In a patient who recently underwent surgery, does exogenous testosterone affect wound healing or increase thrombosis risk, and should it be held perioperatively?

Exogenous Testosterone and Perioperative Management

Exogenous testosterone does not need to be discontinued before surgery, as current evidence demonstrates no increased risk of postoperative complications, thromboembolism, or mortality when testosterone therapy is continued perioperatively. 1, 2

Key Evidence Supporting Continuation

Thrombotic Risk

• A large propensity-matched study of 947 men on testosterone replacement therapy undergoing noncardiac surgery found no increased risk of deep venous thrombosis (2.0% vs 1.7%), pulmonary embolism (0.5% vs 0.7%), or stroke (2.0% vs 2.1%) compared to controls 2
• The 2023 TRAVERSE trial demonstrated that testosterone therapy does not increase stroke risk, even in men with pre-existing cardiovascular disease 3
• Transgender men continuing testosterone therapy before masculinizing chest surgery showed no thromboembolic complications in a multicenter retrospective study 4

Cardiovascular and Mortality Outcomes

• The same large surgical cohort found no difference in postoperative in-hospital mortality (1.3% vs 1.1%, OR 1.17,99% CI 0.51-2.68) or myocardial infarction (0.2% vs 0.6%) between testosterone users and non-users 2
• The American College of Physicians guideline review found no significant increase in cardiovascular events with testosterone therapy, though this was low-certainty evidence 5

Wound Healing Considerations

The evidence on wound healing is mixed and context-dependent:

• Transgender patients: A multicenter study of 236 patients undergoing masculinizing chest surgery found no significant difference in postoperative bleeding/hematoma (7.2% overall), seroma (2.1%), infection (1.3%), or nipple graft failure (0.4%) between those who continued versus discontinued testosterone 4

• Animal model concerns: A mouse model showed exogenous testosterone at supraphysiological doses impaired wound healing with increased inflammatory cytokines and macrophage proliferation 6. However, another rat study found supraphysiological testosterone improved granulation tissue maturation through enhanced angiogenesis 7

• Clinical translation: The conflicting animal data has not translated to increased wound complications in human surgical studies 4, 2

Perioperative Management Algorithm

For Testosterone Suppression Therapy (Anti-androgens)

• Continue spironolactone perioperatively without interruption 1
• This applies to transgender women and other patients on anti-androgen therapy 1

For Testosterone Replacement Therapy

• Continue testosterone therapy perioperatively in most patients 1, 2
• Transdermal formulations are preferred over intramuscular due to lower erythrocytosis risk (15.4% vs 43.8%) 5
• Routine discontinuation lacks supporting evidence and may cause psychological harm, particularly in transgender patients 1

High-Risk Exceptions Requiring Discussion

Consider individualized risk-benefit discussion for testosterone continuation in patients with:

• Recent venous thromboembolism (within 3 months) 5
• Recurrent VTE history or known thrombophilia 5
• Active malignancy with high thrombotic risk 5
• Concurrent multiple cardiovascular risk factors 5

Even in these high-risk scenarios, the decision should weigh the lack of evidence supporting routine discontinuation against theoretical concerns 1, 2

Critical Pitfalls to Avoid

• Do not routinely discontinue testosterone based on outdated concerns about wound healing or thrombosis—the human surgical data does not support this practice 4, 2

• Do not extrapolate animal model data showing impaired wound healing to clinical practice, as human studies have not confirmed these findings 6, 4

• Do not use intramuscular testosterone formulations in patients with elevated baseline thrombotic risk—transdermal preparations carry significantly lower erythrocytosis risk 5

• Do not apply general VTE prophylaxis guidelines as a reason to stop testosterone—standard chemical thromboprophylaxis should be initiated on postoperative day 1 regardless of testosterone status 8

Monitoring Considerations

• Ensure standard VTE prophylaxis with mechanical compression and pharmacologic prophylaxis (starting postoperative day 1) per surgical risk stratification 8
• Monitor hematocrit if using intramuscular testosterone formulations, as erythrocytosis increases thrombotic risk 3, 5
• For transgender patients, continuation of hormone therapy supports psychological well-being during the perioperative period 1