Hormone Replacement Therapy for Restoring the HPG Axis in Pain Patients Treated with Long-Term Opioid Analgesics

DOI: 10.4236/pp.2018.911036, PP. 473-480

Keywords: Opioid Therapy, Chronic Pain, HPG Axis, Hormone Replacement Therapy

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Abstract:

Opioids are a treatment option for a variety of chronic pain conditions. But long-term opioid use can be associated with side effects, including hypogonadism. Opioid-induced hypogonadism (OIhG) is associated with the alteration of the hypothalamic-pituitary-gonadal axis (HPG). In males, hypogonadism can result in erectile dysfunction, reduced libido, fatigue, worsening mood, and increased risk of osteoporosis; in females, it can result in changes in the menstrual cycle and reduced libido, among other effects. A current treatment option for these patients is hormone replacement therapy. In this report, we discuss the problem of opioid-induced hypogonadism, and the therapeutic approach and the potential complications of treating pain patients using hormone replacement therapy.

References

[1]	Manchikanti, L., Vallejo, R., Manchikanti, K.N., Benyamin, R.M., Datta, S. and Christo, P.J. (2011) Effectiveness of Long-Term Opioid Therapy for Chronic Non-Cancer Pain. Pain Physician, 14, E133-E156. https://www.ncbi.nlm.nih.gov/pubmed/21412378
[2]	Furlan, A.D., Sandoval, J.A., Mailis-Gagnon, A. and Tunks, E. (2006) Opioids for Chronic Noncancer Pain: A Meta-Analysis of Effectiveness and Side Effects. Canadian Medical Association Journal, 174, 1589-1594. https://www.ncbi.nlm.nih.gov/pubmed/16717269 https://doi.org/10.1503/cmaj.051528
[3]	Benyamin, R., et al. (2008) Opioid Complications and Side Effects. Pain Physician, 11, S105-S120. https://www.ncbi.nlm.nih.gov/pubmed/18443635
[4]	Ceccarelli, I., De Padova, A.M., Fiorenzani, P., Massafra, C. and Aloisi, A.M. (2006) Single Opioid Administration Modifies Gonadal Steroids in Both the CNS and Plasma of Male Rats. Neuroscience, 140, 929-937. https://www.ncbi.nlm.nih.gov/pubmed/16580783 https://doi.org/10.1016/j.neuroscience.2006.02.044
[5]	Ceccarelli, I., Rossi, A., Maddalena, M., Weber, E. and Aloisi, A.M. (2009) Effects of Morphine on Testosterone Levels in Rat C6 Glioma Cells: Modulation by Anastrozole. Journal of Cellular Physiology, 221, 1-4. https://doi.org/10.1002/jcp.21830 https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.21830
[6]	Amini, H. and Ahmadiani, A. (2005) In Vivo Evidence for an Increase in 5 Alpha-Reductase Activity in the Rat Central Nervous System Following Morphine Exposure. International Journal of Developmental Neuroscience, 23, 621-626. https://kundoc.com/pdf-in-vivo-evidence-for-an-increase-in-5alpha-reductase-activity-in-the-rat-central.html https://doi.org/10.1016/j.ijdevneu.2005.07.001
[7]	Abs, R., et al. (2000) Endocrine Consequences of Long-Term Intrathecal Administration of Opioids. Journal of Clinical Endocrinology and Metabolism, 85, 2215-2222. https://www.ncbi.nlm.nih.gov/pubmed/10852454 https://doi.org/10.1210/jcem.85.6.6615
[8]	Aloisi, A.M., et al. (2005) Gender-Related Effects of Chronic Non-Malignant Pain and Opioid Therapy on Plasma Levels of Macrophage Migration Inhibitory Factor (MIF). Pain, 115, 142-151. https://www.ncbi.nlm.nih.gov/pubmed/15836977 https://doi.org/10.1016/j.pain.2005.02.019
[9]	Daniell, H.W. (2002) Hypogonadism in Men Consuming Sustained-Action Oral Opioids. Journal of Pain, 3, 377-384. https://doi.org/10.1054/jpai.2002.126790 https://www.ncbi.nlm.nih.gov/pubmed/14622741
[10]	Daniell, H.W. (2008) Opioid Endocrinopathy in Women Consuming Prescribed Sustained-Action Opioids for Control of Nonmalignant Pain. Journal of Pain, 9, 28-36. https://www.ncbi.nlm.nih.gov/pubmed/17936076 https://doi.org/10.1016/j.jpain.2007.08.005
