Endocrine Effects of Chronic Opioid Therapy: Implications for Clinical Management

• Colamenco C , CorenJS. Opioid-induced endocrinopathy. J. Am. Osteopath. Assoc.109(1) , 20–25 (2009).
   PubMedGoogle Scholar
• Katz N , MazerNA. The impact of opioids on the endocrine system. Clin. J. Pain25(2) , 170–175 (2009).
   PubMed Web of Science ®Google Scholar
• Aloisi AM , BuonocoreM, MerloL et al. Chronic pain therapy and hypothalamic–pituitary–adrenal axis impairment. Psychoneuroendocrinology 36 , 1032–1039 (2011).
   PubMed Web of Science ®Google Scholar
• Aloisi AM , CeccarelliI, CarlucciM et al. Hormone replacement therapy in morphine-induced hypogonadic male chronic pain patients. Reprod. Biol. Endocrinol. 9 , 26 (2011).
   PubMed Web of Science ®Google Scholar
• Finch PM , RobertsLJ, PriceLS, HadlowNC, PullanPT. Hypogonadism in patients treated with intrathecal morphine. Clin. J. Pain16(3) , 251–254 (2000).
   PubMed Web of Science ®Google Scholar
• Paice JA , PennRD, RyanWG. Altered sexual function and decreased testosterone in patients receiving intraspinal opioids. J. Pain Symptom Manage.9(2) , 126–131 (1994).
   PubMed Web of Science ®Google Scholar
• Abs R , VerhelstJ, MaeyaertJ et al. Endocrine consequences of long-term intrathecal administration of opioids. J. Clin. Endocrinol. Metab. 85(6) , 2215–2222 (2000).
   PubMed Web of Science ®Google Scholar
• Roberts LJ , FinchPM, GouckeCR, PriceLM. Outcome of intrathecal opioids in chronic non-cancer pain. Eur. J. Pain5 , 353–361 (2001).
   PubMed Web of Science ®Google Scholar
• Bolelli G , LafiscaS, FlamigniC et al. Heroin addiction: relationship between the plasma levels of testosterone, dihydrotestosterone, androstenedione, LH, FSH, and the plasma concentration of heroin. Toxicology 15 , 19–29 (1979).
   PubMed Web of Science ®Google Scholar
• Daniell HW . Narcotic-induced hypogonadism during therapy for heroin addiction. J. Addict. Dis.21(4) , 47–53 (2002).
   PubMed Web of Science ®Google Scholar
• Fraser LA , MorrisonD, Morley-FosterP et al. Oral opioids for chronic non-cancer pain: higher prevalence of hypogonadism in men than in women. Exp. Clin. Endocrinol. Diabetes 117 , 38–43 (2009).
   PubMed Web of Science ®Google Scholar
• Rajogopal A , Vassilopoulou-SellinR, PalmerJL, KaurG, BrueraE. Symptomatic hypogonadism in male survivors of cancer with chronic exposure to opioids. Cancer100(4) , 851–858 (2004).
   PubMed Web of Science ®Google Scholar
• Daniell HW . Hypogonadism in men consuming sustained-action oral opioids. J. Pain3(5) , 377–384 (2002).
   PubMed Web of Science ®Google Scholar
• Daniell HW . Opioid endocrinopathy in women consuming prescribed sustained-action oral opioids for control of nonmalignant pain. J. Pain9(1) , 28–36 (2008).
   PubMed Web of Science ®Google Scholar
• Roberts LJ , FinchPM, PullanPT, BhagatCI, PriceLM. Sex hormone suppression by intrathecal opioids: a prospective study. Clin. J. Pain18 , 144–148 (2002).
   PubMed Web of Science ®Google Scholar
• Aloisi AM , AurilioC, BachioccoV et al. Endocrine consequences of opioid therapy. Psychoneuroendocrinology 34S , S162–S168 (2009).
   Google Scholar
• Blick G , KheraM, BhattacharyaRK, NguyenD, KushnerH, MinerMM. Testosterone replacement therapy outcomes among opioid users: the Testim registry in the United States (TRiUS). Pain Med.13 , 688–698 (2012).
   PubMed Web of Science ®Google Scholar
• Rhodin A , StridsbergM, GordhT. Opioid endocrinopathy: a clinical problem in patients with chronic pain and long-term oral opioid treatment. Clin. J. Pain26(5) , 374–380 (2010).
