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Opioid-Induced Androgen Deficiency (OPIAD): Diagnosis, Management, and Literature Review

  • Men’s Health (A Dabaja, Section Editor)
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Abstract

Opioid-induced androgen deficiency (OPIAD) was initially recognized as a possible consequence of opioid use roughly four decades ago. Long-acting opioid use carries risks of addiction, tolerance, and systemic side effects including hypogonadotropic hypogonadism with consequent testosterone depletion leading to multiple central and peripheral effects. Hypogonadism is induced through direct inhibitory action of opioids on receptors within the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes as well as testosterone production within the testes. Few studies have systematically investigated hormonal changes induced by long-term opioid administration or the effects of testosterone replacement therapy (TRT) in patients with OPIAD. Clomiphene citrate, a selective estrogen receptor modulator (SERM), is a testosterone enhancement treatment which upregulates endogenous hypothalamic function. This review will focus on the pathophysiology, diagnosis, and management of OPIAD, including summary of literature evaluating OPIAD treatment with TRT, and areas of future investigation.

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References

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  1. Daniell HW. Hypogonadism in men consuming sustained-action oral opioids. J Pain. 2002;3(5):377–84.

    Article  PubMed  Google Scholar 

  2. Cicero TJ. Opiate and opioid modulation of reproductive endocrinology in the male and female: development and pregestational aspects. NIDA Res Monogr. 1984;55:14–23.

    CAS  PubMed  Google Scholar 

  3. Rosenblum A, Marsch LA, Joseph H, Portenoy RK. Opioids and the treatment of chronic pain: controversies, current status, and future directions. Exp Clin Psychopharmacol. 2008;16(5):405–16. doi:10.1037/a0013628.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Schug SA, Zech D, Grond S. Adverse effects of systemic opioid analgesics. Drug Saf. 1992;7(3):200–13.

    Article  CAS  PubMed  Google Scholar 

  5. Haddox J, Joransen DE, Angarola RT. The use of opioids for the treatment of chronic pain. A consensus statement from the American Academy of Pain Medicine and the American Pain Society. Clin J Pain. 1997;13(1):6–8.

    Article  Google Scholar 

  6. Azizi F, Vagenakis AG, Longcope C, Ingbar SH, Braverman LE. Decreased serum testosterone concentration in male heroin and methadone addicts. Steroids. 1973;22(4):467–72.

    Article  CAS  PubMed  Google Scholar 

  7. Katz N, Mazer NA. The impact of opioids on the endocrine system. Clin J Pain. 2009;25(2):170–5. doi:10.1097/AJP.0b013e3181850df6.

    Article  PubMed  Google Scholar 

  8. Aloisi AM, Pari G, Ceccarelli I, Vecchi I, Ietta F, Lodi L, et al. Gender-related effects of chronic non-malignant pain and opioid therapy on plasma levels of macrophage migration inhibitory factor (MIF). Pain. 2005;115(1-2):142–51. doi:10.1016/j.pain.2005.02.019.

    Article  CAS  PubMed  Google Scholar 

  9. 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(6):2215–22. doi:10.1210/jcem.85.6.6615.

    Article  CAS  PubMed  Google Scholar 

  10. Rajagopal A, Vassilopoulou-Sellin R, Palmer JL, Kaur G, Bruera E. Symptomatic hypogonadism in male survivors of cancer with chronic exposure to opioids. Cancer. 2004;100(4):851–8. doi:10.1002/cncr.20028.

    Article  CAS  PubMed  Google Scholar 

  11. Birthi P, Nagar VR, Nickerson R, Sloan PA. Hypogonadism associated with long-term opioid therapy: a systematic review. J Opioid Manage. 2015;11(3):255–78. doi:10.5055/jom.2015.0274.

    Article  Google Scholar 

  12. Woody G, McLellan AT, O’Brien C, Persky H, Stevens G, Arndt I, et al. Hormone secretion in methadone-dependent and abstinent patients. NIDA Res Monogr. 1988;81:216–23.

