Testosterone Therapy Linked to Surgical Risks
New research links testosterone replacement therapy (TRT) with a higher rate of complications after total knee replacement surgery. The large-scale study, presented at the AAOS annual meeting, is the first to include comparable numbers of both men and women.
The study, conducted by twin brothers Argen and Arsen Omurzakov, medical students at Case Western Reserve University and Weill Cornell Medical College respectively, analyzed data from over 13,000 patients. It is the largest study of its kind to include a near-equal number of men and women. The research team, including senior author Dr. Brian Chalmers, used a propensity-matched analysis of 13,250 patients to compare outcomes for those who had used TRT within a year of surgery and those who had not. Within 90 days of total knee arthroplasty, patients on TRT faced significantly higher risks for several serious complications. This included a 1.8 times greater risk of pneumonia and sepsis, a 1.5 times increased risk of acute kidney injury, and a 1.4 times higher risk of pulmonary embolism. The elevated risks persisted and evolved long after the initial surgery. At the five-year mark, TRT use was associated with a 2.7 times higher risk of periprosthetic fractures and a 2.3 times increased risk of periprosthetic joint infections. The likelihood of needing a revision surgery was also 1.5 times greater for the TRT cohort. Researchers suggest several potential biological mechanisms for these findings. Higher testosterone levels have been linked to increased loads of *Cutibacterium* on the skin, a bacterium implicated in prosthetic joint infections. Additionally, TRT may contribute to a higher risk of blood clots by causing polycythemia, a condition characterized by an increased concentration of red blood cells. These findings come as TRT prescriptions have seen a dramatic rise, increasing from 7.3 million in 2019 to over 11 million in 2024. While officially approved for treating hypogonadism, a condition causing low testosterone, it is also used off-label by both men and women to improve sex drive, build muscle mass, and manage menopausal symptoms. In light of the study's results, the authors suggest surgeons should discuss the risks and benefits of pausing testosterone therapy in the period surrounding a total knee replacement to potentially mitigate these adverse outcomes.
