204
Views
0
CrossRef citations to date
0
Altmetric
Persepective

Opioid-induced hypogonadism in opioid use disorder, its role in negative reinforcement, and implications for treatment and retention

ORCID Icon &
Pages 132-138 | Received 14 Sep 2023, Accepted 03 Dec 2023, Published online: 06 Feb 2024

References

  • Products - vital statistics rapid release - provisional drug overdose data [Internet]. 2023 [accessed 2023 Aug 9]. https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm.
  • De Maeyer J, Vanderplasschen W, Broekaert E. Quality of life among opiate-dependent individuals: a review of the literature. Int J Drug Policy. 2010;21:364–80. doi:10.1016/j.drugpo.2010.01.010.
  • Degenhardt L, Grebely J, Stone J, Hickman M, Vickerman P, Marshall BDL, Bruneau J, Altice FL, Henderson G, Rahimi-Movaghar A, et al. Global patterns of opioid use and dependence: population harms, interventions, and future action. Lancet Lond Engl. 2019;394:1560–79. doi:10.1016/S0140-6736(19)32229-9.
  • Williams AR, Johnson KA, Thomas CP, Reif S, Socías ME, Henry BF, Neighbors C, Gordon AJ, Horgan C, Nosyk B, et al. Commentary article: opioid use disorder cascade of care framework design: a roadmap. Subst Abuse. 2022;43:1207–14. doi:10.1080/08897077.2022.2074604.
  • Williams AR, Mauro CM, Feng T, Wilson A, Cruz A, Olfson M, Crystal S, Samples H, Chiodo L. Performance measurement for opioid use disorder medication treatment and care retention. Am J Psychiatry. 2023;180:454. doi:10.1176/appi.ajp.20220456.
  • Shurman J, Koob GF, Gutstein HB. Opioids, pain, the brain, and Hyperkatifeia: a framework for the rational use of opioids for pain. Pain Med Malden Mass. 2010;11:1092–98. doi:10.1111/j.1526-4637.2010.00881.x.
  • Koob GF. Neurobiology of opioid addiction: opponent process, hyperkatifeia, and negative reinforcement. Biol Psychiatry. 2020;87:44–53. doi:10.1016/j.biopsych.2019.05.023.
  • Vuong C, Van Uum SHM, O’Dell LE, Lutfy K, Friedman TC. The effects of opioids and opioid analogs on animal and human endocrine systems. Endocr Rev. 2010;31:98–132. doi:10.1210/er.2009-0009.
  • Fountas A, Chai ST, Kourkouti C, Karavitaki N. Mechanisms of endocrinology: endocrinology of opioids. Eur J Endocrinol. 2018;179:R183–96. doi:10.1530/EJE-18-0270.
  • de Vries F, Bruin M, Lobatto DJ, Dekkers OM, Schoones JW, van Furth WR, Pereira AM, Karavitaki N, Biermasz NR, Zamanipoor Najafabadi AH. Opioids and their endocrine effects: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2020;105:1020–29. doi:10.1210/clinem/dgz022.
  • Hallinan R, Byrne A, Agho K, McMahon CG, Tynan P, Attia J. Hypogonadism in men receiving methadone and buprenorphine maintenance treatment. Int J Androl. 2009;32:131–39. doi:10.1111/j.1365-2605.2007.00824.x.
  • Yee A, Loh HS, Danaee M, Riahi S, Ng CG, Sulaiman AH. Plasma testosterone and sexual function in Southeast Asian men receiving methadone and buprenorphine maintenance treatment. J Sex Med. 2018;15:159–66. doi:10.1016/j.jsxm.2017.12.004.
  • Zitzmann M. Testosterone, mood, behaviour and quality of life. Andrology. 2020;8:1598–605. doi:10.1111/andr.12867.
  • Bhasin S, Brito JP, Cunningham GR, Hayes FJ, Hodis HN, Matsumoto AM, Snyder PJ, Swerdloff RS, Wu FC, Yialamas MA, et al. Testosterone therapy in men with hypogonadism: an endocrine society* clinical practice guideline. J Clin Endocrinol Metab. 2018;103:1715–44. doi:10.1210/jc.2018-00229.
  • Coluzzi F, Billeci D, Maggi M, Corona G. Testosterone deficiency in non-cancer opioid-treated patients. J Endocrinol Invest. 2018;41:1377–88. doi:10.1007/s40618-018-0964-3.
  • Corona G, Goulis DG, Huhtaniemi I, Zitzmann M, Toppari J, Forti G, Vanderschueren D, Wu FC. European Academy of Andrology (EAA) guidelines on investigation, treatment and monitoring of functional hypogonadism in males. Andrology. 2020;8:970–87. doi:10.1111/andr.12770.