    CAS  PubMed  Google Scholar 

  13. Ceccarelli I, De Padova AM, Fiorenzani P, Massafra C, Aloisi AM. Single opioid administration modifies gonadal steroids in both the CNS and plasma of male rats. Neuroscience. 2006;140(3):929–37. doi:10.1016/j.neuroscience.2006.02.044.

    Article  CAS  PubMed  Google Scholar 

  14. McDonald JP, Torrey AJ, Mehta MP, Delima LG. Beyond respiratory depression and constipation: adverse effects of opioids. J Miss State Med Assoc. 2015;56(7):193–5.

    PubMed  Google Scholar 

  15. Gudin JA, Laitman A, Nalamachu S. Opioid related endocrinopathy. Pain Med. 2015;16 Suppl 1:S9–15. doi:10.1111/pme.12926.

    Article  PubMed  Google Scholar 

  16. Lundh D, Hedelin H, Jonsson K, Gifford M, Larsson D. Assessing chronic pelvic pain syndrome patients: blood plasma factors and cortisol saliva. Scand J Urol. 2013;47(6):521–8. doi:10.3109/21681805.2013.769460.

    Article  CAS  PubMed  Google Scholar 

  17. Forman LJ, Tingle V, Estilow S, Cater J. The response to analgesia testing is affected by gonadal steroids in the rat. Life Sci. 1989;45(5):447–54.

    Article  CAS  PubMed  Google Scholar 

  18. Carullo V, Fitz-James I, Delphin E. Opioid-induced hyperalgesia: a diagnostic dilemma. J Pain Palliat Care Pharmacother. 2015;29(4):378–84. doi:10.3109/15360288.2015.1082006.

    Article  PubMed  Google Scholar 

  19. Eichenbaum G, Gohler K, Etropolski M, Steigerwald I, Pergolizzi J, Kim M, et al. Does tapentadol affect sex hormone concentrations differently from morphine and oxycodone? An initial assessment and possible implications for opioid-induced androgen deficiency. J Opioid Manage. 2015;11(3):211–27. doi:10.5055/jom.2015.0270.

    Article  Google Scholar 

  20. Bawor M, Bami H, Dennis BB, Plater C, Worster A, Varenbut M, et al. Testosterone suppression in opioid users: a systematic review and meta-analysis. Drug Alcohol Depend. 2015;149:1–9. doi:10.1016/j.drugalcdep.2015.01.038.

    Article  CAS  PubMed  Google Scholar 

  21. Rubinstein AL, Carpenter DM, Minkoff JR. Hypogonadism in men with chronic pain linked to the use of long-acting rather than short-acting opioids. Clin J Pain. 2013;29(10):840–5. doi:10.1097/AJP.0b013e31827c7b5d.

    Article  PubMed  Google Scholar 

  22. Rubinstein A, Carpenter DM. Elucidating risk factors for androgen deficiency associated with daily opioid use. Am J Med. 2014;127(12):1195–201. doi:10.1016/j.amjmed.2014.07.015.

    Article  CAS  PubMed  Google Scholar 

  23. McCarthy M. Opioids should be last resort to treat chronic pain, says draft CDC guideline. BMJ. 2015;351:h6905. doi:10.1136/bmj.h6905.

    Article  PubMed  Google Scholar 

  24. Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain—United States, 2016. MMWR Recomm Rep. 2016;65(1):1–49. doi:10.15585/mmwr.rr6501e1.

    Article  PubMed  Google Scholar 

  25. Elliott JA, Horton E, Fibuch EE. The endocrine effects of long-term oral opioid therapy: a case report and review of the literature. J Opioid Manag. 2011;7(2):145–54.

