Response to Letter to the Editor Regarding “Testosterone Replacement Therapy in Posterior Lumbar Fusion Patients: A Propensity Score-Matched Analysis of Long-Term Outcomes”

Dear Editor.

We thank the authors for their thoughtful comments regarding our study, “Testosterone Replacement Therapy in Posterior Lumbar Fusion Patients: A Propensity Score-Matched Analysis of Long-Term Outcomes. ¹ ” We appreciate their recognition of the clinical relevance of this question and agree that the findings of our study should be interpreted within the context of the inherent limitations of large retrospective databases.

The authors appropriately highlight the nonspecific nature of revision posterior lumbar fusion as an endpoint. As they note, our analysis was unable to determine the specific indication for revision surgery, including whether revision was performed for adjacent segment disease, recurrent stenosis, persistent symptoms, implant-related complications, or other factors. Similarly, the TriNetX database does not provide the operative reports, detailed imaging findings, or patient-reported outcomes necessary to adjudicate the clinical indication for revision. We acknowledge these limitations in the discussion of our manuscript and agree that they preclude more granular interpretation of the observed association between TRT exposure and revision surgery.

We similarly recognize the limitations of our TRT exposure definition. Identification of TRT use within the year preceding surgery does not allow for assessment of formulation, dosage, route of administration, duration of treatment, adherence, serum testosterone levels, or perioperative continuation or discontinuation of therapy. Additionally, the indication for TRT and other potentially relevant patient-level factors cannot be reliably characterized within the database. These considerations are particularly important when attempting to determine whether the observed association reflects a direct effect of TRT or instead identifies a patient population with other characteristics that may influence long-term outcomes.

Importantly, our findings were not intended to establish a direct adverse effect of TRT on fusion biology or to suggest that TRT causes postoperative revision. Rather, we believe the utility of this study lies in identifying a previously understudied association within a large, propensity score-matched cohort. The absence of a significant difference in coded pseudarthrosis or implant displacement in our analysis further underscores that the observed revision association should not be interpreted as evidence of impaired fusion or mechanical failure attributable to TRT. As the authors appropriately state, these findings are hypothesis-generating and should serve as a starting point for further investigation.

Future prospective studies with more granular clinical data will be important to clarify this relationship. In particular, evaluation of TRT formulation, dosage, duration, serum testosterone levels, timing of therapy relative to surgery, and perioperative management, along with detailed radiographic assessment, fusion characteristics, patient-reported outcomes, and adjudicated indications for revision, may help determine the mechanisms underlying the association observed in our study. Such investigations may ultimately clarify whether TRT itself represents a modifiable risk factor or whether TRT use serves primarily as a marker of other patient characteristics associated with long-term outcomes following lumbar fusion.

We again thank the authors for their thoughtful discussion and for highlighting important avenues for future research. We agree that additional prospective and clinically granular investigation is necessary before these findings should be translated into specific recommendations regarding TRT management, preoperative counseling, or postoperative surveillance.

ORCID iDs

Mark Miller https://orcid.org/0009-0005-4936-2832

Hunter Smith https://orcid.org/0009-0009-8217-9051

Omar Sbaih https://orcid.org/0009-0008-0768-9097

Nithin Gupta https://orcid.org/0000-0002-6696-8984

Consent to Participate

The use of entirely de-identified records qualified this study as non-human research and is therefore exempt from institutional review board oversight.

Funding: The authors did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Disclosures: The authors certify that there are no financial or non-financial conflicts of interest regarding the material discussed in the manuscript.