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Licensed Unlicensed Requires Authentication Published by De Gruyter February 17, 2018

Impact of opioid therapy on gonadal hormones: focus on buprenorphine

  • Anjali Varma EMAIL logo , Mamta Sapra and Ali Iranmanesh

Abstract

Objective

The USA is in the midst of an opioid crisis. Understanding the impact of opioids and commonly used treatments for opioid dependence is essential for clinicians and researchers in order to educate and treat the nation’s growing population with opioid use disorders. As a relatively new treatment for opioid dependence, buprenorphine is gaining popularity to the extent of becoming not only a preferred approach to the maintenance of opiate addiction, but also an option for chronic pain management. The purpose of this report is to review the available evidence on the endocrine effects of buprenorphine, particularly as it relates to the hypothalamic-pituitary-gonadal (HPG) axis, which is controversial and not fully defined.

Method

We conducted a Pubmed search (2000–2017) for human studies in the English language for articles that were available as full length regarding buprenorphine, endocrinopathy, hypogonadism, bone density, opioids. Case reports were also reviewed, although prospective studies and randomized controlled trials received more weight.

Results

Opioid induced hypogonadism is well established. Most studies report that buprenorphine being a partial agonist/antagonist may not be impacting the pituitary trophic hormones as much. There are reports of sexual dysfunction in subjects maintained on buprenorphine, some without hormonal correlation. Thus with the understanding that pertinent clinical studies are limited in number, varied in methodology, mostly cross sectional, predominantly in men and small number of participants, more research in this area is warranted.

Conclusion

Based on a comprehensive review of the available literature, we conclude that despite its increasing popularity, buprenorphine has not been adequately studied in respect to its long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis. There is a great need for longitudinal systematic trials to define the potential buprenorphine-induced endocrine consequences.

Author Statement

  1. Research funding: Authors state no funding involved.

  2. Conflict of interest: Authors state no conflict of interest.

  3. Informed consent: Informed consent is not applicable.

  4. Ethical approval: The conducted research is not related to either human or animals use.

References

[1] NSDUH Report. America’s behavioral health-changes and challenges. 2016. www.SAMHSA.GOV/DATA.Search in Google Scholar

[2] Paulozzi LJ, Strickler GK, Kreiner PW, Koris CM; Centers for Disease Control and Prevention (CDC). Controlled substance prescribing patterns – prescription behavior surveillance system, Eight States, 2013. MMWR Surveill Summ. 2015;64:1–14.10.15585/mmwr.ss6409a1Search in Google Scholar

[3] Pasternak GW. The opiate receptors 2010. 2nd ed. New York, NY, USA: Humana Press; 2010. p. 23–48.Search in Google Scholar

[4] Pergolizzi J, Aloisi AM, Dahan A, Filitz J, Langford R, Likar R, et al. Current knowledge of buprenorphine and its unique pharmacological profile. Pain Pract. 2010;10:428–50.10.1111/j.1533-2500.2010.00378.xSearch in Google Scholar

[5] Ling W, Wesson DR. Clinical efficacy of buprenorphine: comparisons to methadone and placebo. Drug Alcohol Depend. 2003;70:S49–57.10.1016/S0376-8716(03)00059-0Search in Google Scholar

[6] Dunlap B, Cifu AS. Clinical management of opioid use disorder. J Am Med Assoc. 2016;316:338–9.10.1001/jama.2016.9795Search in Google Scholar

[7] Jones HE, Kaltenbach K, Heil SH, Stine SM, Coyle MG, Arria AM, et al. Neonatal abstinence syndrome after methadone or buprenorphine exposure. N Engl J Med. 2010;363:2320–31.10.1056/NEJMoa1005359Search in Google Scholar

[8] Sittl R, Griessinger N, Likar R. Analgesic efficacy and tolerability of transdermal buprenorphine in patients with inadequately controlled chronic pain related to cancer and other disorders: a multicenter, randomized, double-blind, placebo-controlled trial. Clin Ther. 2003;25:150–68.10.1016/S0149-2918(03)90019-1Search in Google Scholar

