Prescription Testosterone Increases the Risk of Reoperation for Infection and All-Cause Reoperation after Primary Total Knee Arthroplasty

Abstract

The rate of total knee arthroplasty (TKA) continues to rise, and with it, the need to identify risk factors for reoperation. Additionally, supplemental testosterone use in male patients has increased across the United States. As more patients taking prescription testosterone replacement therapy (TRT) undergo TKA, there is a need to evaluate TRT as it relates to outcomes following TKA. This study aims to evaluate whether the prescription of supplemental testosterone is a risk factor for reoperation and reoperation for infection following TKA. A retrospective cohort study using a nationwide commercial claims database was conducted. About 76,276 male patients who underwent TKA were identified with a 1.9-year mean follow-up. Reoperations and reoperations for infections were identified using the International Classification of Diseases Tenth Edition (ICD-10) and the Current Procedural Terminology (CPT) codes. Patients were matched based on demographic, geographic, and comorbidities data using Mahalanobis nearest neighbor matching. Statistical analysis was conducted on 3,209 male patients prescribed testosterone and 32,090 not prescribed testosterone. Demographic and comorbidities, including age, location of TKA, length of stay, history of diabetes mellitus, hypertension, hyperlipidemia, obesity, smoking, alcohol, and Charlson Comorbidity Index (CCI) score, were similar (p > 0.05) between male patients prescribed testosterone and men who were not. Men prescribed testosterone had a significantly higher cumulative incidence of reoperation for infection than patients not prescribed testosterone at 1 (p = 0.01), 2 (p < 0.001), 3 (p < 0.001), 4 (p < 0.001), and 5 years postoperatively (p < 0.001). Men prescribed testosterone had a significantly higher cumulative incidence for all-cause reoperation than patients not prescribed testosterone at 1 (p = 0.01), 2 (p = 0.003), 3 (p = 0.01), 4 (p < 0.001), and 5 years postoperatively (p < 0.001). Male patients who were prescribed supplemental testosterone within 1 year prior to primary TKA were at an increased risk for both all-cause reoperation and reoperation due to infection. Surgeons should consider the risks and benefits of testosterone cessation in the perioperative period for patients undergoing TKA.

Keywords

testosterone - total knee arthroplasty - risk factors - infection

Note

This work was performed at the New England Baptist Hospital, 125 Parker Hill Ave, Boston, MA, 02120.

