Effects of testosterone replacement in men with opioid-induced androgen deficiency: a randomized controlled trial
Open accessAbstract
Symptomatic androgen deficiency is common in patients taking opioid analgesics, as these drugs potently suppress the hypothalamic-pituitary-gonadal axis. However, the efficacy of testosterone replacement in this setting remains unclear. The objective of this trial was to evaluate the efficacy of testosterone replacement on pain perception and other androgen-dependent outcomes in men with opioid-induced androgen deficiency. We conducted a randomized, double-blind, parallel placebo-controlled trial at an outpatient academic research center. Participants were men aged 18 to 64 years on opioid analgesics for chronic noncancer pain, and total testosterone levels were <350 ng/dL. Participants were randomly assigned to 14 weeks of daily transdermal gel that contained 5 g of testosterone or placebo. Primary outcomes were changes in self-reported clinical pain and objectively assessed pain sensitivity. Sexual function, quality of life, and body composition were also assessed. The mean age was 49 years. The median total and free testosterone levels at baseline were 243 ng/dL and 47 pg/mL and 251 ng/dL and 43 pg/mL in the testosterone and placebo arm, respectively. Of the 84 randomized participants, 65 had follow-up data on efficacy outcomes. Compared with men assigned to the placebo arm, those assigned to testosterone replacement experienced greater improvements in pressure and mechanical hyperalgesia, sexual desire, and role limitation due to emotional problems. Testosterone administration was also associated with an improvement in body composition. There were no between-group differences in changes in self-reported pain. In conclusion, in men with opioid-induced androgen deficiency, testosterone administration improved pain sensitivity, sexual desire, body composition, and aspects of quality of life.
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Cites
(1992) · PubMed · Cited by 33,716 · see citing works
The MOS 36-ltem Short-Form Health Survey (SF-36): I. Conceptual Framework and Item Selection
Ware, J. E., & Sherbourne, C. D. (1992) · Medical Care · doi:10.1097/00005650-199206000-00002 · Cited by 30,033 · see citing works
Rosen, R. C., Riley, A., Wagner, G., Osterloh, I. H., Kirkpatrick, J., & Mishra, A. (1997) · Urology · doi:10.1016/s0090-4295(97)00238-0 · Cited by 5,849 · see citing works
A Critical Evaluation of Simple Methods for the Estimation of Free Testosterone in Serum
Vermeulen, A., Verdonck, L., & Kaufman, J. M. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.10.6079 · Cited by 3,824 · see citing works
Validation of the Brief Pain Inventory for chronic nonmalignant pain
Tan, G., Jensen, M. P., Thornby, J. I., & Shanti, B. F. (2004) · The Journal of Pain · doi:10.1016/j.jpain.2003.12.005 · Cited by 1,416 · cited 1× · see citing works
“The BPI is a validated measure of pain severity and pain interference for patients with chronic pain.(34) The QST was performed in the pain laboratory to assess sensitivity to calibrated mechanical and thermal (cold) noxious stimuli while the subjects sat comfortably in a reclining chair.”
Role of the Immune system in chronic pain
Marchand, F., Perretti, M., & McMahon, S. B. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1700 · Cited by 1,098 · see citing works
Katznelson, L., Finkelstein, J. S., Schoenfeld, D. A., Rosenthal, D. I., Anderson, E. J., & Klibanski, A. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.12.8954042 · Cited by 791 · cited 1× · see citing works
“Testosterone deficiency is associated with a decrease in lean mass and an increase in fat mass, a phenotype associated with reduced muscle strength and function.(6,24) Although effects of testosterone therapy on body composition are well established in other patient populations, it had not been studied in men with opi…”
BackgroundPrediction of chronic post-operative pain: Pre-operative DNIC testing identifies patients at risk