  • Indirli R, Lanzi V, Arosio M, Mantovani G, Ferrante E . The association of hypogonadism with depression and its treatments. Front Endocrinol (Lausanne). 2023;14:1198437. doi:10.3389/fendo.2023.1198437.
  • Shores MM, Moceri VM, Sloan KL, Matsumoto AM, Kivlahan DR. Low testosterone levels predict incident depressive illness in older men: effects of age and medical morbidity. J Clin Psychiatry. 2005;66:7–14. doi:10.4088/JCP.v66n0102.
  • Wu FCW, Tajar A, Beynon JM, Pye SR, Silman AJ, Finn JD, O’Neill TW, Bartfai G, Casanueva FF, Forti G, et al. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med. 2010;363:123–35. doi:10.1056/NEJMoa0911101.
  • Shahinian VB, Kuo YF, Freeman JL, Goodwin JS. Risk of the “androgen deprivation syndrome” in men receiving androgen deprivation for prostate cancer. Archives Int Med. 2006;166(4):465–71. doi:10.1001/.465.
  • Schneider G, Nienhaus K, Gromoll J, Heuft G, Nieschlag E, Zitzmann M. Depressive symptoms in men aged 50 years and older and their relationship to genetic androgen receptor polymorphism and sex hormone levels in three different samples. Am J Geriatr Psychiatry Off J Am Assoc Geriatr Psychiatry. 2011;19:274–83. doi:10.1097/JGP.0b013e3181e70c22.
  • Hunt GE, Malhi GS, Cleary M, Lai HMX, Sitharthan T. Prevalence of comorbid bipolar and substance use disorders in clinical settings, 1990–2015: systematic review and meta-analysis. J Affect Disord. 2016;206:331–49. doi:10.1016/j.jad.2016.07.011.
  • Saha S, Lim CC, Degenhardt L, Cannon DL, Bremner M, Prentis F, Lawrence Z, Heffernan E, Meurk C, Reilly J, et al. Comorbidity between mood and substance-related disorders: a systematic review and meta-analysis. Aust N Z J Psychiatry. 2022;56:757–70. doi:10.1177/00048674211054740.
  • Crum RM, Green KM, Amin-Esmaeili M, Susukida R, Mojtabai R, Storr CL, Riehm KE, Young AS, Reboussin BA. The role of mood disorders in the progression of and recovery from alcohol and drug use problems: a latent transition analysis. Drug Alcohol Depend. 2022;238:109566. doi:10.1016/j.drugalcdep.2022.109566.
  • Esmaeelzadeh S, Moraros J, Thorpe L, Bird Y. Examining the association and directionality between mental health disorders and substance use among adolescents and young adults in the U.S. and Canada—A systematic review and meta-analysis. J Clin Med. 2018;7:543. doi:10.3390/jcm7120543.
  • McGrath JJ, Lim CCW, Plana-Ripoll O, Holtz Y, Agerbo E, Momen NC, Mortensen PB, Pedersen CB, Abdulmalik J, Aguilar-Gaxiola S, et al. Comorbidity within mental disorders: a comprehensive analysis based on 145 990 survey respondents from 27 countries. Epidemiol Psychiatr Sci. 2020;29:e153. doi:10.1017/S2045796020000633.
  • Greiner MG, Shulman M, Scodes J, Choo TH, Pavlicova M, Opara O, Campbell ANC, Novo P, Fishman M, Lee JD, et al. Patient characteristics associated with opioid abstinence after participation in a trial of buprenorphine versus injectable naltrexone. Subst Use Misuse. 2022;57:1732–42.
  • Hasin D, Liu X, Nunes E, McCloud S, Samet S, Endicott J. Effects of major depression on remission and relapse of substance dependence. Arch Gen Psychiatry. 2002;59:375–80. doi:10.1001/archpsyc.59.4.375.
  • Samet S, Fenton MC, Nunes E, Greenstein E, Aharonovich E, Hasin D. Effects of independent and substance-induced major depressive disorder on remission and relapse of alcohol, cocaine and heroin dependence. Addict Abingdon Engl. 2013;108:115–23. doi:10.1111/j.1360-0443.2012.04010.x.
  • Amanatkar HR, Chibnall JT, Seo BW, Manepalli JN, Grossberg GT. Impact of exogenous testosterone on mood: a systematic review and meta-analysis of randomized placebo-controlled trials. Ann Clin Psychiatry Off J Am Acad Clin Psychiatr. 2014;26:19–32.
