A large-scale study presented at the American Academy of Orthopaedic Surgeons annual meeting found that patients taking testosterone replacement therapy (TRT) before total knee replacement surgery face substantially higher risks for serious complications, including blood clots, infections, and organ damage. The research analyzed over 13,000 patients and is believed to be the largest study of its kind to include nearly equal numbers of men and women. Why Is This Study Important for Testosterone Users? Testosterone replacement therapy has exploded in popularity over the past five years. Prescriptions jumped from 7.3 million in 2019 to more than 11 million in 2024, according to the research. The hormone is prescribed to men for low testosterone and to women to improve sex drive, build muscle, and manage menopausal symptoms. With knee replacement surgeries expected to exceed one million procedures annually by 2030, and women now accounting for 60 percent of all knee replacements in the United States, understanding how testosterone affects surgical outcomes has become increasingly urgent. The study, conducted by twin brothers Argen and Arsen Omurzakov, both third-year medical students, reviewed patient data from before February 2020 through five years of follow-up using a national electronic health record database. Researchers carefully matched patients on factors like age, sex, race, obesity, smoking status, cardiovascular disease, diabetes, and chronic kidney disease to ensure fair comparisons. What Specific Complications Did Testosterone Users Experience? The findings were striking across multiple time points. At 90 days after surgery, testosterone users experienced significantly higher rates of several serious conditions: - Pulmonary Embolism: Blood clots in the lungs occurred in 1.6 percent of testosterone users compared to 1.2 percent of non-users - Pneumonia: Lung infections developed in 3.3 percent of testosterone users versus 1.9 percent of controls - Acute Kidney Injury: Kidney damage occurred in 4.2 percent of testosterone users compared to 2.9 percent of non-users - Sepsis: This life-threatening blood infection developed in 1.9 percent of testosterone users versus 1.1 percent of controls By one year after surgery, the differences became even more pronounced. Testosterone users had higher rates of deep vein thrombosis (blood clots in the legs) at 4.5 percent versus 3.3 percent, cardiac events at 3.0 percent versus 2.4 percent, and pneumonia at 6.0 percent versus 4.0 percent. Acute kidney injury affected 7.9 percent of testosterone users compared to 5.2 percent of non-users, and sepsis occurred in 2.4 percent of testosterone users versus just 0.9 percent of controls. Perhaps most concerning for long-term outcomes, testosterone users also experienced significantly higher rates of complications directly related to the knee implant itself. These included periprosthetic joint infections (infections around the artificial joint) at 2.4 percent versus 0.9 percent at one year, and periprosthetic fractures (breaks in bone near the implant) at 0.7 percent versus 0.2 percent. Implant loosening and instability were also more common in testosterone users. These complications persisted at the five-year mark. Testosterone users experienced periprosthetic joint infections at 4.3 percent compared to 1.9 percent in non-users, fractures at 1.6 percent versus 0.6 percent, loosening at 2.7 percent versus 1.3 percent, and instability at 1.7 percent versus 0.8 percent. Revision surgery, needed when the implant fails or complications develop, was required in 4.1 percent of testosterone users versus 2.7 percent of non-users. How Might Testosterone Affect Surgical Recovery? Researchers offered several biological explanations for why testosterone users faced higher complication rates. "Studies also suggest that testosterone influences the way our bones naturally rebuild themselves over time," stated Arsen Omurzakov. Arsen Omurzakov, Third-Year Medical Student at Weill Cornell Medical College "Testosterone levels may also affect the immune system and the microbiomes that affect the immune system, healing and other key functions in the body," added Argen Omurzakov. Argen Omurzakov, Third-Year Medical Student at Case Western Reserve University The hormone has already been linked in previous research with increased blood clot risk. The new findings suggest testosterone may also interfere with how the body heals after surgery, potentially by affecting bone integration with the artificial joint and weakening immune function during the critical recovery window. What Should Patients Consider Before Surgery? While the study establishes a strong association between testosterone use and surgical complications, researchers emphasized that more work is needed to definitively prove testosterone causes these problems. However, the scope and size of this investigation, combined with the inclusion of a large female cohort, adds significant weight to the findings. This is the first major study to examine testosterone's effects in both men and women undergoing knee replacement. Dr. Brian Chalmers, the senior author of the study, noted the urgency of understanding these risks. "With more people taking this hormone than ever, and TKA surgeries expected to exceed one million per year by 2030, we wanted to dive deeper into the question of testosterone's post-surgical effects," said Dr. Brian Chalmers. Dr. Brian Chalmers, Senior Author of the Study The research builds on earlier work examining testosterone's effects after shoulder replacement surgery, suggesting that hormone therapy may influence joint replacement outcomes across different parts of the body. Steps to Take If You Use Testosterone and Need Surgery - Discuss with Your Surgeon: If you take testosterone and are scheduled for knee replacement or other joint surgery, have an explicit conversation with your orthopedic surgeon about the risks identified in this research before your procedure - Review Your Medications: Work with your prescribing physician to understand whether continuing testosterone therapy right up to surgery is necessary, or whether temporarily pausing the hormone might reduce your complication risk - Ask About Monitoring: Request enhanced post-operative monitoring for blood clots, infections, and kidney function if you cannot discontinue testosterone before surgery - Get a Second Opinion: Consider consulting with another orthopedic surgeon experienced in managing high-risk patients if you have concerns about your individual risk profile This research represents an important safety signal for the millions of people currently using testosterone therapy. While the hormone provides real benefits for muscle building, bone health, and sexual function, patients and doctors must now weigh these benefits against the newly documented surgical risks, particularly for those facing joint replacement procedures.
