Management of Leg Swelling and Cough in Patients on Testosterone Therapy

Initial Assessment and Diagnostic Workup

The American College of Physicians recommends immediately assessing hematocrit levels and evaluating 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
Measure hematocrit/hemoglobin immediately, as 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
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 3

Assess for signs of heart failure, including jugular venous distension, pulmonary crackles, and peripheral edema distribution 1
Determine cough characteristics – acute vs. chronic (>8 weeks), productive vs. dry, and associated symptoms to guide differential diagnosis 4, 3

If hematocrit exceeds 54%, intervention is mandatory, with options including temporarily discontinuing testosterone therapy, reducing testosterone dose by 50%, or performing therapeutic phlebotomy or blood donation to reduce blood viscosity and improve symptoms 1, 2

For acute cough (<3 weeks), rule out serious illness, including pneumonia, pulmonary embolism, or heart failure exacerbation first 4
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) 4
Perform spirometry in all patients with chronic cough to evaluate for asthma or COPD 3

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 4

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

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 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 4

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 5