  • Elliott J, Kelly SE, Millar AC, Peterson J, Chen L, Johnston A, Kotb A, Skidmore B, Bai Z, Mamdani M, et al. Testosterone therapy in hypogonadal men: a systematic review and network meta-analysis. BMJ Open. 2017;7:e015284.
  • Walther A, Breidenstein J, Miller R. Association of testosterone treatment with alleviation of depressive symptoms in men: a systematic review and meta-analysis. JAMA Psychiarty. 2019;76:31–40. doi:10.1001/jamapsychiatry.2018.2734.
  • Zarrouf FA, Artz S, Griffith J, Sirbu C, Kommor M. Testosterone and depression: systematic review and meta-analysis. J Psychiatr Pract. 2009;15:289. doi:10.1097/01.pra.0000358315.88931.fc.
  • Athnaiel O, Cantillo S, Paredes S, Knezevic NN. The role of sex hormones in pain-related conditions. Int J Mol Sci. 2023;24:1866. doi:10.3390/ijms24031866.
  • Maurer AJ, Lissounov A, Knezevic I, Candido KD, Knezevic NN. Pain and sex hormones: a review of current understanding. Pain Manag. 2016;6:285–96. doi:10.2217/pmt-2015-0002.
  • Chen SC, Chang TJ, Wu FS. Competitive inhibition of the capsaicin receptor-mediated current by dehydroepiandrosterone in rat dorsal root ganglion neurons. J Pharmacol Exp Ther. 2004;311:529–36. doi:10.1124/jpet.104.069096.
  • Craft RM. Modulation of pain by estrogens. PAIN. 2007 Nov;132:S3. doi:10.1016/j.pain.2007.09.028.
  • Malkin CJ, Pugh PJ, Jones RD, Kapoor D, Channer KS, Jones TH. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab. 2004;89:3313–18. doi:10.1210/jc.2003-031069.
  • Norata GD, Tibolla G, Seccomandi PM, Poletti A, Catapano AL. Dihydrotestosterone decreases tumor necrosis factor-alpha and lipopolysaccharide-induced inflammatory response in human endothelial cells. J Clin Endocrinol Metab. 2006;91:546–54. doi:10.1210/jc.2005-1664.
  • Larson MJ, Paasche-Orlow M, Cheng DM, Lloyd-Travaglini C, Saitz R, Samet JH. Persistent pain is associated with substance use after detoxification: a prospective cohort analysis. Addict Abingdon Engl. 2007;102:752–60. doi:10.1111/j.1360-0443.2007.01759.x.
  • Compton PA, Wasser TE, Cheatle MD. Increased experimental pain sensitivity in chronic pain patients who developed opioid use disorder. Clin J Pain. 2020;36:667–74. doi:10.1097/AJP.0000000000000855.
  • Glintborg D, Vaegter HB, Christensen LL, Bendix E, Graven-Nielsen T, Andersen PG, Andersen M. Testosterone replacement therapy of opioid-induced male hypogonadism improved body composition but not pain perception: a double-blind, randomized, and placebo-controlled trial. Eur J Endocrinol. 2020;182:539–48. doi:10.1530/EJE-19-0979.
  • Grönbladh A, Nylander E, Hallberg M. The neurobiology and addiction potential of anabolic androgenic steroids and the effects of growth hormone. Brain Res Bull. 2016;126:127–37. doi:10.1016/j.brainresbull.2016.05.003.
  • Johnson LR, Wood RI. Oral testosterone self-administration in male hamsters. Neuroendocrinology. 2001;73:285–92. doi:10.1159/000054645.
  • Parrilla-Carrero J, Figueroa O, Lugo A, García-Sosa R, Brito-Vargas P, Cruz B, Rivera M, Barreto-Estrada JL. The anabolic steroids testosterone propionate and nandrolone, but not 17α-methyltestosterone, induce conditioned place preference in adult mice. Drug Alcohol Depend. 2009;100:122–27. doi:10.1016/j.drugalcdep.2008.09.014.
  • Wood RI, Johnson LR, Chu L, Schad C, Self DW. Testosterone reinforcement: intravenous and intracerebroventricular self-administration in male rats and hamsters. Psychopharmacol (Berl). 2004;171:298–305. doi:10.1007/s00213-003-1587-7.
  • Kanayama G, Hudson JI, Pope HG. Illicit anabolic–androgenic steroid use. Horm Behav. 2010;58:111–21. doi:10.1016/j.yhbeh.2009.09.006.
