Opioid-Induced Hypogonadism in the United States

Objective: To examine the incidence of screening, diagnosis, and treatment of hypogonadism among men treated with opioids in the United States. Patients and Methods: Using one of the nation's largest commercial insurance databases, we identified 53,888 men aged 20 years or older who had 90 or more days of opioid prescriptions in a single 12-month period between January 1, 2010, and December 31, 2017, with no history of hypogonadism or testosterone therapy in the preceding 12 months. We matched this cohort to 53,888 men with 14 or fewer days of opioid prescriptions based on age, opioid initiation date, opioid indication, and comparable exclusion criteria. We assessed whether men, 14 or fewer days after initiation of opioid treatment, received a serum testosterone test, a diagnosis of hypogonadism, or a prescription for testosterone therapy. All men were followed up until they lost coverage from the commercial insurance plan, experienced one of the study outcomes, or the end of study (December 31, 2017). Results: In the multivariable analyses—adjusting for age, year of opioid initiation, region, comorbid disease, glucocorticoid use, and health care utilization—the 53,888 prolonged opioid users, in comparison with 53,888 short-term users, had an increased incidence of serum testosterone screening (5991 [17.15%; 95% CI, 16.70%-17.61%] vs 3514 [11.55%; 95% CI, 11.11%-12.01%] at 5 years; hazard ratio [HR], 1.46; 95% CI, 1.38-1.55), hypogonadism diagnosis (3125 [9.44%; 95% CI, 9.09%-9.80%] vs 1421 [4.85%; 95% CI, 4.55%-5.16%; HR, 1.74; 95% CI, 1.60-1.90]), and receipt of testosterone therapy (1919 [5.76%; 95% CI, 5.49%-6.05%] vs 631 [2.21%; 95% CI, 2.04%-2.43%; HR, 2.41; 95% CI, 2.13-2.74]). Each of these findings persisted across multiple sensitivity analyses. Conclusion: Prolonged opioid exposure was associated with increased rates of screening, diagnosis, and treatment for opioid-induced hypogonadism, but these rates were much lower than expected based on previous serum-based studies.