Yarnitsky, D., Crispel, Y., Eisenberg, E., Granovsky, Y., Ben-Nun, A., Sprecher, E., Best, L.-A., & Granot, M. (2008) · Pain · doi:10.1016/j.pain.2007.10.033 · Cited by 750 · see citing works
Malkin, C. J., Pugh, P. J., Jones, R. D., Kapoor, D., Channer, K. S., & Jones, T. H. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031069 · Cited by 731 · see citing works
Opioid-induced Hyperalgesia in Humans
Chu, L. F., Angst, M. S., & Clark, J. D. (2008) · Clinical Journal of Pain · doi:10.1097/ajp.0b013e31816b2f43 · Cited by 572 · see citing works
The effects of opioids and opioid analogs on animal and human endocrine systems
Vuong, C., Van Uum, S. H. M., O'Dell, L. E., Lutfy, K., & Friedman, T. C. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0009 · Cited by 564 · see citing works
Arendt‐Nielsen, L., & Yarnitsky, D. (2009) · Journal of Pain · doi:10.1016/j.jpain.2009.02.002 · Cited by 548 · see citing works
Assessment of mechanisms in localized and widespread musculoskeletal pain
Graven‐Nielsen, T., & Arendt‐Nielsen, L. (2010) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2010.107 · Cited by 547 · see citing works
Endocrine consequences of long-term intrathecal administration of opioids
Abs, R., Verhelst, J., Maeyaert, J., Van Buyten, J.-P., Opsomer, F., Adriaensen, H., Verlooy, J., Van Havenbergh, T., Smet, M., & Van Acker, K. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.6.6615 · Cited by 491 · see citing works
Hypogonadism in men consuming sustained-action oral opioids
Daniell, H. W. (2002) · The Journal of Pain · doi:10.1054/jpai.2002.126790 · Cited by 401 · see citing works
Sex-Based Differences in Pain Perception and Treatment
Paller, C. J., Campbell, C. M., Edwards, R. R., & Dobs, A. S. (2009) · Pain Medicine · doi:10.1111/j.1526-4637.2008.00558.x · Cited by 396 · see citing works
Self-citationBhasin, S., Pencina, M., Jasuja, G. K., Travison, T. G., Coviello, A., Orwoll, E., Wang, P. Y., Nielson, C., Wu, F., Tajar, A., et al. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-3012 · Cited by 355 · see citing works
Self-citationBasaria, S. (2014) · The Lancet · doi:10.1016/s0140-6736(13)61126-5 · Cited by 328 · see citing works
Self-citationPrevalence of pain in the Spanish population telephone survey in 5000 homes
Catalá, E., Reig, E., Artés, M. T., Aliaga, L., López, J. R. G., & Segú, J. L. (2002) · European Journal of Pain · doi:10.1053/eujp.2001.0310 · Cited by 284 · see citing works
Long-Term Opioid Therapy Reconsidered
Korff, M. V., Kolodny, A., Deyo, R. A., & Chou, R. (2011) · Annals of Internal Medicine · doi:10.7326/0003-4819-155-5-201109060-00011 · Cited by 261 · see citing works
Postcesarean Section Pain Prediction by Preoperative Experimental Pain Assessment
Granot, M., Löwenstein, L., Yarnitsky, D., Tamir, A., & Zimmer, E. Z. (2003) · Anesthesiology · doi:10.1097/00000542-200306000-00018 · Cited by 248 · see citing works
Function of the Male Sex Organs in Heroin and Methadone Users
Cicero, T. J., Bell, R. D., Wiest, W. G., Allison, J. H., Polakoski, K. L., & Robins, E. (1975) · New England Journal of Medicine · doi:10.1056/nejm197504242921703 · Cited by 246 · see citing works
The Role of Interleukin-6 in Nociception and Pain
Jongh, R. F. D., Vissers, K. C. P., Meert, T. F., Booij, L. H. D. J., Deyne, C. S. D., & Heylen, R. J. (2003) · Anesthesia & Analgesia · doi:10.1213/01.ane.0000055362.56604.78 · Cited by 226 · see citing works
Symptomatic hypogonadism in male survivors of cancer with chronic exposure to opioids
Rajagopal, A., Vassilopoulou‐Sellin, R., Palmer, J. L., Kaur, G., & Bruera, E. (2004) · Cancer · doi:10.1002/cncr.20028 · Cited by 206 · see citing works
Role of interleukin-6 in chronic muscle hyperalgesic priming
Dina, O. A., Green, P. G., & Levine, J. D. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.01.006 · Cited by 164 · see citing works
Predicting Postoperative Pain by Preoperative Pressure Pain Assessment
