Could the new‑onset edema in a man receiving testosterone injection therapy be due to the hormone treatment rather than his recent postoperative state?

Edema in a Patient on Testosterone Injections

Yes, testosterone injections can cause edema and are the most likely explanation for new-onset swelling in this clinical scenario, though postoperative fluid retention should also be considered.

Testosterone as the Primary Cause

Mechanism and Incidence

• Testosterone therapy causes fluid retention through sodium and water reabsorption in the kidneys, leading to edema that may be particularly problematic in men with pre-existing cardiac, renal, or hepatic disease 1
• The FDA label explicitly warns that "edema, with or without congestive heart failure, may be a serious complication in patients with pre-existing cardiac, renal or hepatic disease" when using intramuscular testosterone 1
• Injectable testosterone formulations produce supraphysiologic peak serum levels 2–5 days after injection, which may exacerbate fluid retention compared to transdermal preparations 2

Clinical Presentation

• Fluid retention from testosterone is typically mild and generalized, but leg swelling is a common manifestation 2
• The edema may indicate testosterone-induced erythrocytosis contributing to symptoms through increased blood viscosity, particularly if hematocrit has risen above 50% 2

Risk Factors

• Men with congestive heart failure or renal insufficiency are at highest risk for clinically significant fluid retention on testosterone therapy 2
• Older patients and those with cardiovascular disease face greater complications from fluid retention due to elevated blood viscosity 2

Distinguishing Testosterone-Related from Postoperative Edema

Timing Considerations

• If edema appeared within days of the most recent testosterone injection (particularly days 2–5 when serum levels peak), testosterone is the more likely cause 2
• If edema developed immediately postoperatively and has persisted, surgical factors may predominate, though testosterone could be exacerbating the condition 3

Postoperative Context

• Testosterone use does not increase the risk of postoperative cardiovascular events, deep venous thrombosis, or pulmonary embolism in men undergoing noncardiac surgery 3
• However, the combination of postoperative fluid shifts and testosterone-induced sodium retention could produce additive edema 1

Immediate Management Algorithm

Step 1: Assess Severity and Complications

• Measure hematocrit immediately—if >54%, withhold testosterone and consider therapeutic phlebotomy 2
• Evaluate for signs of congestive heart failure (dyspnea, orthopnea, jugular venous distension, pulmonary rales) 1
• Check for unilateral vs. bilateral edema to exclude deep venous thrombosis, though testosterone does not increase DVT risk 3

Step 2: Modify Testosterone Therapy

• Temporarily withhold the next testosterone injection to allow fluid status to normalize 1
• When restarting, reduce the dose by 25–50% or switch from injectable to transdermal testosterone gel, which produces more stable serum levels and less fluid retention 2, 4
• Target mid-normal testosterone levels (450–600 ng/dL) rather than upper-normal ranges to minimize adverse effects 2, 4

Step 3: Symptomatic Treatment

• Initiate or optimize diuretic therapy if cardiac or renal disease is present 1
• Restrict dietary sodium intake 1
• Elevate legs and use compression stockings for symptomatic relief 2

Step 4: Monitor and Reassess

• Recheck hematocrit 2–3 months after dose adjustment 2, 4
• If edema persists despite testosterone modification, investigate other causes (cardiac, renal, hepatic, venous insufficiency) 1
• If edema resolves after withholding testosterone but recurs with rechallenge, consider discontinuing therapy or switching to transdermal formulations 2, 4

Critical Pitfalls to Avoid

• Do not ignore mild edema in patients with cardiovascular risk factors—even modest fluid retention can precipitate heart failure in susceptible individuals 1
• Do not continue full-dose injectable testosterone when symptomatic edema develops—dose reduction or formulation change is mandatory 2, 1
• Do not assume edema is purely postoperative without considering testosterone's contribution—the timing relative to injections is key 2, 3
• Do not overlook erythrocytosis as a contributor—elevated hematocrit (>50%) increases blood viscosity and can manifest as leg swelling 2

Long-Term Considerations

• Injectable testosterone carries a 43.8% risk of erythrocytosis compared to 15.4% with transdermal preparations, making formulation choice critical for patients prone to fluid retention 2
• If the patient has underlying cardiac, renal, or hepatic disease, transdermal testosterone gel is strongly preferred over injections to minimize fluid retention risk 2, 4, 1
• Reevaluate whether testosterone therapy is providing meaningful clinical benefit (improvement in sexual function and libido)—if not, discontinuation should be considered at 12 months 2, 4