Given the absence of evidence-based guidelines for the diagnosis of OPIAD, many sequelae remain unrecognized or are attributed to chronic pain. The authors noted that “the experience of chronic pain itself has also been associated with androgen deficiency, confounding the association of low testosterone with opioid pain medication use and raising the question of whether androgen deficiency is also associated with pain sensitivity and perception.”

To diagnose patients with OPIAD, testosterone deficiency is based on symptoms and serum testosterone levels, “measured by initial and repeat morning total testosterone level by a reliable assay with free testosterone and sex hormone-binding globulin as indicated by clinical circumstances.” The International Congress of Sexual Medicine and Endocrine Society guidelines generally accepted lower limit of normal total testosterone is 300 to 350ng/dL. Men with total testosterone levels <230ng/dL usually benefit from testosterone treatment.

The study noted the “paucity” of prospective trials with respect to the most effective management strategies for this population. Therefore, the optimal approach to patients with OPIAD is a multidisciplinary care team approach that includes urology and pain management physicians.


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First-line treatment may include diet and exercise and decreased opioid dosage; however, in many cases, it is not possible to stop opioid medication altogether. Alternative OPIAD treatment options include cycling to different opioids; incorporating non-opioid treatments, such as NSAIDs or novel agents; or avoiding long-acting opioids. “There is some evidence that certain opioids may promote hypogonadism to a greater extent than others,” the study noted.

The authors identified 428 “unique publications” that evaluated TRT in patients with OPIAD from January 1960 to May 2016. Of these, 6 studies were included in their review: a prospective randomized double-blind placebo-controlled trial with two published studies, two prospective trials, and two other studies. The type of opioids used included hydrocodone, morphine, hydromorphone, buprenorphine, codeine, propoxyphene, oxymorphone, tramadol, fentanyl, and methadone. The testosterone preparations included transdermal gel and patch, and depot testosterone undecanoate and enanthate.

These studies suggest transdermal or injectable TRT is safe and effective; “however, the optimal testosterone preparation for OPIAD treatment has yet to be determined,” the study noted. “The benefits of TRT in OPIAD may outweigh potential risks in many circumstances given the significant morbidity and quality of life issues potentially facing those with hypogonadism, chronic pain, and chronic opioid use.”