Hsu, Y.-W., Somma, J., Hung, Y.-C., Tsai, P.-S., Yang, C.-H., & Chen, C.-C. (2005) · Anesthesiology · doi:10.1097/00000542-200509000-00026 · Cited by 164 · see citing works
Rosseland, L. A., & Stubhaug, A. (2004) · Pain · doi:10.1016/j.pain.2004.08.028 · Cited by 155 · see citing works
Bhasin, S., Travison, T. G., Storer, T. W., Lakshman, K., Kaushik, M., Mazer, N. A., Ngyuen, A.-H., Davda, M. N., Jara, H., Aakil, A., et al. (2012) · JAMA · doi:10.1001/jama.2012.227 · Cited by 152 · see citing works
Self-citationEdwards, R. R., Mensing, G., Cahalan, C., Greenbaum, S., Narang, S., Belfer, I., Schreiber, K. L., Campbell, C., Wasan, A. D., & Jamison, R. N. (2013) · Journal of Pain and Symptom Management · doi:10.1016/j.jpainsymman.2012.06.016 · Cited by 150 · cited 1× · see citing works
“Cold pain intensity ratings (0-100) were also obtained at 30-second intervals after cold-pressor tests to assess painful aftersensations.(18)”
MethodSelf-citationOpen-label pilot study of testosterone patch therapy in men with opioid-induced androgen deficiency
Daniell, H. W., Lentz, R., & Mazer, N. A. (2006) · The Journal of Pain · doi:10.1016/j.jpain.2005.10.009 · Cited by 135 · see citing works
Low bone density in patients receiving methadone maintenance treatment
Kim, T. W., Alford, D. P., Malabanan, A., Holick, M. F., & Samet, J. H. (2006) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2006.05.027 · Cited by 131 · see citing works
Self-citationElevated Pain Sensitivity in Chronic Pain Patients at Risk for Opioid Misuse
Edwards, R. R., Wasan, A. D., Michna, E., Greenbaum, S., Ross, E. L., & Jamison, R. N. (2011) · Journal of Pain · doi:10.1016/j.jpain.2011.02.357 · Cited by 109 · see citing works
Self-citationProinflammatory cytokines mediating burn-injury pain
Summer, G. J., Romero-Sandoval, E. A., Bogen, O., Dina, O. A., Khasar, S. G., & Levine, J. D. (2007) · Pain · doi:10.1016/j.pain.2007.05.012 · Cited by 108 · see citing works
Hormone replacement therapy in morphine-induced hypogonadic male chronic pain patients
Aloisi, A., Ceccarelli, I., Carlucci, M., Suman, A., Sindaco, G., Mameli, S., Paci, V., Ravaioli, L., Passavanti, G., Bachiocco, V., et al. (2011) · Reproductive Biology and Endocrinology · doi:10.1186/1477-7827-9-26 · Cited by 77 · cited 2× · see citing works
“Opioid-induced androgen deficiency is also associated with reduced quality of life.(2) Previous uncontrolled reports have shown improvement in some aspects of health-related quality of life in men receiving testosterone.”
ALOISI, A. M., CECCARELLI, I., & FIORENZANI, P. (2003) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1286.022 · Cited by 66 · see citing works
Qin, Y., Zhao, Z., Sun, M., Geng, L., Che, L., & Chen, Z.-J. (2011) · Reproductive Biology and Endocrinology · doi:10.1186/1477-7827-9-9 · Cited by 63 · see citing works
Basaria, S. S., Davda, M. N., Travison, T. G., Ulloor, J., Singh, R., & Bhasin, S. (2012) · The Journals of Gerontology Series A · doi:10.1093/gerona/gls138 · Cited by 56 · see citing works
Self-citationCardiovascular Manifestations of Sedatives and Analgesics in the Critical Care Unit
Darrouj, J., Karma, L., & Arora, R. (2008) · American Journal of Therapeutics · doi:10.1097/01.pap.0000249925.76324.47 · Cited by 33 · see citing works
Role of Opioid Antagonists in the Treatment of Women with Glucoregulation Abnormalities
Guido, M., Romualdi, D., & Lanzone, A. (2006) · Current Pharmaceutical Design · doi:10.2174/138161206776055895 · Cited by 28 · see citing works
Bialosky, J. E., Bishop, M. D., Robinson, M. E., Price, D. D., & George, S. Z. (2011) · Manual Therapy · doi:10.1016/j.math.2011.06.003 · Cited by 19 · see citing works
Heroin Dependence Duration Influences the Metabolic Parameters
Pereska, Z., Bozinovska, C., Dimitrovski, C., Cakalarovski, K., Chibishev, A., Zdravkovska, M., Babulovska, A., & Janicevic, D. (2012) · Journal of Addiction Medicine · doi:10.1097/adm.0b013e31826bd76c · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline.
