Opioid-induced endocrinopathies
Open accessAbstract
The use of opioids is becoming a global epidemic, leading to a rise in the occurrence and recognition of the effects of opioid drugs on the endocrine system. Nonetheless, opioid-induced endocrinopathies still remain underdiagnosed, mainly because of symptom under-reporting by patients and poor clinician awareness. Hypogonadism is the most well recognised consequence of opioid use, but the inhibitory effects of opioid drugs on the hypothalamo-pituitary-adrenal axis and their negative effects on bone health also require attention. Hyperprolactinaemia might be detected in opioid users, but clinically relevant thyroid dysfunction has not been identified. The effects of opioids on other hormones have not been clearly defined. Assessment of gonadal and adrenal function (particularly if high index of clinical suspicion of hypogonadism or hypoadrenalism) and evaluation of bone health are advised in people that use opiods. Discontinuation or reduction of opioid dose and appropriate hormone replacement are the management approaches that should be considered for hypogonadism and hypoadrenalism. Further research is needed to facilitate the development of evidence-based guidelines on the diagnosis and optimal management of opioid-induced endocrinopathies.
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Studies evaluating the effects of opioids on the GH axis in humans are limited and data supporting a robust and consistent effect are insufficient.
“Studies evaluating the effects of opioids on the GH axis in humans are limited and data supporting a robust and consistent effect are insufficient (70).”
From Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement (2024) · cites this paper as [70]
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Research works printed but not linked: 4
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- In clinical practice, opioids are primarily used as analgesic agents. Although μ-receptor is the main target for opioid analgesics, δ-and κ-receptors also regulate pain and analgesia; 11 the involvement of NOP receptor is under investigation. 12 Some types (codeine, morphine and methadone) are also used in chronic cough (especially in patients with lung cancer), 13 whilst some μ-receptor agonists (loperamide, codeine) and mixed opioid receptor agonists/antagonists are used for diarrhoea-predominant irritable bowel syndrome. 14 Morphine has been used for a long time to relieve pain, dyspnoea and anxiety in patients with acute myocardial infarction or pulmonary oedema but, nowadays, its use has been significantly decreased due to possible elevated morbidity and mortality risk in these patients. 15,16 Finally, heroin is used as a recreational drug due to its euphoric effects. The following We used the search terms were used: " "opioid"", "opiate", "opioid agonist", "opiate agonist", "opium", "morphine", "heroin", "diamorphine", "dihydromorphine", "ethylmorphine", "azidomorphine", "normorphine", "hydromorphone", "oxymorphone", "pentamorphone", "morphinone", "codeine", "hydrocodone", "oxycodone", "methadone", "isomethadone", "tramadol", "desmetramadol", "fentanyl", "carfentanil", "buprenorphine"or "opiate", "alfentanil", "remifentanil", "pentazocine", "pethidine", "meperidine" in combination with each of the terms "pituitary", "hypopituitarism", "androgen", "androgen deficiency", "hypogonadism", "gonadotropin", "testosterone", "oligomenorrhoea", "amenorrhoea", "sexual dusfunction", "fertility", "adrenal", "adrenal insufficiency", "hypoadrenalism", "adrenal crisis", "cortisol", "hypocotisolism", "hypocortisolaemia", "growth hormone", "insulin-like growth factor 1", "prolactin", "hyperprolactinaemia", "thyroid", "TSH", "hypothyroidism", "hyperthyroidism", "vasopressin", "antidiuretic hormone", "oxytocin", "bones", "osteopenia", "osteoporosis", "bone mineral density" and "fracture"endocrine" or "endocrinopathy". We gave priority for inclusion to relevant scientific literature published from 2013 onwards, although selected key older references are also cited. We also searched the reference lists of articles identified by this search strategy and selected those we judged relevant. Review articles are cited to provide readers with more details and more references than this Review has room for. Legends for figures
Cited by
Sorted by citations
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“3,13,183 Using corticosteroids or metoclopramide may also cause hypogonadism.”
