Low Testosterone is Associated with Increased Opioid Requirement and Development of Acute and Chronic Pain after TLIF: A 1:1 Exact Match Analysis

Introduction: Sex hormones, especially androgens such as testosterone, have been implicated in modulation of pain in both animal models as well as human studies. However, the role of testosterone in influencing pain after transforaminal lumbar interbody fusion (TLIF) has not been well described. The objective of this study is to compare pain levels, as measured by morphine milliequivalents (MME), in patients with low testosterone and normal to high testosterone after TLIF.

Methods: Patients who underwent 1-3 level TLIF between 2010-2023 were identified using the PearlDiver Mariner all-claims insurance database. Patients undergoing surgery for tumors, trauma, or infection were excluded. Only male patients were included. Patients with testicular dysfunction were considered to have low testosterone and those without were considered to have normal to high testosterone. 1:1 exact matching was performed using demographic factors and medical comorbidities. The primary outcome measure was the dosage of opioids prescribed, as measured by MME. The secondary outcomes were medical complications, surgical complications, the development of pseudoarthrosis or adjacent segment disease (ASD), and the development of acute or chronic pain.

Results: 1:1 exact matching resulted in two equal groups of 3,238 male patients who had low testosterone or normal to high testosterone and underwent 1-3 level TLIF. Patients with low testosterone were more likely to require higher doses of opioids (> 450 MME) (RR 1.02, 95% CI 1.01-1.04, p< 0.05), and had comparatively greater risk of developing pseudoarthrosis (RR 1.45, 95% CI 1.13-1.89, p< 0.05). Similarly, the risk of transition from acute to chronic pain after surgery was higher in the low testosterone group. (RR 1.54, 95% CI 1.33-1.78, p< 0.05). There were no significant differences in all-cause medical complications between the two patient groups.

Conclusion : After 1:1 matching to control for confounding variables, the results of this study suggest that low levels of testosterone may be associated with inadequate pain control, with an increased requirement for high doses of opioids and development of acute and chronic pain after TLIF. Future studies are needed to corroborate these findings.