The Effect of Opioid Therapy on Endocrine Function
Section snippets
Comorbidities Associated With Hypogonadism
Pain typically does not occur absent underlying illness, injury, or other comorbidities. Indeed, pain pathophysiology, pain comorbidities, opioid dosage, and patient age, and several other factors can be direct causes of or contributors to hypogonadism. The Hypogonadism in Males (HIM) study demonstrated a relation between hypogonadism and several comorbid conditions.12 Ninety-five primary care practices assessed hypogonadism within a population of 2162 men aged ≥45 years regardless of the
Opioid Effects on the Hypothalamic-Pituitary-Gonadal Axis
Opioids have a well-documented effect on 2 endocrine systems.2, 18, 19 The first is the hypothalamic-pituitary-gonadal axis. In the normally functioning system, gonadotropin-releasing hormone (GnRH) is released by the hypothalamus and targets the pituitary gland, which is then stimulated to produce luteinizing hormone (LH) and follicle-stimulating hormone (FSH).2 These hormones enter the systemic circulation and stimulate the end organs of the axis—the testes or ovaries—to respectively produce
Effect of Opioids on the Hypothalamic-Pituitary-Adrenal Axis
The hypothalamic-pituitary-adrenal axis is another endocrine system that can be affected by opioids.18 The cascade for this system is initiated with the release of corticotropin-releasing hormone (CRH) from the hypothalamus, targeting the pituitary. The pituitary is then stimulated to release adrenocorticotropic hormone (ACTH), which enters the systemic circulation and induces the adrenal glands to produce 2 hormones, cortisol and dehydroepiandrosterone (DHEA). Cortisol is important for
Monitoring and Treatment
Standards have not been established for monitoring and treating opioid-induced hypogonadism or hypoadrenalism. Based on the literature and clinical experience, however, patients taking opioid therapy equivalent to ≥100 mg of morphine daily should be monitored for the development of hypogonadism.18 Patients may not necessarily report symptoms of hypogonadism, such as sexual dysfunction, menstrual irregularities, or fatigue. Therefore, monitoring should include specific questioning regarding
Summary
Managing opioid-induced endocrine dysfunction in clinical practice begins with monitoring for symptoms, coupled with appropriate diagnostic tests, in all patients taking long-term opioids. Nonopioid analgesic approaches and/or opioid rotation should be considered in the management of opioid-induced endocrine dysfunction. Furthermore, when supported by a risk-benefit analysis and with appropriate consultation, hormone supplementation may be an option for certain individuals.
Author Disclosures
The author of this article has disclosed the following industry relationships:
Michael J. Brennan, MD, consultant: Covidien, Endo Pharmaceuticals Inc, Purdue Pharma; speakers bureau: Covidien, Endo Pharmaceuticals Inc, inSYS Therapeutics Inc, Johnson & Johnson, Purdue Pharma, Teva/Cephalon; stockholder: Apricus Biosciences, Inc., Pfizer Inc, Teva Pharmaceuticals, Zalicus.
Acknowledgments
Research and editorial support was provided by Miller Medical Communications, LLC, and by Rebecca A Bachmann, PhD, of BookishProse.
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