   PubMed Web of Science ®Google Scholar
• Merza Z . Chronic use of opioids and the endocrine system. Horm. Metab. Res.42 , 621–626 (2010).
   PubMed Web of Science ®Google Scholar
• Wong D , GrayD, SimmondsM, RashiqS, SobolevI, MorrishDW. Opioid analgesics suppress male gonadal function, but opioid use in men and women does not correlate with symptoms of sexual dysfunction. Pain Res. Manage.16(5) , 311–316 (2011).
   PubMed Web of Science ®Google Scholar
• Vuong C , Van Uum SHM, O‘Dell LE, Lufty K, Friedman TC. The effects of opioids and opioid analogs on animal and human endocrine systems. Endocr. Rev.31 , 98–132 (2010).
   PubMed Web of Science ®Google Scholar
• Elliott JA , HortonE, FibuchEE. The endocrine effects of long-term oral opioid therapy: a case report and review of the literature. J. Opioid Manage.7(2) , 145–154 (2011).
   PubMedGoogle Scholar
• Smith HS , ElliottJA. Opioid-induced androgen deficiency (OPIAD). Pain Physician15 , ES145–ES156 (2012).
   PubMed Web of Science ®Google Scholar
• De Maddalena C , BelliniM, BerraM, MeriggiolaMC, AloisiAM. Opioid-induced hypogonadism: why and how to treat it. Pain Physician15 , ES111–ES118 (2012).
   PubMed Web of Science ®Google Scholar
• Benyamin R , TrescotAM, DattaS et al. Opioid complications and side effects. Pain Physician 11 , S105–S120 (2008).
   PubMed Web of Science ®Google Scholar
• Daniell HW . DHEAS deficiency during consumption of sustained-action prescribed opioids: evidence for opioid-induced inhibition of adrenal androgen production. J. Pain7(12) , 901–907 (2006).
   PubMed Web of Science ®Google Scholar
• Strasser F , PalmerJL, SchoverLR et al. The impact of hypogonadism and autonomic dysfunction on fatigue, emotional function, and sexual desire in male patients with advanced cancer. Cancer 107 , 2949–2957 (2006).
   PubMed Web of Science ®Google Scholar
• Del Fabbro E , HuiD, NooruddinZI et al. Associations among hypogonadism, c-reactive protein, symptom burden, and survival in male cancer patients with cachexia: a preliminary report. J. Pain Symptom Manage. 39(6) , 1016–1024 (2010).
   PubMed Web of Science ®Google Scholar
• Dev R , HuiD, DalalS et al. Association between serum cortisol and testosterone levels, opioid therapy, and symptom distress in patients with advanced cancer. J. Pain Symptom Manage. 41(4) , 788–795 (2011).
   PubMed Web of Science ®Google Scholar
• Vanderschueren D , GaytantJ, BoonenS, VenkenK. Androgens and bone. Curr. Opin. Endocrinol. Diabetes Obes.15 , 250–254 (2008).
   PubMed Web of Science ®Google Scholar
• Corona G , RastrelliG, FortiG, MaggiM. Update in testosterone therapy for men. J. Sex. Med.8 , 639–654 (2011).
   PubMed Web of Science ®Google Scholar
• Amin S , ZhangY, FelsonDT et al. Estradiol, testosterone, and the risk for hip fractures in elderly men from the Framingham study. Am. J. Med. 119 , 426–433 (2006).
   PubMed Web of Science ®Google Scholar
• Fortin JD , BaileyGM, VilenskyJA. Does opioid use for pain management warrant routine bone mass density screening in men? Pain Physician11 , 539–541 (2008).
   PubMed Web of Science ®Google Scholar
• Reddy RG , AungT, KaravitakiN, WassJAH. Opioid induced hypogonadism. BMJ341 , c4462 (2010).
   PubMed Web of Science ®Google Scholar
• Zitzmann M . Testosterone and the brain. Aging Male9(4) , 195–199 (2006).
   PubMed Web of Science ®Google Scholar
• Amiaz R , SeidmanSN. Testosterone and depression in men. Curr. Opin. Endocrinol. Diabetes Obes.15 , 278–283 (2008).
   PubMed Web of Science ®Google Scholar
• Veras AB , NardiAE. The complex relationship between hypogonadism and major depression in a young male: letter to the editor (case report). Prog. Neuropsychopharmacol. Biol. Psychiatry34 , 421–422 (2010).