Opioids for chronic pain management in patients with dialysis-dependent kidney failure
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“As well, long-term use of opioids may influence the immune system (by reducing immune competence [3]) and the endocrine system (by creating hypogonadism and hypoadrenalism [4]).”
BackgroundBremelanotide for Treatment of Female Hypoactive Sexual Desire
Edinoff, A. N., Sanders, N. M., Lewis, K. B., Apgar, T. L., Cornett, E. M., Kaye, A. M., & Kaye, A. D. (2022) · Neurology International · doi:10.3390/neurolint14010006 · Cited by 38 · see citing works
“Opioids can inhibit ovarian sex hormones and adrenal androgen production, which was found in a study that looked at women who were chronically using sustained-action opioids [22,23].”
BackgroundIatrogenic adrenal insufficiency in adults
Martin‐Grace, J., Tomkins, M., O’Reilly, M., & Sherlock, M. (2024) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00929-x · Cited by 34 · see citing works
“The time interval between reduction or discontinuation of opioids and recovery of the HPA axis has not been established 158,172 .”
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“Despite the opioid epidemic, chronic opioid use in large subpopulations, and the widespread use of medication-assisted treatments for opioid rehabilitation which require prolonged exposure to opioids, opioid-induced endocrinopathies remain under-diagnosed and underappreciated [6].”
BackgroundPolimanti, R. A., Levey, D. F., Pathak, G. A., Wendt, F. R., Nuñez, Y. Z., Ursano, R. J., Kessler, R. C., Kranzler, H. R., Stein, M. B., & Gelernter, J. E. (2021) · Translational Psychiatry · doi:10.1038/s41398-020-01153-1 · Cited by 23 · see citing works
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Exogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement
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“Although not every reduction in cortisol is clinically relevant and warrants full workup for OAI, a high index of suspicion is prudent for patients treated with high-dose opioids and/or for prolonged periods (7).”
BackgroundDrug-induced osteoporosis and mechanisms of bone tissue regeneration through trace elements
da Costa, N. D. S., Lima, L. S., Galiciolli, M. E. A., Ribeiro, D. H. F., Ribeiro, M. M., Garica, G. D. P. J., Marçal, I. S., da Silva, J. F., Pereira, M. E., Oliveira, C. S., et al. (2024) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/j.jtemb.2024.127446 · Cited by 11 · see citing works
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“10 11–13 Although opioids remain a crucial analgesic in clinical settings, 14 the global opioid crisis and side effects 15,16 require collaborative efforts to optimize perioperative nonopioid analgesic strategies.”
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Problems with opioids - beyond misuse
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- Authors
- Fountas, A., Van Uum, S., & Karavitaki, N.
- Affiliations
- University Hospitals Birmingham NHS Foundation Trust (GB)
- Corresponding author
- Karavitaki, Niki
- Venue
- The Lancet Diabetes & Endocrinology
- Publisher
- Elsevier BV
- Published
- 2020-01
- Volume
- 8
- Issue
- 1
- Pages
- 68-80
- ISSN
- 2213-8587 (ISSN-L)
- OpenAlex
- W2953324257
- Semantic Scholar
- 458d754fbd66ab7612d4ce532f01456d861d25f5
- Cited by
- 77
- References
- 148
- Citations by year
- 2026: 16 · 2025: 13 · 2024: 10 · 2023: 7 · 2022: 12 · 2021: 14 · 2020: 5
- FWCI
- 1.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Lancet Diabetes & Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Keywords
- opioid use, hypogonadism, adrenal insufficiency, hypothalamic-pituitary-adrenal axis, hyperprolactinemia, bone health, thyroid dysfunction, hormone replacement therapy, underdiagnosis
- MeSH terms
- Analgesics, Opioid, Endocrine System Diseases, Humans, Hypogonadism, Hypothalamo-Hypophyseal System, Opioid-Related Disorders, Pituitary-Adrenal System, Hormone Replacement Therapy
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