[9] Muriel C, Failde I, Micó JA, Neira M, Sánchez-Magro I. Effectiveness and tolerability of the buprenorphine transdermal system in patients with moderate to severe chronic pain: a multicenter, open-label, uncontrolled, prospective, observational clinical study. Clin Ther. 2005;27:451–62.10.1016/j.clinthera.2005.04.007Search in Google Scholar PubMed

[10] Cicero TJ, Bell RD, Wiest WG, Allison JH, Polakoski K, Robins E. Function of the male sex organs in heroin and methadone users. N Engl J Med. 1975;292:882–7.10.1056/NEJM197504242921703Search in Google Scholar PubMed

[11] Daniell HW. Opioid endocrinopathy in women consuming prescribed sustained-action opioids for control of nonmalignant pain. J Pain. 2008;9:28–36.10.1016/j.jpain.2007.08.005Search in Google Scholar PubMed

[12] Daniell HW. Hypogonadism in men consuming sustained-action oral opioids. J Pain. 2002;3:377–84.10.1054/jpai.2002.126790Search in Google Scholar PubMed

[13] Katz N, Mazer NA. The impact of opioids on the endocrine system. Clin J Pain. 2009;25:170–5.10.1097/AJP.0b013e3181850df6Search in Google Scholar PubMed

[14] Mendelson JH, Meyer RE, Ellingboe J, Mirin SM, McDougle M. Effects of heroin and methadone on plasma cortisol and testosterone. J Pharmacol Exp Ther. 1975;195:296–302.Search in Google Scholar

[15] Abs R, Verhelst J, Maeyaert J, Van Buyten JP, Opsomer F, Adriaensen H, et al. Endocrine consequences of long-term intrathecal administration of opioids. J Clin Endocrinol Metab. 2000;85:2215–22.10.1210/jcem.85.6.6615Search in Google Scholar PubMed

[16] Finch PM, Roberts LJ, Price L, Hadlow NC, Pullan PT. Hypogonadism in patients treated with intrathecal morphine. Clin J Pain. 2000;16:251–4.10.1097/00002508-200009000-00011Search in Google Scholar PubMed

[17] 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;90:203–6.10.1210/jc.2004-0929Search in Google Scholar PubMed

[18] Al-Gommer O, George S, Haque S, MoselhyH, Saravanappa T. Sexual dysfunction in male opiate users: a comparative study of heroin, methadone and buprenorphine. Addict Disord Treat. 2007;6:137–43.10.1097/ADT.0b013e31802b4e8cSearch in Google Scholar

[19] Hallinan R, Byrne A, Agho K, McMahon C, Tynan P, Attia J. Erectile dysfunction in men receiving methadone and buprenorphine maintenance treatment. J Sex Med. 2008;5:684–92.10.1111/j.1743-6109.2007.00702.xSearch in Google Scholar PubMed

[20] Quaglio G, Lugoboni F, Pattaro C, Melara B, Mezzelani P, Des Jarlais DC. Erectile dysfunction in male heroin users, receiving methadone and buprenorphine maintenance treatment. Drug Alcohol Depend. 2008;94:12–8.10.1016/j.drugalcdep.2007.09.025Search in Google Scholar PubMed

[21] Giacomuzzi SM, Khreis A, Riemer Y, Garber K, Ertl M. Buprenorphine and methadone maintenance treatment – sexual behaviour and dysfunction prevalence. Lett Drug Des Discov. 2009;6:13–13(1).10.2174/157018009787158580Search in Google Scholar

[22] Colameco S, Coren JS, Zimmerman DJ. Buprenorphine-induced symptomatic hypogonadism in men: case reports and discussion. J Addict Med. 2008;2:147–50.10.1097/ADM.0b013e318172d612Search in Google Scholar PubMed

