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Hormone Molecular Biology and Clinical Investigation

Editor-in-Chief: Chetrite, Gérard S.

Editorial Board: Alexis, Michael N. / Baniahmad, Aria / Beato, Miguel / Bouillon, Roger / Brodie, Angela / Carruba, Giuseppe / Chen, Shiuan / Cidlowski, John A. / Clarke, Robert / Coelingh Bennink, Herjan J.T. / Darbre, Philippa D. / Drouin, Jacques / Dufau, Maria L. / Edwards, Dean P. / Falany, Charles N. / Fernandez-Perez, Leandro / Ferroud, Clotilde / Feve, Bruno / Flores-Morales, Amilcar / Foster, Michelle T. / Garcia-Segura, Luis M. / Gastaldelli, Amalia / Gee, Julia M.W. / Genazzani, Andrea R. / Greene, Geoffrey L. / Groner, Bernd / Hampl, Richard / Hilakivi-Clarke, Leena / Hubalek, Michael / Iwase, Hirotaka / Jordan, V. Craig / Klocker, Helmut / Kloet, Ronald / Labrie, Fernand / Mendelson, Carole R. / Mück, Alfred O. / Nicola, Alejandro F. / O'Malley, Bert W. / Raynaud, Jean-Pierre / Ruan, Xiangyan / Russo, Jose / Saad, Farid / Sanchez, Edwin R. / Schally, Andrew V. / Schillaci, Roxana / Schindler, Adolf E. / Söderqvist, Gunnar / Speirs, Valerie / Stanczyk, Frank Z. / Starka, Luboslav / Sutter, Thomas R. / Tresguerres, Jesús A. / Wahli, Walter / Wildt, Ludwig / Yang, Kaiping / Yu, Qi

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Impact of opioid therapy on gonadal hormones: focus on buprenorphine

Anjali Varma
  • Corresponding author
  • Mental Health Clinic, Lead Psychiatrist Buprenorphine Clinic, Veterans Affairs Medical Centre, 1970 Roanoke Blvd., Salem, VA, USA, Phone: +5409822463, ext 3555, Fax: +540-855-3452
  • Department of Psychiatry and Behavioral Medicine, Virginia Tech Carilion School of Medicine, Roanoke, VA, USA
  • Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Roanoke, VA, USA
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Mamta Sapra
  • Department of Psychiatry and Behavioral Medicine, Virginia Tech Carilion School of Medicine, Roanoke, VA, USA
  • Memory Assessment Clinic, Chair, IRB, Veterans Affairs Medical Centre, 1970 Roanoke Blvd., Salem, VA, USA
  • Other articles by this author:
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/ Ali Iranmanesh
  • Veterans Affairs Medical Centre, Salem, VA, USA
  • Virginia Tech Carilion School of Medicine, Roanoke, VA, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2018-02-17 | DOI: https://doi.org/10.1515/hmbci-2017-0080

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.

Keywords: buprenorphine; endocrinopathy; HPG; hypogonadism; LH; opioids; testosterone

References

  • [1]

    NSDUH Report. America’s behavioral health-changes and challenges. 2016. www.SAMHSA.GOV/DATA.

  • [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.CrossrefPubMedGoogle Scholar

  • [3]

    Pasternak GW. The opiate receptors 2010. 2nd ed. New York, NY, USA: Humana Press; 2010. p. 23–48.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.PubMedWeb of ScienceCrossrefGoogle Scholar

  • [5]

    Ling W, Wesson DR. Clinical efficacy of buprenorphine: comparisons to methadone and placebo. Drug Alcohol Depend. 2003;70:S49–57.CrossrefPubMedGoogle Scholar

  • [6]

    Dunlap B, Cifu AS. Clinical management of opioid use disorder. J Am Med Assoc. 2016;316:338–9.CrossrefGoogle 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.Web of SciencePubMedCrossrefGoogle 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.PubMedCrossrefGoogle 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.CrossrefPubMedGoogle Scholar

  • [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.CrossrefPubMedGoogle Scholar

  • [11]

    Daniell HW. Opioid endocrinopathy in women consuming prescribed sustained-action opioids for control of nonmalignant pain. J Pain. 2008;9:28–36.CrossrefPubMedWeb of ScienceGoogle Scholar

  • [12]

    Daniell HW. Hypogonadism in men consuming sustained-action oral opioids. J Pain. 2002;3:377–84.CrossrefPubMedGoogle Scholar

  • [13]

    Katz N, Mazer NA. The impact of opioids on the endocrine system. Clin J Pain. 2009;25:170–5.Web of SciencePubMedCrossrefGoogle Scholar

  • [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.PubMedGoogle 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.CrossrefPubMedGoogle Scholar

  • [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.CrossrefPubMedGoogle Scholar

  • [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.PubMedCrossrefGoogle Scholar

  • [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.CrossrefGoogle 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.CrossrefWeb of SciencePubMedGoogle Scholar

  • [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.CrossrefPubMedWeb of ScienceGoogle Scholar

  • [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).CrossrefWeb of ScienceGoogle 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.Web of ScienceCrossrefPubMedGoogle Scholar

  • [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.CrossrefPubMedWeb of ScienceGoogle Scholar

  • [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.CrossrefPubMedWeb of ScienceGoogle Scholar

  • [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.PubMedCrossrefGoogle Scholar

  • [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.CrossrefWeb of SciencePubMedGoogle 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.PubMedGoogle 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.CrossrefPubMedGoogle Scholar

  • [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.Web of ScienceGoogle Scholar

  • [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.PubMedGoogle Scholar

  • [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.CrossrefPubMedWeb of ScienceGoogle Scholar

  • [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.CrossrefPubMedGoogle Scholar

  • [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.PubMedCrossrefGoogle Scholar

  • [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.CrossrefPubMedGoogle 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.Web of ScienceGoogle Scholar

About the article

Received: 2017-12-01

Accepted: 2018-01-12

Published Online: 2018-02-17


Author Statement

Research funding: Authors state no funding involved.

Conflict of interest: Authors state no conflict of interest.

Informed consent: Informed consent is not applicable.

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


Citation Information: Hormone Molecular Biology and Clinical Investigation, 20170080, ISSN (Online) 1868-1891, DOI: https://doi.org/10.1515/hmbci-2017-0080.

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