A March 2026 study presented at the American Academy of Orthopaedic Surgeons (AAOS) annual meeting analyzed over 13,000 knee replacement patients and found that those who used testosterone replacement therapy in the 12 months before surgery had significantly higher rates of infection, blood clots, kidney injury, and other serious complications.
This is the largest dataset we have linking TRT to surgical outcomes, and it changes the conversation every man on testosterone should have with his surgeon before going under the knife.
Key Takeaways
- TRT patients had 2.7x the sepsis rate and 1.5x the kidney injury rate after knee replacement
- Deep vein thrombosis, pulmonary embolism, and pneumonia rates were all elevated in TRT users
- Complications persisted up to 5 years post-surgery, including higher rates of implant failure
- No guidelines exist yet for TRT perioperative management -- but the data demands a protocol
What the AAOS Study Found
Researchers analyzed post-surgical outcomes for more than 13,000 patients who underwent total knee arthroplasty (TKA). They compared patients who had been on TRT within 12 months of surgery against those who had not.
The results were consistent across nearly every complication category:
| Complication |
TRT Patients |
Non-TRT Patients |
| Pulmonary embolism |
2.6% |
2.0% |
| Deep vein thrombosis |
4.5% |
3.3% |
| Cardiac events |
3.0% |
2.4% |
| Pneumonia |
6.0% |
4.0% |
| Acute kidney injury |
7.9% |
5.2% |
| Sepsis |
2.4% |
0.9% |
These are not small differences. The sepsis rate in TRT patients was nearly three times higher than in non-users. Kidney injury affected nearly 1 in 12 TRT patients versus 1 in 19 non-users.
The long-term data was equally concerning. At five years post-surgery, TRT patients showed higher rates of joint infection, bone fracture around the implant, implant loosening, knee instability, and the need for revision surgery.
Why TRT Raises Surgical Risk
The study didn't establish causation -- it's observational data. But the biological mechanisms are well understood and align with what we know about testosterone's effects on the body.
Hematocrit and Clotting
Testosterone stimulates erythropoiesis -- the production of red blood cells. This is why elevated hematocrit is the most common side effect of TRT and why regular blood monitoring is non-negotiable.
Higher hematocrit means thicker blood. Thicker blood clots more easily. Surgery already creates clot risk through immobilization, tissue damage, and inflammation. Add elevated hematocrit on top of that, and the math becomes unfavorable.
The study's DVT and PE numbers reflect exactly this: TRT patients had roughly 35% higher rates of both compared to non-users.
Immune Modulation
Testosterone has immunosuppressive properties. At physiological levels, this is generally beneficial -- it helps regulate inflammatory responses. But in the perioperative window, any degree of immune suppression can impair wound healing and increase susceptibility to infection.
The 2.7x sepsis rate is the most striking number in the dataset. Sepsis after joint replacement is a catastrophic complication that can lead to implant removal, prolonged hospitalization, and in severe cases, death.
Kidney Stress
Surgery creates significant metabolic stress. Anesthesia, blood loss, fluid shifts, and medication metabolism all tax the kidneys. Testosterone's effect on red blood cell mass increases renal workload even at baseline. The combination appears to push kidney injury rates meaningfully higher.
What This Means for You
If you're on TRT and have surgery planned -- or even think you might need surgery in the next year -- here's what to do.
1. Tell Your Surgeon You're on TRT
This sounds obvious, but clinic surveys consistently show that patients often don't disclose TRT to their surgical team. Testosterone is frequently managed by a separate provider (often a telehealth TRT clinic), and it falls through the cracks in the pre-surgical intake process.
