What are the recommended steps for a patient on testosterone (hormone replacement therapy) therapy experiencing leg swelling and cough?

Management of Leg Swelling and Cough in a Patient on Testosterone Therapy

Immediately assess hematocrit levels and evaluate for heart failure, as testosterone-induced erythrocytosis is the most likely cause of leg swelling and may contribute to respiratory symptoms through increased blood viscosity. 1

Initial Assessment and Diagnostic Workup

Critical Laboratory Testing

• Measure hematocrit/hemoglobin immediately – testosterone commonly causes erythrocytosis, occurring in 2.8% with low-dose transdermal preparations, 11.3-17.9% with gel preparations, and up to 43.8% with injectable formulations 2, 1, 3
• Check cardiovascular risk factors including history of heart disease, as testosterone may exacerbate underlying cardiovascular conditions that manifest as edema and dyspnea 1
• Obtain chest radiograph to evaluate the cough, as this is recommended for all patients with persistent cough to rule out serious pathology including pneumonia, pulmonary embolism, or heart failure 2

Clinical Examination Priorities

• Assess for signs of heart failure including jugular venous distension, pulmonary crackles, and peripheral edema distribution 1
• Evaluate for deep venous thrombosis as testosterone therapy increases VTE risk, and DVT can present with leg swelling and PE with cough 4
• Determine cough characteristics – acute vs. chronic (>8 weeks), productive vs. dry, and associated symptoms to guide differential diagnosis 2

Immediate Management Based on Hematocrit Results

If Hematocrit Exceeds 54%

Intervention is mandatory with the following options 1:

• Temporarily discontinue testosterone therapy until hematocrit normalizes 1
• Reduce testosterone dose by 50% if therapy must continue 1
• Perform therapeutic phlebotomy or blood donation to reduce blood viscosity and improve symptoms 2, 1

If Hematocrit is Normal but Symptomatic Fluid Retention Present

• Reduce testosterone dose or temporarily discontinue until swelling resolves 1
• Consider formulation switch – transdermal preparations (gels at 5 mg/day) cause erythrocytosis in only 2.8% compared to 43.8% with injectable testosterone 1, 3

Cough-Specific Management

For Acute Cough (<3 weeks)

• Rule out serious illness including pneumonia, pulmonary embolism, or heart failure exacerbation first 2
• If infectious etiology suspected, treat appropriately while continuing testosterone management 2

For Subacute or Chronic Cough (>3 weeks)

• Systematically evaluate for common causes including upper airway cough syndrome (UACS), asthma, non-asthmatic eosinophilic bronchitis (NAEB), and gastroesophageal reflux disease (GERD) 2
• Begin empiric treatment with first-generation antihistamine/decongestant for presumed UACS as initial step 2
• Perform spirometry in all patients with chronic cough to evaluate for asthma or COPD 2

Monitoring Protocol During Treatment Adjustment

Short-Term Follow-Up

• Reassess at 1-2 months after dose reduction or formulation change to evaluate resolution of edema 1
• Remeasure hematocrit/hemoglobin at this visit to ensure normalization if previously elevated 1
• Evaluate cough response to determine if symptoms improve with testosterone modification 2

Long-Term Monitoring

• Monitor every 3-6 months for the first year, then annually if stable 1
• Target mid-range testosterone levels (350-600 ng/dL) rather than high-normal to minimize adverse effects including fluid retention 1

Formulation-Specific Considerations

Injectable testosterone carries the highest risk for erythrocytosis and should be avoided in patients with fluid retention or elevated hematocrit 1, 3. Switch to transdermal gel preparations which have significantly lower rates of erythrocytosis (2.8% vs. 43.8%) and allow easier dose titration 1, 3.

Critical Pitfalls to Avoid

• Do not continue testosterone at current dose if hematocrit exceeds 54% – this increases thrombotic risk and can worsen both leg swelling and respiratory symptoms 2, 1
• Do not attribute all symptoms to testosterone without ruling out serious causes like PE, DVT, or heart failure, especially given the increased VTE risk with testosterone therapy 4
• Do not restart therapy without confirming documented testosterone deficiency (<230 ng/dL or symptomatic levels 231-346 ng/dL), as therapy should not continue in eugonadal men 1
• Do not ignore persistent cough – if it continues after testosterone adjustment, pursue systematic evaluation for UACS, asthma, NAEB, and GERD as these are the most common causes of chronic cough 2

When to Consider Discontinuing Testosterone Therapy

Reassess the indication for therapy if symptoms persist despite dose reduction and formulation change 1. Testosterone therapy should only continue in men with confirmed hypogonadism and documented benefits that outweigh risks 2, 5.