  • Kanayama G, Hudson JI, DeLuca J, Isaacs S, Baggish A, Weiner R, Bhasin S, Pope HG. Prolonged hypogonadism in males following withdrawal from anabolic–androgenic steroids: an under-recognized problem. Addiction. 2015;110:823–31. doi:10.1111/add.12850.
  • Kanayama G, Hudson JI, Pope HG. Features of men with anabolic-androgenic steroid dependence: a comparison with nondependent AAS users and with AAS nonusers. Drug Alcohol Depend. 2009;102:130–37. doi:10.1016/j.drugalcdep.2009.02.008.
  • Kritzer M. The distribution of immunoreactivity for intracellular androgen receptors in the cerebral cortex of hormonally intact adult male and female rats: localization in pyramidal neurons making corticocortical connections. Cereb Cortex. 2004;14:268–80. doi:10.1093/cercor/bhg127.
  • Kritzer MF, Creutz LM. Region and sex differences in constituent dopamine neurons and immunoreactivity for intracellular estrogen and androgen receptors in mesocortical projections in rats. J Neurosci. 2008;28:9525–35. doi:10.1523/JNEUROSCI.2637-08.2008.
  • Low KL, Ma C, Soma KK. Tyramide signal amplification permits immunohistochemical analyses of androgen receptors in the rat prefrontal cortex. J Histochem Cytochem. 2017;65:295–308. doi:10.1369/0022155417694870.
  • Aubele T, Kritzer MF. Gonadectomy and hormone replacement affects in vivo basal extracellular dopamine levels in the prefrontal cortex but not motor cortex of adult male rats. Cereb Cortex. 2011;21:222–32. doi:10.1093/cercor/bhq083.
  • Tobiansky DJ, Wallin-Miller KG, Floresco SB, Wood RI, Soma KK. Androgen regulation of the mesocorticolimbic system and executive function. Front Endocrinol. 2018;9:279. doi:10.3389/fendo.2018.00279.
  • Nelson CJ, Lee JS, Gamboa MC, Roth AJ. Cognitive effects of hormone therapy in men with prostate cancer: a review. Cancer. 2008;113:1097–106. doi:10.1002/cncr.23658.
  • Tan S, Sohrabi HR, Weinborn M, Tegg M, Bucks RS, Taddei K, Carruthers M, Martins RN. Effects of testosterone supplementation on separate cognitive domains in cognitively healthy older men: a meta-analysis of Current randomized clinical trials. Am J Geriatr Psychiatry Off J Am Assoc Geriatr Psychiatry. 2019;27:1232–46. doi:10.1016/j.jagp.2019.05.008.
  • Laudet AB. The case for considering quality of life in addiction research and clinical practice. Addict Sci Clin Pract. 2011;6:44–55. doi:10.1136/bmj.b2495.
  • Laudet AB, Becker JB, White WL. Don’t wanna go through that madness no more: quality of life satisfaction as predictor of sustained remission from illicit drug Misuse. Subst Use Misuse. 2009;44:227–52. doi:10.1080/10826080802714462.
  • Zhou K, Wang D, Li H, Wei X, Yin J, Liang P, Kou L, Hao M, You L, Li X, et al. Bidirectional relationships between retention and health-related quality of life in Chinese mainland patients receiving methadone maintenance treatment. PLoS ONE. 2017;12:e0179009. doi:10.1371/journal.pone.0179009.
  • Raheem OA, Patel SH, Sisul D, Furnish TJ, Hsieh TC. The role of testosterone supplemental therapy in opioid-induced hypogonadism: a retrospective pilot analysis. Am J Mens Health. 2017;11:1208–13. doi:10.1177/1557988316672396.
  • Basaria S, Travison TG, Alford D, Knapp PE, Teeter K, Cahalan C, Eder R, Lakshman K, Bachman E, Mensing G, et al. Effects of testosterone replacement in men with opioid-induced androgen deficiency: a randomized controlled trial. Pain. 2015;156:280–88. doi:10.1097/01.j.pain.0000460308.86819.aa.
  • Blick G, Khera M, Bhattacharya RK, Nguyen D, Kushner H, Miner MM. Testosterone replacement therapy outcomes among opioid users: the Testim Registry in the United States (TRiUS). Pain Med Malden Mass. 2012;13:688–98. doi:10.1111/j.1526-4637.2012.01368.x.
  • Aloisi AM, Ceccarelli I, Carlucci M, Suman A, Sindaco G, Mameli S, Paci V, Ravaioli L, Passavanti G, Bachiocco V, et al. Hormone replacement therapy in morphine-induced hypogonadic male chronic pain patients. Reprod Biol Endocrinol RBE. 2011;9:26. doi:10.1186/1477-7827-9-26.