    PubMed  Google Scholar 

  26. Morley JE. The endocrinology of the opiates and opioid peptides. Metab Clin Exp. 1981;30(2):195–209.

    Article  CAS  PubMed  Google Scholar 

  27. Paice JA, Penn RD, Ryan WG. Altered sexual function and decreased testosterone in patients receiving intraspinal opioids. J Pain Symptom Manag. 1994;9(2):126–31.

    Article  CAS  Google Scholar 

  28. Cicero TJ, Schainker BA, Meyer ER. Endogenous opioids participate in the regulation of the hypothalamus-pituitary-luteinizing hormone axis and testosterone’s negative feedback control of luteinizing hormone. Endocrinology. 1979;104(5):1286–91. doi:10.1210/endo-104-5-1286.

    Article  CAS  PubMed  Google Scholar 

  29. Giri M, Kaufman JM. Opioidergic modulation of in vitro pulsatile gonadotropin-releasing hormone release from the isolated medial basal hypothalamus of the male guinea pig. Endocrinology. 1994;135(5):2137–43. doi:10.1210/endo.135.5.7956937.

    CAS  PubMed  Google Scholar 

  30. Graves GR, Kennedy TG, Weick RF, Casper RF. The effect of nalmefene on pulsatile secretion of luteinizing hormone and prolactin in men. Hum Reprod. 1993;8(10):1598–603.

    CAS  PubMed  Google Scholar 

  31. Veldhuis JD, Rogol AD, Samojlik E, Ertel NH. Role of endogenous opiates in the expression of negative feedback actions of androgen and estrogen on pulsatile properties of luteinizing hormone secretion in man. J Clin Invest. 1984;74(1):47–55. doi:10.1172/jci111417.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Pende A, Musso NR, Montaldi ML, Pastorino G, Arzese M, Devilla L. Evaluation of the effects induced by four opiate drugs, with different affinities to opioid receptor subtypes, on anterior pituitary LH, TSH, PRL and GH secretion and on cortisol secretion in normal men. Biomed Pharmacother. 1986;40(5):178–82.

    CAS  PubMed  Google Scholar 

  33. Andersson KE, Wagner G. Physiology of penile erection. Physiol Rev. 1995;75(1):191–236.

    CAS  PubMed  Google Scholar 

  34. Melis MR, Succu S, Spano MS, Argiolas A. Morphine injected into the paraventricular nucleus of the hypothalamus prevents noncontact penile erections and impairs copulation: involvement of nitric oxide. Eur J Neurosci. 1999;11(6):1857–64.

    Article  CAS  PubMed  Google Scholar 

  35. Melis MR, Succu S, Iannucci U, Argiolas A. Prevention by morphine of apomorphine- and oxytocin-induced penile erection and yawning: involvement of nitric oxide. Naunyn Schmiedeberg’s Arch Pharmacol. 1997;355(5):595–600.

    Article  CAS  Google Scholar 

  36. Daniell HW. DHEAS deficiency during consumption of sustained-action prescribed opioids: evidence for opioid-induced inhibition of adrenal androgen production. J Pain. 2006;7(12):901–7. doi:10.1016/j.jpain.2006.04.011.

    Article  CAS  PubMed  Google Scholar 

  37. Brennan MJ. The effect of opioid therapy on endocrine function. Am J Med. 2013;126(3 Suppl 1):S12–8. doi:10.1016/j.amjmed.2012.12.001.

    Article  CAS  PubMed  Google Scholar 

  38. Allolio B, Schulte HM, Deuss U, Kallabis D, Hamel E, Winkelman W. Effect of oral morphine and naloxone on pituitary-adrenal response in man induced by human corticotropin-releasing hormone. Acta Endocrinol. 1987;114(4):509–14.

    CAS  PubMed  Google Scholar 

  39. Delitala G, Grossman A, Besser GM. The participation of hypothalamic dopamine in morphine-induced prolactin release in man. Clin Endocrinol. 1983;19(4):437–44.

