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The use of testosterone replacement therapy (TRT) in men and women has soared in recent years, with prescriptions rising from 7.3 million in 2019 to more than 11 million in 2024.

A large-scale study presented at the 2026 Annual Meeting of the American Academy of Orthopaedic Surgeons points to the health risks of this trend for those who undergo total knee arthroplasty (TKA), although more research is needed to establish testosterone as a cause of serious postoperative issues.

The researchers retrospectively reviewed data on more than 13,000 adult patients who underwent primary TKA before February 2020 through 5 years of follow-up using the TriNetX national electronic health record database. The study is believed to be the largest of its kind to date, and the only one to include near-equal numbers of men and women.

It builds on earlier work that examined possible links between preoperative testosterone replacement therapy and patient outcomes after total shoulder arthroplasty. The shoulder study helped expand how exogenous hormone therapy might influence joint replacement outcomes in different parts of the body.

Study Findings

In the knee replacement study, patients with a history of septic arthritis, osteonecrosis, or chronic bone fractures were excluded. Patients were ranked according to their use of testosterone in the 12 months before surgery. Propensity score matching (1:1) was used to balance demographic and clinical variables, including age, sex, race, obesity, smoking, cardiovascular disease, diabetes, chronic kidney disease, and hypogonadism.

Highlights of the findings include:

• At 90 days, TRT users had higher rates of pulmonary embolism (PE) (1.6% vs. 1.2%; P = 0.041), pneumonia (3.3% vs. 1.9%; P <0.001), acute kidney injury (AKI) (4.2% vs. 2.9%; P < 0.001), and sepsis (1.9% vs. 1.1%; P < 0.001).
• At 1 year, TRT was associated with increased rates of PE (2.6% vs. 2.0%; P < 0.015), deep vein thrombosis (DVT) (4.5% vs. 3.3%; P < 0.001), cardiac events (3.0% vs. 2.4%; P =0.018), pneumonia (6.0% vs. 4.0%; P < 0.001), AKI (7.9% vs. 5.2%; P < 0.001), and sepsis (2.4% vs. 0.9%; P < 0.001).
• Periprosthetic complications at 1 year were also significantly higher in TRT users, including periprosthetic joint infection (PJI) (2.4% vs. 0.9%; P <0.001), periprosthetic fracture (0.7% vs. 0.2%; P < 0.001), aseptic loosening (1.0% vs. 0.5%; P = 0.001), instability (0.6% vs. 0.3%; P = 0.020), and revision surgery (1.6% vs. 1.0%; P = 0.002).
• These complications remained elevated at 5years, with TRT patients experiencing higher rates of PJI (4.3% vs. 1.9%; P < 0.001), periprosthetic fracture (1.6% vs. 0.6%; P <0.001), loosening (2.7% vs. 1.3%; P < 0.001), instability (1.7% vs. 0.8%; P < 0.001), and revision (4.1% vs. 2.7%; P <0.001).

Along with higher risks for blood clots, sepsis and other life-threatening conditions, the new study showed that patients on TRT are more likely to need revision surgery after the implant loosens or osseointegration does not occur. Post-surgical infections of the knee are also likelier when patients take testosterone before undergoing TKA.

Earlier studies of testosterone and knee surgery outcomes were smaller and more focused on short-term health issues, the researchers said. The scope of the new study, and the inclusion of a large female cohort, add significance to the findings. Women currently make up 60% of all TKA surgeries in the U.S., and this number is expected to grow.

Source

Omurzakov A, Omurzakov AM, Bhatti P, Debbi EM, Gausden E, Chalmers B. Preoperative Testosterone Replacement Therapy Is Associated with Increased Complication Risk After Total Knee Arthroplasty: A Propensity-Matched Analysis of 13,250 Patients. Presented at the Annual Meeting of the American Academy of Orthopaedic Surgeons, March 2-6, 2026, New Orleans, Louisiana.