Your surgeon needs to know:
- What form of testosterone you use (injections, gel, pellets)
- Your current dose and frequency
- Your most recent hematocrit level
- How long you've been on TRT
2. Get Pre-Surgical Labs
At minimum, your surgical team should review:
- Complete blood count (CBC) -- hematocrit above 52% is a red flag for elective surgery
- Comprehensive metabolic panel (CMP) -- baseline kidney and liver function
- Coagulation panel (PT/INR, PTT) -- clotting factor status
- Estradiol -- high estradiol independently affects clotting risk
If your hematocrit is elevated, your surgeon or TRT provider may recommend therapeutic phlebotomy or a temporary dose reduction before your procedure.
3. Discuss Whether to Pause TRT
There are no published guidelines for TRT perioperative management. This is a gap the medical community needs to fill. But based on this data, the conversation is worth having.
Factors that might favor a temporary pause:
- Hematocrit above 50%
- History of blood clots or clotting disorders
- Major surgery with prolonged immobilization (joint replacement, spinal fusion)
- Surgery involving implants where infection risk is especially high
Factors that might favor continuing:
- Minor or outpatient procedures with minimal clot risk
- Short-acting testosterone (cypionate or enanthate injections) that will clear within 1-2 weeks
- Well-controlled hematocrit below 48%
If you do pause, understand the timeline. Testosterone cypionate has a half-life of about 8 days, so levels will drop meaningfully within 2-3 weeks of your last injection. Testosterone pellets release slowly and can't be "paused" -- factor this into surgical planning.
4. Optimize Before Surgery
If your procedure is elective and you have 4-8 weeks of lead time:
- Donate blood or get therapeutic phlebotomy to bring hematocrit below 50%
- Check kidney function and address any baseline abnormalities
- Review your estradiol management -- optimize E2 to reduce additional clotting risk
- Discuss DVT prophylaxis with your surgeon -- compression stockings, early mobilization, and possibly anticoagulants
Context: TRT Is Not Unsafe
This study does not mean TRT is dangerous. It means TRT adds a variable that matters in surgical settings.
The TRAVERSE trial -- the largest randomized controlled trial of TRT safety -- established that testosterone therapy does not increase the risk of heart attack, stroke, or cardiovascular death in men with hypogonadism. That finding stands.
What the AAOS data adds is nuance: the perioperative window is a specific, time-limited context where TRT's effects on blood viscosity, immune function, and kidney workload intersect with the physiological stress of surgery. Managing that intersection is straightforward -- it just requires awareness and planning.
Testosterone prescriptions in the U.S. have risen from 7.3 million in 2019 to over 11 million in 2024. As the TRT population grows, more men on testosterone will need surgery. This data should drive protocol development, not fear.
The Bottom Line
If you're on TRT and have surgery on the horizon:
- Disclose everything to your surgical team -- medication, dose, last injection date
- Get labs at least 4 weeks before surgery -- hematocrit, CMP, coagulation, estradiol
- Have the pause conversation -- there's no one-size-fits-all answer, but the question needs asking
- Optimize modifiable risks -- hematocrit, hydration, estradiol, DVT prophylaxis
- Work with a clinic that coordinates care -- the best online TRT clinics will help manage your protocol around surgical events
The study authors called for prospective trials and formal perioperative guidelines. Until those exist, informed patients and communicating providers are the best defense.
References
- American Academy of Orthopaedic Surgeons. "New research links testosterone therapy with serious health risks after total knee replacement surgery." AAOS 2026 Annual Meeting. March 2026.
- Budoff MJ, et al. "Testosterone Treatment and Coronary Artery Plaque Volume in Older Men with Low Testosterone." JAMA. 2017;317(7):708-716.
- Lincoff AM, et al. "Cardiovascular Safety of Testosterone-Replacement Therapy." N Engl J Med. 2023;389(2):107-117.
- Zitzmann M, et al. "Cardiovascular safety of testosterone therapy -- Insights from the TRAVERSE trial and beyond." Andrology. 2026.
- Houghton DE, et al. "Testosterone therapy and venous thromboembolism: A systematic review and meta-analysis." Thromb Res. 2018;172:94-103.
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