  • Daniell HW, Lentz R, Mazer NA. Open-label pilot study of testosterone patch therapy in men with opioid-induced androgen deficiency. J Pain. 2006;7:200–10. doi:10.1016/j.jpain.2005.10.009.
  • Degenhardt L, Clark B, Macpherson G, Leppan O, Nielsen S, Zahra E, Larance B, Kimber J, Martino-Burke D, Hickman M, et al. Buprenorphine versus methadone for the treatment of opioid dependence: a systematic review and meta-analysis of randomised and observational studies. Lancet Psychiatry. 2023;10:386–402. doi:10.1016/S2215-0366(23)00095-0.
  • Bliesener N, Albrecht S, Schwager A, Weckbecker K, Lichtermann D, Klingmüller D. Plasma testosterone and sexual function in men receiving buprenorphine maintenance for opioid dependence. J Clin Endocrinol Metab. 2005;90:203–06. doi:10.1210/jc.2004-0929.
  • Fruzzetti F, Bersi C, Parrini D, Ricci C, Genazzani AR. Effect of long-term naltrexone treatment on endocrine profile, clinical features, and insulin sensitivity in obese women with polycystic ovary syndrome. Fertil Steril. 2002;77:936–44. doi:10.1016/S0015-0282(02)02955-2.
  • Limonta P, Wayne Bardin C, Hahn EF, Thau RB. Unexpected effects of nalmefene, a new opiate antagonist, on the hypothalamic-pituitary-gonadal axis in the male rat. Steroids. 1985;46:955–65. doi:10.1016/S0039-128X(85)80003-9.
  • Mello NK, Mendelson JH, Kelly M. Acute effects of nalmefene on LH, prolactin, and testosterone in male rhesus monkeys. Pharmacol Biochem Behav. 2000;66:275–83. doi:10.1016/S0091-3057(00)00190-8.
  • Mendelson JH, Mello NK. Plasma testosterone levels during chronic heroin use and protracted astinence. A study of Hong Kong addicts. Clin Pharmacol Ther. 1975;17:529–33. doi:10.1002/cpt1975175529.
  • Mendelson JH, Mendelson JE, Patch VD. Plasma testosterone levels in heroin addiction and during methadone maintenance. J Pharmacol Exp Ther. 1975;192:211–17.
  • Sordo L, Barrio G, Bravo MJ, Indave BI, Degenhardt L, Wiessing L, Ferri M, Pastor-Barriuso R. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. BMJ. 2017;357:j1550. doi:10.1136/bmj.j1550.
  • Huhn AS, Hobelmann JG, Oyler GA, Strain EC. Protracted renal clearance of fentanyl in persons with opioid use disorder. Drug Alcohol Depend. 2020;214:108147. doi:10.1016/j.drugalcdep.2020.108147.
  • Santen FJ, Sofsky J, Bilic N, Lippert R. Mechanism of action of narcotics in the production of menstrual dysfunction in women. Fertil Steril. 1975;26:538–48. doi:10.1016/S0015-0282(16)41173-8.
  • Wersocki E, Bedson J, Chen Y, LeResche L, Dunn KM. Comprehensive systematic review of long-term opioids in women with chronic noncancer pain and associated reproductive dysfunction (hypothalamic–pituitary–gonadal axis disruption). PAIN. 2017;158:8. doi:10.1097/j.pain.0000000000000691.
  • Bangasser DA, Valentino RJ. Sex differences in stress-related psychiatric disorders: neurobiological perspectives. Front Neuroendocrinol. 2014;35:303–19. doi:10.1016/j.yfrne.2014.03.008.
  • Mogil JS. Sex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon. Nat Rev Neurosci. 2012;13:859–66. doi:10.1038/nrn3360.
  • Presto P, Mazzitelli M, Junell R, Griffin Z, Neugebauer V. Sex differences in pain along the neuraxis. Neuropharmacology. 2022;210:109030. doi:10.1016/j.neuropharm.2022.109030.
  • Kundakovic M, Rocks D. Sex hormone fluctuation and increased female risk for depression and anxiety disorders: from clinical evidence to molecular mechanisms. Front Neuroendocrinol. 2022;66:101010. doi:10.1016/j.yfrne.2022.101010.
  • Hudson A, Stamp JA. Ovarian hormones and propensity to drug relapse: a review. Neurosci Biobehav Rev. 2011;35:427–36. doi:10.1016/j.neubiorev.2010.05.001.
  • Becker JB, Koob GF, Gottesman MM. Sex differences in animal models: focus on addiction. Pharmacol Rev. 2016 ;68:242–63. doi:10.1124/pr.115.011163.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.