[11]	Fraser, L.A., et al. (2009) Oral Opioids for chronic Non-Cancer Pain: Higher Prevalence of Hypogonadism in Men than in Women. Experimental and Clinical Endocrinology & Diabetes, 117, 38-43. https://www.ncbi.nlm.nih.gov/pubmed/18523930 https://doi.org/10.1055/s-2008-1076715
[12]	Azizi, F., Vagenakis, A.G, Longcope, C., Ingbar, S.H. and Braverman, L.E. (1973) Decreased Serum Testosterone Concentration in Male Heroin and Methadone Addicts. Steroids, 22, 467-472. https://doi.org/10.1016/0039-128X(73)90002-0
[13]	Mendelson, J.H., Ellingboe, J., Judson, B.A. and Goldstein, A. (1984) Plasma Testosterone and Luteinizing Hormone Levels during Levo-Alpha-Acetylmethadol Maintenance and Withdrawal. Clinical Pharmacology & Therapeutics, 35, 545-547. https://doi.org/10.1038/clpt.1984.75
[14]	Woody, G., McLellan, A.T., O’Brien, C., Persky, H., Stevens, G., Arndt, I. and Carroff, S. (1988) Hormone Secretion in Methadone-Dependent and Abstinent Patients. NIDA Research Monograph, 81, 216-223.
[15]	Roberts, L.J., Finch, P.M., Pullan, P.T., Bhagat, C.I. and Price, L.M. (2002) Sex Hormone Suppression by Intrathecal Opioids: A Prospective Study. Clinical Journal of Pain, 18, 144-148. https://www.ncbi.nlm.nih.gov/pubmed/12048415 https://doi.org/10.1097/00002508-200205000-00002
[16]	Vestergaard, P., Rejnmark, L. and Mosekilde, L. (2006) Fracture Risk Associated with the Use of Morphine and Opiates. Journal of Internal Medicine, 260, 76-87. https://www.ncbi.nlm.nih.gov/pubmed/16789982 https://doi.org/10.1111/j.1365-2796.2006.01667.x
[17]	Moffat, S.D., et al. (2004) Free Testosterone and Risk for Alzheimer Disease in Older Men. Neurology, 62, 188-193. https://www.ncbi.nlm.nih.gov/pubmed/14745052 https://doi.org/10.1212/WNL.62.2.188
[18]	Straub, R.H. and Cutolo, M. (2001) Involvement of the Hypothalamic-Pituitary-Adrenal/Gonadal Axis and the Peripheral Nervous System in Rheumatoid Arthritis: Viewpoint Based on a Systemic Pathogenetic Role. Arthritis & Rheumatology, 44, 493-507. https://www.ncbi.nlm.nih.gov/pubmed/11263762 https://doi.org/10.1002/1529-0131(200103)44:3<493::AID-ANR95>3.0.CO;2-U
[19]	Vuong, C., Van Uum, S.H., O’Dell, L.E., Lutfy, K. and Friedman, T.C. (2010) The Effects of Opioids and Opioid Analogs on Animal and Human Endocrine Systems. Endocrine Reviews, 31, 98-132. https://www.ncbi.nlm.nih.gov/pubmed/19903933
[20]	Osran, H., et al. (1993) Adrenal Androgens and Cortisol in Major Depression. American Journal of Psychiatry, 150, 806-809. https://doi.org/10.1176/ajp.150.5.806
[21]	Seidman, S.N. and Walsh, B.T. (1999) Testosterone and Depression in Aging Men. The American Journal of Geriatric Psychiatry, 7, 18-33. https://www.ncbi.nlm.nih.gov/pubmed/9919317 https://doi.org/10.1097/00019442-199902000-00004
[22]	Zarrouf, F.A., Artz, S., Griffith, J., Sirbu, C. and Kommor, M. (2009) Testosterone and Depression: Systematic Review and Meta-Analysis. Journal of Psychiatric Practice, 15, 289-305. https://www.ncbi.nlm.nih.gov/pubmed/19625884 https://doi.org/10.1097/01.pra.0000358315.88931.fc
[23]	Daniell, H.W., Lentz, R. and Mazer, N.A. (2006) Open-Label Pilot Study of Testosterone Patch Therapy in Men with Opioid-Induced Androgen Deficiency. The Journal of Pain, 7, 200-210. https://www.ncbi.nlm.nih.gov/pubmed/16516826 https://doi.org/10.1016/j.jpain.2005.10.009
[24]	Aloisi, A.M., et al. (2011) Hormone Replacement Therapy in Morphine-Induced Hypogonadic Male Chronic Pain Patients. Reproductive Biology and Endocrinology, 9, 26. https://doi.org/10.1186/1477-7827-9-26

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