   PubMed Web of Science ®Google Scholar
• Almeida OP , YeapBB, HankeyGJ, JamrozikK, FlickerL. Low free testosterone concentration as a potentially treatable cause of depressive symptoms in older men. Arch. Gen. Psychiatry65(3) , 283–289 (2008).
   PubMed Web of Science ®Google Scholar
• Shores MM , KivlahanDR, SadakTI, LiEJ, MatsumotoAM. A randomized, double-blind, placebo-controlled study of testosterone treatment in hypogonadal older men with subthreshold depression (dysthymia or minor depression). J. Clin. Psychiatry70(7) , 1009–1016 (2009).
   PubMed Web of Science ®Google Scholar
• Traish AM , HassaniJ, GuayAT, ZitzmannM, HansenML. Adverse side effects of 5α-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients. J. Sex. Med.8 , 872–884 (2011).
   PubMed Web of Science ®Google Scholar
• Kennedy SE , KoeppeRA, YoungEA, ZubietaJK. Dysregulation of endogenous opioid emotion regulation circuitry in major depression in women. Arch. Gen. Psychiatry63 , 1199–1208 (2006).
   PubMed Web of Science ®Google Scholar
• Schmidt PH , BerlinKL, DanaceauMA et al. The effects of pharmacologically induced hypogonadism on mood in healthy men. Arch. Gen. Psychiatry 61 , 997–1004 (2004).
   PubMed Web of Science ®Google Scholar
• Jockenhövel F , MinnemannT, SchubertM et al. Timetable of effects of testosterone administration to hypogonadal men on variables of sex and mood. Aging Male 12(4) , 113–118 (2009).
   PubMed Web of Science ®Google Scholar
• Barrett-Connor E , von Mühlen DG, Kritz-Silverstein D. Bioavailable testosterone and depressed mood in older men: the Rancho Bernardo study. J. Clin. Endocrinol. Metab.84 , 573–577 (1999).
   PubMed Web of Science ®Google Scholar
• Tostain JL , BlancF. Testosterone deficiency: a common, unrecognized syndrome. Nat. Clin. Pract. Urol.5(7) , 388–396 (2008).
   PubMedGoogle Scholar
• Traish AM , MinerMM, MorgentalerA, ZitzmannM. Testosterone deficiency. Am. J. Med.124 , 578–587 (2011).
   PubMed Web of Science ®Google Scholar
• Zarrouf FA , ArtzS, GriffithJ, SirbuC, KommorM. Testosterone and depression: systematic review and meta-analysis. J. Psychiatr. Pract.15(4) , 289–305 (2009).
   PubMed Web of Science ®Google Scholar
• Seidman SN , OrrG, RavivG et al. Effects of testosterone replacement in middle-aged men with dysthymia: a randomized, placebo-controlled trial. J. Clin. Psychopharmacol. 29(3) , 216–221 (2009).
   PubMed Web of Science ®Google Scholar
• Perry PJ , YatesWR, WilliamsRD et al. Testosterone therapy in late-life major depression in males. J. Clin. Psychiatry 63(12) , 1096–1101 (2002).
   PubMed Web of Science ®Google Scholar
• Pope HG , CohaneGH, KanayamaG, SiegelAJ, HudsonJI. Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. Am. J. Psychiatry160(1) , 105–111 (2003).
   PubMed Web of Science ®Google Scholar
• Elliott JA , OpperSE, AgarwalS, FibuchEE. Non-analgesic effects of opioids: opioids and the endocrine system. Curr. Pharm. Des.18(37) , 6070–6078 (2012).
   PubMed Web of Science ®Google Scholar
• Dessin PH , ShiptonEA, StanwixAE, JoffeBI. Neuroendocrine deficiency-mediated development and persistence of pain in fibromyalgia: a promising paradigm? Pain86 , 213–215 (2000).
   PubMed Web of Science ®Google Scholar
• 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. Neuroscience140 , 929–937 (2006).
   PubMed Web of Science ®Google Scholar
• Craft RM , MogilJS, AloisiAM. Sex differences in pain and analgesia: the role of gonadal hormones. Eur. J. Pain8 , 397–411 (2004).