    Article  CAS  Google Scholar 

  40. Devilla L, Pende A, Morgano A, Giusti M, Musso NR, Lotti G. Morphine-induced TSH release in normal and hypothyroid subjects. Neuroendocrinology. 1985;40(4):303–8.

    Article  CAS  PubMed  Google Scholar 

  41. Rittmaster RS, Cutler Jr GB, Sobel DO, Goldstein DS, Koppelman MC, Loriaux DL, et al. Morphine inhibits the pituitary-adrenal response to ovine corticotropin-releasing hormone in normal subjects. J Clin Endocrinol Metab. 1985;60(5):891–5. doi:10.1210/jcem-60-5-891.

    Article  CAS  PubMed  Google Scholar 

  42. 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(3):200–10. doi:10.1016/j.jpain.2005.10.009.

    Article  CAS  PubMed  Google Scholar 

  43. Adams ML, Sewing B, Forman JB, Meyer ER, Cicero TJ. Opioid-induced suppression of rat testicular function. J Pharmacol Exp Ther. 1993;266(1):323–8.

    CAS  PubMed  Google Scholar 

  44. Kalra PS, Sahu A, Kalra SP. Opiate-induced hypersensitivity to testosterone feedback: pituitary involvement. Endocrinology. 1988;122(3):997–1003. doi:10.1210/endo-122-3-997.

    Article  CAS  PubMed  Google Scholar 

  45. Blank MS, Fabbri A, Catt KJ, Dufau ML. Inhibition of luteinizing hormone release by morphine and endogenous opiates in cultured pituitary cells. Endocrinology. 1986;118(5):2097–101. doi:10.1210/endo-118-5-2097.

    Article  CAS  PubMed  Google Scholar 

  46. Jordan D, Tafani JA, Ries C, Zajac JM, Simonnet G, Martin D, et al. Evidence for multiple opioid receptors in the human posterior pituitary. J Neuroendocrinol. 1996;8(11):883–7.

    Article  CAS  PubMed  Google Scholar 

  47. Agirregoitia E, Valdivia A, Carracedo A, Casis L, Gil J, Subiran N, et al. Expression and localization of delta-, kappa-, and mu-opioid receptors in human spermatozoa and implications for sperm motility. J Clin Endocrinol Metab. 2006;91(12):4969–75. doi:10.1210/jc.2006-0599.

    Article  CAS  PubMed  Google Scholar 

  48. Kew D, Muffly KE, Kilpatrick DL. Proenkephalin products are stored in the sperm acrosome and may function in fertilization. Proc Natl Acad Sci U S A. 1990;87(23):9143–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Davidson A, Vermesh M, Paulson RJ, Graczykowski JW, Lobo RA. Presence of immunoreactive beta-endorphin and calcitonin in human seminal plasma, and their relation to sperm physiology. Fertil Steril. 1989;51(5):878–80.

    Article  CAS  PubMed  Google Scholar 

  50. Agirregoitia E, Subiran N, Valdivia A, Gil J, Zubero J, Irazusta J. Regulation of human sperm motility by opioid receptors. Andrologia. 2012;44 Suppl 1:578–85. doi:10.1111/j.1439-0272.2011.01230.x.

    Article  PubMed  Google Scholar 

  51. Subiran N, Candenas L, Pinto FM, Cejudo-Roman A, Agirregoitia E, Irazusta J. Autocrine regulation of human sperm motility by the met-enkephalin opioid peptide. Fertil Steril. 2012;98(3):617–25.e3. doi:10.1016/j.fertnstert.2012.05.036.

    Article  CAS  PubMed  Google Scholar 

  52. Ragni G, De Lauretis L, Bestetti O, Sghedoni D, Gambaro V. Gonadal function in male heroin and methadone addicts. Int J Androl. 1988;11(2):93–100.

