Patients with testosterone replacement therapy, or TRT, exposure during the year before a single-level anterior cervical discectomy and fusion, or ACDF, had higher reported odds of three outcomes five years later than a matched cohort without TRT exposure, a retrospective study found. ACDF is a neck-spine operation that removes a disc and fuses one level. The outcomes were pseudoarthrosis, meaning the planned fusion did not fully unite; adjacent segment disease, involving a spinal level next to the fusion; and cervical spine reoperation, meaning another operation. The study reports an association within this patient group, not evidence that TRT caused any of the outcomes.
The differences were reported as odds ratios, a relative comparison between the two cohorts. For pseudoarthrosis, the odds ratio was 1.3, with a 95% confidence interval from 1.0 to 1.8 and a P value of 0.049. For adjacent segment disease, it was 1.7, with a 95% confidence interval from 1.0 to 2.8 and a P value of 0.037. For cervical reoperation, it was 1.5, with a 95% confidence interval from 1.1 to 2.2 and a P value of 0.020. The study does not provide absolute event rates, so these figures do not show how common the outcomes were or the percentage-point difference between the groups.
The difference appeared over time
The study was designed to assess complications at four points: thirty days, one year, two years and five years. Researchers used propensity matching and calculated odds ratios with 95% confidence intervals. In the available results, however, no two-year findings are shown, leaving a gap between the one-year comparisons and the reported five-year outcomes.
Early complications were similar
At thirty days, medical complication rates were similar in the TRT and non-TRT cohorts. The reported comparison had a P value greater than 0.05. At one year, the groups also had similar rates of dysphagia, or swallowing difficulty; dysphonia, or voice difficulty; and venous thromboembolism, or VTE, a blood-clot complication. That comparison also had a P value greater than 0.05.
In the reported results, the difference appeared in three longer-term outcomes rather than in the early medical complications or the one-year swallowing, voice and VTE outcomes. The study therefore presents a mixed picture: similar rates for the short-term outcomes that were reported, alongside higher five-year odds for pseudoarthrosis, adjacent segment disease and cervical reoperation.
Who was included
The analysis used a multi-institutional electronic medical record database of adults undergoing single-level ACDF. After propensity matching, each cohort contained 862 patients. Most participants were male, accounting for 88.2% of the sample. The comparison was between the TRT cohort and patients without TRT exposure.
Patients were excluded if they had previous cervical spine surgery, were under 18, or had a history of spinal neoplasms, trauma, inflammatory conditions or infectious bone conditions. The results therefore apply only to the selected single-level surgical population and cannot automatically be extended to patients outside those criteria.
TRT exposure was defined by treatment during the year before surgery. The supplied analysis does not describe the formulation, dose, duration, adherence or reason for treatment. As a result, the reported associations cannot be tied to a particular testosterone product or treatment pattern.
Why the numbers need careful reading
The study's retrospective, nonrandomized design leaves room for residual confounding, meaning other differences between the groups could have contributed to the results even after matching. The supplied report does not identify the matching covariates, provide balance diagnostics or detail how missing data and follow-up completeness were handled.
Absolute numbers are also missing. The analysis gives relative odds, but not the number of events in each cohort, the event rates or the absolute difference in risk. Without that information, readers cannot tell from the reported odds ratios how common any of the outcomes were or how large the difference was in percentage-point terms.
The authors interpret the findings as an association between TRT and higher five-year rates of pseudoarthrosis, adjacent segment disease and cervical spine reoperation. They suggest the results may help inform people receiving TRT about longer-term risks after ACDF. The study does not test whether changing TRT would prevent a complication.
The study datasets are available from the corresponding author on reasonable request, and the authors declare no competing interests.
Paper data and sources
Original title: The impact of testosterone replacement therapy on clinical outcomes after anterior cervical discectomy and fusion: a propensity-matched cohort study.
Authors: Robert J Ferdon, Jacob Peller, Sohaib Z Hashmi et al.
Journal/Repository: European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society
Status: Peer-reviewed
First online: 2026-08-21
DOI: 10.1007/s00586-026-10296-6
Original paper · Full text