The cardiovascular safety story around testosterone therapy has improved over the past two years, but a 2026 orthopedic study has opened a different concern. Research presented at the American Academy of Orthopaedic Surgeons (AAOS) 2026 Annual Meeting found that men who used testosterone in the year before total knee replacement faced significantly higher rates of postoperative complications (AAOS 2026 Annual Meeting Press Kit).
What the Study Found
Researchers compared outcomes among patients undergoing total knee arthroplasty who had filled testosterone prescriptions in the 12 months before surgery and a matched group who had not. Within one year of surgery, TRT users experienced higher rates of several serious complications (AAOS 2026):
- Periprosthetic joint infection: 2.4 percent versus 0.9 percent
- Periprosthetic fracture: 0.7 percent versus 0.2 percent
- Aseptic loosening: 1.0 percent versus 0.5 percent
- Instability: 0.6 percent versus 0.3 percent
- Revision surgery: 1.6 percent versus 1.0 percent
The study also reported higher rates of pneumonia, blood clots, and kidney injury among TRT users in the immediate postoperative period (PRNewswire, 2026).
Why This Might Be Happening
The researchers did not establish a mechanism, but several plausible explanations exist. Testosterone increases red blood cell mass, which can raise the risk of clotting events. It can also influence immune function in complex ways, potentially affecting infection risk. Patients on TRT may also share other risk factors, such as obesity or metabolic syndrome, that independently raise surgical complication rates.
It is also worth noting that this is observational data. The study cannot prove that testosterone caused the higher complication rates. It can only show that the two were associated.
What It Means for Patients Planning Surgery
If you are on TRT and have a knee replacement scheduled, do not stop therapy on your own. Abruptly stopping testosterone has its own risks, including fatigue, mood changes, and rebound symptoms.
Instead, have a clear conversation with both your prescribing physician and your orthopedic surgeon. Together they may decide to pause therapy temporarily before surgery (the optimal window is still being studied, but some surgeons now recommend a hold of several weeks), adjust dosing to the lowest effective amount in the months leading up to surgery, monitor hematocrit more closely since elevated red blood cell mass is a known clotting risk, and optimize other modifiable risk factors including weight, blood sugar, and smoking status.
Broader Implications
This study is a reminder that TRT is a real medical intervention with real effects beyond the symptoms it is prescribed to treat. The improving cardiovascular safety picture should not be confused with a clean bill of health across every clinical setting.
Patients undergoing any major surgery, not just orthopedic procedures, should make sure their surgical team knows they are on testosterone. The risk may not be limited to knee replacement, and surgeons are increasingly attentive to perioperative hormone management.