    Article  CAS  PubMed  Google Scholar 

  53. Safarinejad MR, Asgari SA, Farshi A, Ghaedi G, Kolahi AA, Iravani S, et al. The effects of opiate consumption on serum reproductive hormone levels, sperm parameters, seminal plasma antioxidant capacity and sperm DNA integrity. Reprod Toxicol. 2013;36:18–23. doi:10.1016/j.reprotox.2012.11.010.

    Article  CAS  PubMed  Google Scholar 

  54. Vanderschueren D, Vandenput L, Boonen S, Lindberg MK, Bouillon R, Ohlsson C. Androgens and bone. Endocr Rev. 2004;25(3):389–425. doi:10.1210/er.2003-0003.

    Article  CAS  PubMed  Google Scholar 

  55. Perez-Castrillon JL, Olmos JM, Gomez JJ, Barrallo A, Riancho JA, Perera L, et al. Expression of opioid receptors in osteoblast-like MG-63 cells, and effects of different opioid agonists on alkaline phosphatase and osteocalcin secretion by these cells. Neuroendocrinology. 2000;72(3):187–94.

    Article  CAS  PubMed  Google Scholar 

  56. Irwig MS. Bone health in hypogonadal men. Curr Opin Urol. 2014;24(6):608–13. doi:10.1097/mou.0000000000000104.

    Article  PubMed  Google Scholar 

  57. Hannemann A, Breer S, Wallaschofski H, Nauck M, Baumeister SE, Barvencik F, et al. Osteocalcin is associated with testosterone in the general population and selected patients with bone disorders. Andrology. 2013;1(3):469–74. doi:10.1111/j.2047-2927.2012.00044.x.

    Article  CAS  PubMed  Google Scholar 

  58. Gotthardt F, Huber C, Thierfelder C, Grize L, Kraenzlin M, Scheidegger C, et al. Bone mineral density and its determinants in men with opioid dependence. J Bone Miner Metab. 2016. doi:10.1007/s00774-015-0732-9.

    PubMed  Google Scholar 

  59. Finch PM, Price LM, Pullan PT, Drummond PD. Effects of testosterone treatment on bone mineral density in hypogonadal men receiving intrathecal opioids. Pain Pract. 2015;15(4):308–13. doi:10.1111/papr.12190. This was essentially a cross-sectional study that further informed the treatment response to TRT in those taking opioids, in this case intrathecal opioids. Of note, this study also examined BMD through DEXA, a critical outcome in hypogonadal patients.

    Article  PubMed  Google Scholar 

  60. Basaria S, Travison TG, Alford D, Knapp PE, Teeter K, Cahalan C, et al. Effects of testosterone replacement in men with opioid-induced androgen deficiency: a randomized controlled trial. Pain. 2015;156(2):280–8. doi:10.1097/01.j.pain.0000460308.86819.aa. This was the first double-blinded, placebo-controlled randomized control trial evaluating the effectiveness of TRT in patients with OPIAD. The authors also evaluated QoL measures concordantly with T measurements and should be commended for utilization of the International Index of Erectile Function as a validated study tool.

    Article  CAS  PubMed  Google Scholar 

  61. Huang G, Travison T, Maggio M, Edwards RR, Basaria S. Effects of testosterone replacement on metabolic and inflammatory markers in men with opioid-induced androgen deficiency. Clin Endocrinol. 2016. doi:10.1111/cen.13049. This was a second double-blinded, placebo-controlled randomized control trial with patients from the TAP trial included. Safety outcomes related to TRT were examined and are of vital importance as the management approach for OPIAD is further elucidated.

    Google Scholar 

  62. Aloisi AM, Ceccarelli I, Carlucci M, Suman A, Sindaco G, Mameli S, et al. Hormone replacement therapy in morphine-induced hypogonadic male chronic pain patients. Reprod Biol Endocrinol. 2011;9:26. doi:10.1186/1477-7827-9-26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. 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. 2012;13(5):688–98. doi:10.1111/j.1526-4637.2012.01368.x. This was the third single-arm study evaluating the effectiveness and utility of TRT in patients in with OPIAD.

