raininko, R.; Gordh, T.; Nyberg, F. (July 2014). "Recombinant human growth hormone improves cognitive capacity in a pain patient exposed to chronic opioids: GH improves cognition in pain patient". Acta Anaesthesiologica Scandinavica. 58 (6): 759–765. doi:10.1111/aas.12309. PMC 4265204. PMID 24712862.