Bhasin, S., Brito, J. P., Cunningham, G. R., Hayes, F. J., Hodis, H. N., Matsumoto, A. M., Snyder, P. J., Swerdloff, R. S., Wu, F. C., & Yialamas, M. A. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-00229 · Cited by 1,736 · see citing works
Self-citationOpioids and their endocrine effects: a systematic review and meta-analysis
de Vries, F., Bruin, M., Lobatto, D. J., Dekkers, O. M., Schoones, J. W., van Furth, W. R., Pereira, A. M., Karavitaki, N., Biermasz, N. R., & Zamanipoor Najafabadi, A. H. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgz022 · Cited by 139 · see citing works
Testosterone and Cardiovascular Risk: Meta-Analysis of Interventional Studies
Corona, G., Rastrelli, G., Di Pasquale, G., Sforza, A., Mannucci, E., & Maggi, M. (2018) · The Journal of Sexual Medicine · doi:10.1016/j.jsxm.2018.04.641 · Cited by 138 · see citing works
Treatment of Men for “Low Testosterone”: A Systematic Review
Huo, S., Scialli, A. R., McGarvey, S., Hill, E., Tügertimur, B., Hogenmiller, A., Hirsch, A. I., & Fugh-Berman, A. (2016) · PLOS ONE · doi:10.1371/journal.pone.0162480 · Cited by 97 · see citing works
Opioid-induced endocrinopathies
Fountas, A., Van Uum, S., & Karavitaki, N. (2020) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(19)30254-2 · Cited by 77 · see citing works
MECHANISMS OF ENDOCRINOLOGY: endocrinology of opioids
Fountas, A., Chai, S. T., Kourkouti, C., & Karavitaki, N. (2018) · European Journal of Endocrinology · doi:10.1530/eje-18-0270 · Cited by 60 · see citing works
Lamprecht, A., Sorbello, J., Jang, C., Torpy, D. J., & Inder, W. J. (2018) · European Journal of Endocrinology · doi:10.1530/eje-18-0530 · Cited by 52 · see citing works
Glintborg, D., Vaegter, H. B., Christensen, L. L., Bendix, E., Graven-Nielsen, T., Andersen, P. G., & Andersen, M. (2020) · European Journal of Endocrinology · doi:10.1530/eje-19-0979 · Cited by 32 · see citing works
Raheem, O. A., Patel, S. H., Sisul, D., Furnish, T. J., & Hsieh, T.-C. (2017) · American Journal of Men's Health · doi:10.1177/1557988316672396 · Cited by 29 · see citing works
“There is increasing evidence suggesting that TST in those patients with OIH can reduce hyperalgesia, improve sexual desire, body composition, and aspects of QoL (Basaria et al., 2015).”
BackgroundInfluentialOpioids and pituitary function: expert opinion
Gadelha, M. R., Karavitaki, N., Fudin, J., Bettinger, J. J., Raff, H., & Ben-Shlomo, A. (2022) · Pituitary · doi:10.1007/s11102-021-01202-y · Cited by 27 · see citing works
Huang, G., Travison, T., Maggio, M., Edwards, R. R., & Basaria, S. (2016) · Clinical Endocrinology · doi:10.1111/cen.13049 · Cited by 26 · see citing works
Self-citationExogenous Opioids and the Human Endocrine System: An Endocrine Society Scientific Statement
Karavitaki, N., Bettinger, J. J., Biermasz, N., Christ-Crain, M., Gadelha, M. R., Inder, W. J., Tsourdi, E., Wakeman, S. E., & Zatelli, M. (2024) · Endocrine Reviews · doi:10.1210/endrev/bnae023 · Cited by 14 · see citing works
Kolind, M. I., Christensen, L. L., Caserotti, P., Andersen, M. S., & Glintborg, D. (2022) · Andrology · doi:10.1111/andr.13147 · Cited by 12 · see citing works
- Authors
- Basaria, S., Travison, T. G., Alford, D., Knapp, P. E., Teeter, K., Cahalan, C., Eder, R., Lakshman, K., Bachman, E., Mensing, G., Martel, M. O., Le, D., Stroh, H., Bhasin, S., Wasan, A. D., & Edwards, R. R.
- Affiliations
- Boston University (US)
- Brigham and Women's Hospital (US)
- University of Pittsburgh (US)
- Corresponding author
- Basaria, Shehzad
- ORCID
- Venue
- Pain
- Published
- 2015-02
- Volume
- 156
- Issue
- 2
- Pages
- 280-288
- ISSN
- 0304-3959 (ISSN-L)
- PMC
- PMC6036339
- OpenAlex
- W2004488462
- Cited by
- 125
- References
- 41
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 8 · 2023: 10 · 2022: 13 · 2021: 12 · 2020: 12 · 2019: 8 · 2018: 16 · 2017: 7 · 2016: 21 · 2015: 4
- FWCI
- 13.87
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Pain (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5p30ag031679-15)
- Clinical and Translational Science Institute, Boston University
- National Institute on Aging (P30-AG031679)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
- Keywords
- testosterone replacement therapy, chronic non-cancer pain, transdermal testosterone gel, pain sensitivity, hyperalgesia, sexual desire, quality of life, body composition, men
- MeSH terms
- Administration, Cutaneous, Adult, Analgesics, Opioid, Androgens, Double-Blind Method, Humans, Male, Middle Aged, Pain, Testosterone, Treatment Outcome
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