    Article  PubMed  Google Scholar 

  64. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95(6):2536–59. doi:10.1210/jc.2009-2354.

    Article  CAS  PubMed  Google Scholar 

  65. Montorsi F, Adaikan G, Becher E, Giuliano F, Khoury S, Lue TF, et al. Summary of the recommendations on sexual dysfunctions in men. J Sex Med. 2010;7(11):3572–88. doi:10.1111/j.1743-6109.2010.02062.x.

    Article  PubMed  Google Scholar 

  66. Healy S, Hartman A, Gustin J. Opioid-induced androgen deficiency #284. J Palliat Med. 2014;17(11):1278–9. doi:10.1089/jpm.2014.9398.

    Article  PubMed  Google Scholar 

  67. Morley JE, Charlton E, Patrick P, Kaiser FE, Cadeau P, McCready D, et al. Validation of a screening questionnaire for androgen deficiency in aging males. Metab Clin Exp. 2000;49(9):1239–42. doi:10.1053/meta.2000.8625.

    Article  CAS  PubMed  Google Scholar 

  68. Heufelder AE, Saad F, Bunck MC, Gooren L. Fifty-two-week treatment with diet and exercise plus transdermal testosterone reverses the metabolic syndrome and improves glycemic control in men with newly diagnosed type 2 diabetes and subnormal plasma testosterone. J Androl. 2009;30(6):726–33. doi:10.2164/jandrol.108.007005.

    Article  CAS  PubMed  Google Scholar 

  69. Finkle WD, Greenland S, Ridgeway GK, Adams JL, Frasco MA, Cook MB, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One. 2014;9(1):e85805. doi:10.1371/journal.pone.0085805.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Seftel AD, Kathrins M, Niederberger C. Critical update of the 2010 Endocrine Society Clinical Practice Guidelines for male hypogonadism: a systematic analysis. Mayo Clin Proc. 2015;90(8):1104–15. doi:10.1016/j.mayocp.2015.06.002.

    Article  PubMed  Google Scholar 

  71. Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, et al. Effects of testosterone treatment in older men. N Engl J Med. 2016;374(7):611–24. doi:10.1056/NEJMoa1506119.

    Article  CAS  PubMed  Google Scholar 

  72. Morgentaler A, Traish AM. Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. Eur Urol. 2009;55(2):310–20. doi:10.1016/j.eururo.2008.09.024.

    Article  PubMed  Google Scholar 

  73. Rhoden EL, Morgentaler A. Risks of testosterone-replacement therapy and recommendations for monitoring. N Engl J Med. 2004;350(5):482–92. doi:10.1056/NEJMra022251.

    Article  CAS  PubMed  Google Scholar 

  74. Goodman N, Guay A, Dandona P, Dhindsa S, Faiman C, Cunningham GR. American Association of Clinical Endocrinologists and American College of Endocrinology position statement on the association of testosterone and cardiovascular risk. Endocr Pract. 2015;21(9):1066–73. doi:10.4158/ep14434.ps.

    Article  PubMed  Google Scholar 

  75. Murphy EN, Miranda R. Doubts about treating hypogonadism due to long-term opioid use with testosterone therapy: a teachable moment. JAMA Intern Med. 2014;174(12):1892–3. doi:10.1001/jamainternmed.2014.5299.

    Article  PubMed  Google Scholar 

  76. Moradi M, Mahmoodi M, Raoofi A, Ghanbari A. Chorionic morphine, naltrexone and pentoxifylline effect on hypophyso-gonadal hormones of male rats. Bratisl Lek Listy. 2015;116(4):276–9.

    CAS  PubMed  Google Scholar 

  77. Wosnitzer MS, Schlegel PN. Clomiphene citrate for the treatment of low testosterone associated with chronic opioid pain medication administration. 2013.