Publication History

Received: 18 October 2024

Accepted: 13 May 2025

Accepted Manuscript online:
14 May 2025

Article published online:
20 June 2025

• References

• 1 Riaz S, Umar M. Revision knee arthroplasty. J Pak Med Assoc 2006; 56 (10) 456-460
• 2 Roman MD, Russu O, Mohor C. et al. Outcomes in revision total knee arthroplasty (Review). Exp Ther Med 2022; 23 (01) 29
• 3 Labek G, Thaler M, Janda W, Agreiter M, Stöckl B. Revision rates after total joint replacement: cumulative results from worldwide joint register datasets. J Bone Joint Surg Br 2011; 93 (03) 293-297
• 4 Upfill-Brown A, Hsiue PP, Sekimura T. et al. Epidemiology of revision total knee arthroplasty in the United States, 2012 to 2019. Arthroplast Today 2022; 15: 188-195.e6
• 5 Jasper LL, Jones CA, Mollins J, Pohar SL, Beaupre LA. Risk factors for revision of total knee arthroplasty: a scoping review. BMC Musculoskelet Disord 2016; 17: 182
• 6 Cohn RM, Ganz MP, Scuderi GR. Testosterone replacement therapy in orthopaedic surgery. J Am Acad Orthop Surg 2024; 32 (08) 331-338
• 7 Lin CY, Casey E, Herman DC, Katz N, Tenforde AS. Sex differences in common sports injuries. PM R 2018; 10 (10) 1073-1082
• 8 Mountjoy M, Sundgot-Borgen J, Burke L. et al. The IOC consensus statement: beyond the Female Athlete Triad–Relative Energy Deficiency in Sport (RED-S). Br J Sports Med 2014; 48 (07) 491-497
• 9 Choong AL, Shadbolt C, Choong E. et al. The impact of sex on the outcomes of prosthetic joint infection treatment with debridement, antibiotics and implant retention: A systematic review and individual patient data meta-analysis. J Am Acad Orthop Surg Glob Res Rev 2022; 6 (11) e22.00102
• 10 Schiffman CJ, Hsu JE, Khoo KJ. et al. Association between serum testosterone levels and Cutibacterium skin load in patients undergoing elective shoulder arthroplasty: A cohort study. JBJS Open Access 2021; 6 (04) e21.00030
• 11 Collins LK, Cole MW, Waters TL, Iloanya M, Massey PA, Sherman WF. Hormone replacement therapy does not eliminate risk factors for joint complications following total joint arthroplasty: A matched cohort study. Pathophysiology 2023; 30 (02) 123-135
• 12 Bhasin S, Brito JP, Cunningham GR. et al. Testosterone therapy in men with hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2018; 103 (05) 1715-1744
• 13 Shoskes JJ, Wilson MK, Spinner ML. Pharmacology of testosterone replacement therapy preparations. Transl Androl Urol 2016; 5 (06) 834-843
• 14 Mulhall JP, Trost LW, Brannigan RE. et al. Evaluation and management of testosterone deficiency: AUA Guideline. J Urol 2018; 200 (02) 423-432
• 15 Rao PK, Boulet SL, Mehta A. et al. Trends in testosterone replacement therapy use from 2003 to 2013 among reproductive-age men in the United States. J Urol 2017; 197 (04) 1121-1126
• 16 Anaissie J, DeLay KJ, Wang W, Hatzichristodoulou G, Hellstrom WJ. Testosterone deficiency in adults and corresponding treatment patterns across the globe. Transl Androl Urol 2017; 6 (02) 183-191
• 17 Sellke N, Omil-Lima D, Sun HH. et al. Trends in testosterone prescription during the release of society guidelines. Int J Impot Res 2024; 36 (04) 380-384
• 18 Coden G, Grant A, Kuznetsov M, Smith EL. Geographical incidence of testosterone supplementation in total hip and knee arthroplasty. J Orthop 2024; 61: 47-53
• 19 Glasheen WP, Cordier T, Gumpina R, Haugh G, Davis J, Renda A. Charlson Comorbidity Index: ICD-9 update and ICD-10 translation. Am Health Drug Benefits 2019; 12 (04) 188-197
• 20 Kong L, Cao J, Zhang Y, Ding W, Shen Y. Risk factors for periprosthetic joint infection following primary total hip or knee arthroplasty: A meta-analysis. Int Wound J 2017; 14 (03) 529-536
• 21 Basques BA, Bell JA, Fillingham YA, Khan JM, Della Valle CJ. Gender differences for hip and knee arthroplasty: Complications and healthcare utilization. J Arthroplasty 2019; 34 (08) 1593-1597.e1
• 22 Elston MJ, Dupaix JP, Opanova MI, Atkinson RE. Cutibacterium acnes (formerly Proprionibacterium acnes) and shoulder surgery. Hawaii J Health Soc Welf 2019; 78 (11, Suppl 2): 3-5
• 23 Matsen III FA, Whitson A, Hsu JE. Preoperative skin cultures predict periprosthetic infections in revised shoulder arthroplasties: A preliminary report. JBJS Open Access 2020; 5 (04) e20.00095
• 24 Kim MK, Patel RA, Shinn AH. et al. Evaluation of gender difference in skin type and pH. J Dermatol Sci 2006; 41 (02) 153-156
• 25 Zouboulis CC, Chen WC, Thornton MJ, Qin K, Rosenfield R. Sexual hormones in human skin. Horm Metab Res 2007; 39 (02) 85-95
• 26 Heckmann N, Sivasundaram L, Heidari KS. et al. Propionibacterium acnes persists despite various skin preparation techniques. Arthroscopy 2018; 34 (06) 1786-1789
• 27 Su F, Cogan CJ, Serna J, Feeley BT, Ma CB, Lansdown DA. Effect of supplemental testosterone use on shoulder arthroplasty infection rates. Semin Arthroplasty 2023; 33 (04) 675-681
• 28 Shigehara K, Izumi K, Kadono Y, Mizokami A. Testosterone and bone health in men: A narrative review. J Clin Med 2021; 10 (03) 530
• 29 Cicuttini FM, Wluka A, Bailey M. et al. Factors affecting knee cartilage volume in healthy men. Rheumatology (Oxford) 2003; 42 (02) 258-262
• 30 Hanna F, Ebeling PR, Wang Y. et al. Factors influencing longitudinal change in knee cartilage volume measured from magnetic resonance imaging in healthy men. Ann Rheum Dis 2005; 64 (07) 1038-1042
• 31 Testa EJ, Albright JA, Hartnett D. et al. The relationship between testosterone therapy and rotator cuff tears, repairs, and revision repairs. J Am Acad Orthop Surg 2023; 31 (11) 581-588
• 32 Albright JA, Lou M, Rebello E. et al. Testosterone replacement therapy is associated with increased odds of Achilles tendon injury and subsequent surgery: a matched retrospective analysis. J Foot Ankle Res 2023; 16 (01) 76
• 33 Dehghan F, Muniandy S, Yusof A, Salleh N. Testosterone reduces knee passive range of motion and expression of relaxin receptor isoforms via 5α-dihydrotestosterone and androgen receptor binding. Int J Mol Sci 2014; 15 (03) 4619-4634
• 34 Dehghan F, Haerian BS, Muniandy S, Yusof A, Dragoo JL, Salleh N. The effect of relaxin on the musculoskeletal system. Scand J Med Sci Sports 2014; 24 (04) e220-e229
• 35 Ardeljan AD, Meneses ZA, Neal BV, Vakharia RM, Roche MW. Increased medical complications, revisions, in-hospital lengths of stay, and cost in patients with hypogonadism undergoing primary total knee arthroplasty. J Arthroplasty 2020; 35 (01) 95-99
• 36 Amory JK, Chansky HA, Chansky KL. et al. Preoperative supraphysiological testosterone in older men undergoing knee replacement surgery. J Am Geriatr Soc 2002; 50 (10) 1698-1701
• 37 Jasuja GK, Bhasin S, Rose AJ. et al. Provider and site-level determinants of testosterone prescribing in the veterans healthcare system. J Clin Endocrinol Metab 2017; 102 (09) 3226-3233
• 38 Scott A, Newson L. Should we be prescribing testosterone to perimenopausal and menopausal women? A guide to prescribing testosterone for women in primary care. Br J Gen Pract 2020; 70 (693) 203-204