[23] Ramdurg S, Ambekar A, Lal R. Sexual dysfunction among male patients receiving buprenorphine and naltrexone maintenance therapy for opioid dependence. J Sex Med. 2012;9:3198–204.10.1111/j.1743-6109.2011.02219.xSearch in Google Scholar PubMed

[24] Cioe PA, Friedmann PD, Stein MD. Erectile dysfunction in opioid users: lack of association with serum testosterone. J Addict Dis. 2010;29:455–60.10.1080/10550887.2010.509279Search in Google Scholar PubMed PubMed Central

[25] Aloisi AM, Aurilio C, Bachiocco V, Biasi G, Fiorenzani P, Pace MC, et al. Endocrine consequences of opioid therapy. Psychoneuroendocrinology. 2009;34:S162–8.10.1016/j.psyneuen.2009.05.013Search in Google Scholar PubMed

[26] Aurilio C, Ceccarelli I, Pota V, Sansone P, Massafra C, Barbarisi M, et al. Endocrine and behavioural effects of transdermal buprenorphine in pain-suffering women of different reproductive ages. Endocr J. 2011;58:1071–8.10.1507/endocrj.EJ11-0095Search in Google Scholar

[27] Fortin JD, Bailey GM, Vilensky JA. Does opioid use for pain management warrant routine bone mass density screening in men? Pain Physician. 2008;11:539–41.10.36076/ppj.2008/11/539Search in Google Scholar

[28] Kim TW, Alford DP, Malabanan A, Holick MF, Samet JH. Low bone density in patients receiving methadone maintenance treatment. Drug Alcohol Depend. 2006;85:258–62.10.1016/j.drugalcdep.2006.05.027Search in Google Scholar PubMed PubMed Central

[29] Coluzzi F, Pergolizzi J, Raffa RB, Mattia C. The unsolved case of “bone-impairing analgesics”: the endocrine effects of opioids on bone metabolism. Ther Clin Risk Manag. 2015;11:515–23.10.2147/TCRM.S79409Search in Google Scholar PubMed PubMed Central

[30] Facchinetti F, Grasso A, Petraglia F, Parrini D, Volpe A, Genazzani AR. Impaired circadian rhythmicity of beta-lipotrophin, beta-endorphin and ACTH in heroin addicts. Acta Endocrinol (Copenh). 1984;105:149–55.10.1530/acta.0.1050149Search in Google Scholar PubMed

[31] Van Uum SH, Sauvé B, Fraser LA, Morley-Forster P, Paul TL, Koren G. Elevated content of cortisol in hair of patients with severe chronic pain: a novel biomarker for stress. Stress. 2008;11:483–8.10.1080/10253890801887388Search in Google Scholar PubMed

[32] Camí J, Gilabert M, San L, de la Torre R. Hypercortisolism after opioid discontinuation in rapid detoxification of heroin addicts. Br J Addict. 1992;87:1145–51.10.1111/j.1360-0443.1992.tb02001.xSearch in Google Scholar PubMed

[33] Nava F, Caldiroli E, Premi S, Lucchini A. Relationship between plasma cortisol levels, withdrawal symptoms and craving in abstinent and treated heroin addicts. J Addict Dis. 2006;25:9–16.10.1300/J069v25n02_02Search in Google Scholar PubMed

[34] Pechnick RN, George R, Poland RE. The effects of the acute administration of buprenorphine hydrochloride on the release of anterior pituitary hormones in the rat: evidence for the involvement of multiple opiate receptors. Life Sci. 1985;37:1861–8.10.1016/0024-3205(85)90002-5Search in Google Scholar

[35] Félix NM, Leal RO, Goy-Thollot I, Walton RS, Gil SA, Mateus LM, et al. Effects of buprenorphine in the adrenal, thyroid, and cytokine intra-operative responses in a rat model (Rattus norvegicus): a preliminary study. Iran J Basic Med Sci. 2017;20:368–379.Search in Google Scholar

Received: 2017-12-01
Accepted: 2018-01-12
Published Online: 2018-02-17

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