Opioid-induced androgen deficiency in men: Prevalence, pathophysiology, and efficacy of testosterone therapy

Opioid analgesics are frequently prescribed for the treatment of chronic pain and are a common cause of male androgen deficiency. Despite its high prevalence, this adverse effect of chronic opioid use remains underappreciated by clinicians. As a result, androgen deficiency remains underdiagnosed and likely undertreated. This focused review discusses the expanding literature on opioid-induced androgen deficiency and the efficacy of testosterone therapy, with a particular focus on its anti-nociceptive effects.

Original and review articles on opioid-induced male androgen deficiency published from 1950 through June 2024 were retrieved from PubMed using the key terms "opioids," "hypogonadism," "low testosterone," and "testosterone therapy." References within the retrieved publications were also researched.

Opioids suppress the gonadal axis mainly by inhibiting GnRH synthesis and secretion. The prevalence of opioid-induced androgen deficiency in men varies between 20% and 80% and is influenced by the type of opioid used, duration of exposure, age of the cohort, and how low testosterone was defined. Limited data from clinical trials suggest that testosterone therapy improves libido, body composition, and certain domains of quality of life. Early evidence also suggests that testosterone has anti-nociceptive properties, confirming findings from preclinical and population studies.

Chronic opioid use is a common but underappreciated cause of androgen deficiency in men. There is a need to raise awareness among clinicians regarding this adverse effect of opioid use. Testosterone therapy could be considered in men with unequivocal androgen deficiency after a thorough clinical evaluation. Ongoing clinical trials will shed further light on the efficacy of testosterone therapy, particularly regarding its anti-nociceptive effects.