Pre-operative injectable testosterone therapy is associated with increased five-year revision risk after total...

Testosterone replacement therapy (TRT) has become increasingly prevalent among men and influences bone metabolism, muscle strength, inflammatory signaling, and pain perception. These factors may affect implant durability and long-term outcomes after primary total shoulder arthroplasty (TSA). While perioperative risks of hormonal therapies have been evaluated in other orthopedic populations, the relationship between pre-operative TRT exposure and long-term TSA outcomes remains poorly understood. The purpose of this study was to evaluate the association between pre-operative injectable TRT use and long-term post-operative outcomes following primary TSA.

A retrospective cohort study was conducted using the TriNetX US Collaborative Network to identify male patients aged ≥18 years who underwent primary TSA between 2005 and 2020, identified by Current Procedural Terminology code 23472. Patients with documented injectable TRT use within one year before surgery were compared with nonusers, and patients with a history of prostate or male breast cancer were excluded. Current Procedural Terminology 23472 captures primary TSA and includes both anatomic and reverse procedures; revision shoulder arthroplasties were not included. One-to-one propensity score matching was performed based on demographics and comorbidities. Five-year post-operative outcomes were assessed using risk ratios (RRs) with 95% confidence intervals (CIs). The Benjamini-Hochberg procedure was applied to control the false discovery rate across outcomes, with significance set at an adjusted P < .05.

Before matching, 36,084 patients met the inclusion criteria; 903 were assigned to the pre-operative injectable TRT cohort and 35,181 to the no-TRT cohort. After 1:1 propensity score matching, 901 patients remained in each cohort. At 5 years, after correction for multiple comparisons, TRT use was associated with higher rates of revision surgery (3.46% vs. 1.23%; RR: 2.82; 95% CI: 1.43-5.57; adjusted P = .006), mechanical complications (8.01% vs. 4.83%; RR: 1.66; 95% CI: 1.14-2.42; adjusted P = .018), and shoulder pain (67.4% vs. 60.0%; RR: 1.12; 95% CI: 1.05-1.20; adjusted P = .006). Opioid use disorder was more frequent among TRT users (2.99% vs. 1.50%; RR: 1.99; 95% CI: 1.02-3.86) but did not remain significant after correction (adjusted P = .067).

Pre-operative injectable TRT use in men undergoing primary TSA was associated with higher 5-year risks of revision surgery, mechanical complications, and shoulder pain. These associations do not establish causation and should be regarded as hypothesis-generating; they support the need for long-term outcome surveillance and perioperative counseling for TSA patients receiving TRT.