  78. Practice Committee of the American Society for Reproductive Medicine. Use of clomiphene citrate in women. Fertil Steril. 2006;86(5 Suppl 1):S187–93. doi:10.1016/j.fertnstert.2006.08.023.

    Google Scholar 

  79. Shabsigh A, Kang Y, Shabsign R, Gonzalez M, Liberson G, Fisch H, et al. Clomiphene citrate effects on testosterone/estrogen ratio in male hypogonadism. J Sex Med. 2005;2(5):716–21. doi:10.1111/j.1743-6109.2005.00075.x.

    Article  CAS  PubMed  Google Scholar 

  80. Tan RS, Vasudevan D. Use of clomiphene citrate to reverse premature andropause secondary to steroid abuse. Fertil Steril. 2003;79(1):203–5.

    Article  PubMed  Google Scholar 

  81. Guay AT, Bansal S, Heatley GJ. Effect of raising endogenous testosterone levels in impotent men with secondary hypogonadism: double blind placebo-controlled trial with clomiphene citrate. J Clin Endocrinol Metab. 1995;80(12):3546–52. doi:10.1210/jcem.80.12.8530597.

    CAS  PubMed  Google Scholar 

  82. Moskovic DJ, Katz DJ, Akhavan A, Park K, Mulhall JP. Clomiphene citrate is safe and effective for long-term management of hypogonadism. BJU Int. 2012;110(10):1524–8. doi:10.1111/j.1464-410X.2012.10968.x.

    Article  CAS  PubMed  Google Scholar 

  83. Katz DJ, Nabulsi O, Tal R, Mulhall JP. Outcomes of clomiphene citrate treatment in young hypogonadal men. BJU Int. 2012;110(4):573–8. doi:10.1111/j.1464-410X.2011.10702.x.

    Article  CAS  PubMed  Google Scholar 

  84. Reifsnyder JE, Ramasamy R, Husseini J, Schlegel PN. Role of optimizing testosterone before microdissection testicular sperm extraction in men with nonobstructive azoospermia. J Urol. 2012;188(2):532–6. doi:10.1016/j.juro.2012.04.002.

    Article  CAS  PubMed  Google Scholar 

  85. Taylor F, Levine L. Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: efficacy and treatment cost. J Sex Med. 2010;7(1 Pt 1):269–76. doi:10.1111/j.1743-6109.2009.01454.x.

    Article  CAS  PubMed  Google Scholar 

  86. Hussein A, Ozgok Y, Ross L, Niederberger C. Clomiphene administration for cases of nonobstructive azoospermia: a multicenter study. J Androl. 2005;26(6):787–91. doi:10.2164/jandrol.04180. discussion 92-3.

    Article  CAS  PubMed  Google Scholar 

  87. Hussein A, Ozgok Y, Ross L, Rao P, Niederberger C. Optimization of spermatogenesis-regulating hormones in patients with non-obstructive azoospermia and its impact on sperm retrieval: a multicentre study. BJU Int. 2013;111(3 Pt B):E110–4. doi:10.1111/j.1464-410X.2012.11485.x.

    Article  CAS  PubMed  Google Scholar 

  88. Ramasamy R, Ricci JA, Palermo GD, Gosden LV, Rosenwaks Z, Schlegel PN. Successful fertility treatment for Klinefelter’s syndrome. J Urol. 2009;182(3):1108–13. doi:10.1016/j.juro.2009.05.019.

    Article  CAS  PubMed  Google Scholar 

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Timothy K. O’Rourke, Jr. and Matthew S. Wosnitzer each declare no potential conflicts of interest.

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O’Rourke, T.K., Wosnitzer, M.S. Opioid-Induced Androgen Deficiency (OPIAD): Diagnosis, Management, and Literature Review. Curr Urol Rep 17, 76 (2016). https://doi.org/10.1007/s11934-016-0634-y

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