   PubMed Web of Science ®Google Scholar
• Craft RM . Modulation of pain by estrogens. Pain132 , S3–S12 (2007).
   PubMed Web of Science ®Google Scholar
• Wang C , NieschlagE, SwerdloffR et al. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. J. Androl. 30(1) , 1–9 (2009).
   PubMedGoogle Scholar
• Bachmann G , BancroftJ, BraunsteinG et al. Female androgen insufficiency: the Princeton consensus statement on definition, classification, and assessment. Fertil. Steril. 77(4) , 660–665 (2002).
   PubMed Web of Science ®Google Scholar
• Arlt W . Androgen therapy in women. Eur. J. Endocrinol.154 , 1–11 (2006).
   PubMed Web of Science ®Google Scholar
• AACE Menopause Guidelines Revision Task Force. Endocrinologist‘s guidelines for the diagnosis and treatment of menopause. Endocr. Pract.12(3) , 315–337 (2006).
   PubMedGoogle Scholar
• Bhasin S , CunninghamGR, HayesFJ et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 95(6) , 2536–2559 (2010).
   PubMed Web of Science ®Google Scholar
• Wierman ME , BassonR, DavisSR et al. Androgen therapy in women: an Endocrine Society guideline. J. Clin. Endocrinol. Metab. 91 , 3697–3710 (2006).
   PubMed Web of Science ®Google Scholar
• Bachmann G , OzaD. Female androgen insufficiency. Obstet. Gynecol. Clin. N. Am.33 , 589–598 (2006).
   PubMed Web of Science ®Google Scholar
• Tennant F , LichotaL. Testosterone replacement in chronic pain patients. Pract. Pain Manage.10(6) , 12–15 (2010).
   Google Scholar
• Tennant F . Testosterone replacement in female chronic pain patients. Pract. Pain Manage.9(9) , 25–27 (2009).
   Google Scholar
• Auernhammer CJ , VlotidesG. Anterior pituitary hormone replacement therapy: a clinical review. Pituitary10 , 1–15 (2007).
   PubMed Web of Science ®Google Scholar
• Miller KK . Androgen deficiency in women. J. Clin. Endocrinol. Metab.86(6) , 2395–2401 (2001).
   PubMed Web of Science ®Google Scholar
• Davis S . Androgen replacement in women. J. Clin. Endocrinol. Metab.84 , 1886–1891 (1999).
   PubMed Web of Science ®Google Scholar
• Mazer NA . Testosterone deficiency in women: etiologies, diagnosis, and emerging treatments. Int. J. Fertil.47(2) , 77–86 (2002).
   Google Scholar

▪ Websites

• Causes of secondary hypogonadism in males. In: UpToDate. Matsumoto AM, Kirkland JL, Martin KA (Eds). MA, USA (2012). www.uptodate.com/contents/causes-of-secondary-hypogonadism-in-males?source=search_result&search=secodary+hypogonadism+in+males&selectedTitle=4%7E150 (Accessed 26December2012)
   Google Scholar
• Merck Manual Professional. Male hypogonadism: male endocrinology. www.merck.com/mmpe/sec17/ch227/ch227b.html (Accessed 17December2012)
   Google Scholar
• Epidemiology and etiology of osteoporosis in men. In: UpToDate. Rosen CJ, Mulder JE (Eds). MA, USA (2012). www.uptodate.com/contents/epidemiology-and-etiology-of-osteoporosis-in-men?source=search_result&search=epidemiology+and+etiology+of+osteoporosi&selectedTitle=2%7E150 (Accessed 26December2012)
   Google Scholar
• Manolagas SC. Pathogenesis of osteoporosis. In: UpToDate. Rosen CJ, Mulder JE (Eds). MA, USA (2012). www.uptodate.com/contents/pathogenesis-of-osteoporosis?source=search_result&search=osteoporosis&selectedTitle=9%7E150 (Accessed 26December2012)
   Google Scholar
• Snyder PJ. Testosterone treatment of male hypogonadism. In: UpToDate. Matsumoto AM, Martin KA (Eds). MA, USA (2012). www.uptodate.com/contents/testosterone-treatment-of-male-hypogonadism?source=search_result&search=testosterone&selectedTitle=5%7E150 (Accessed 26December2012)
   Google Scholar
• Lexi-Comp Online: testosterone. www.lexi.com (Accessed 26December2012)
   Google Scholar