What are the vascular effects of testosterone therapy?

Vascular Effects of Testosterone Therapy

Testosterone therapy appears to have a neutral or potentially beneficial effect on cardiovascular health, with physiologic replacement doses showing no significant increase in major adverse cardiovascular events. 1

Cardiovascular Effects

Direct Vascular Actions

• Testosterone has vasodilatory properties:
  • Increases coronary artery diameter and blood flow 1
  • Improves cardiac ischemia and symptoms in men with chronic stable angina 2
  • Reduces peripheral vascular resistance in chronic heart failure 2
  • Acts as an L-calcium channel blocker and activates potassium channels in vascular smooth muscle cells 2

Cardiovascular Risk

• The most recent and highest quality evidence from the TRAVERSE trial (2023) demonstrated:
  • No increase in major adverse cardiac events with testosterone therapy compared to placebo (HR 0.96; 95% CI 0.78-1.17) 3
  • No significant difference in death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke 3
  • Higher incidence of atrial fibrillation, acute kidney injury, and pulmonary embolism in the testosterone group 3

Lipid Profile Effects

• Physiologic replacement doses have minimal impact on lipid profiles:
  • No change or minimal reduction in HDL cholesterol 1
  • Often accompanied by reduction in total cholesterol 1
  • LDL levels typically unchanged or reduced 1
  • Supraphysiologic doses (particularly oral nonaromatizable androgens) may lower HDL levels 1

Hemostasis and Thrombosis

• Complex effects on coagulation factors:
  • Decreases in prothrombotic factors, prothrombinase activity, proteins C and S 1
  • Increases in antithrombin III activity and fibrinolytic activity 1
  • No effect on platelet activity 1
  • FDA label warns of venous thromboembolism risk 4

Clinical Implications

Patient Counseling

• Prior to initiating treatment, patients should be informed that current evidence cannot definitively state whether testosterone therapy increases or decreases cardiovascular risk 1
• Patients should be advised to report any cardiovascular symptoms during follow-up visits 1

Monitoring Recommendations

• Regular monitoring of:
  • Lipid profile 4
  • Hemoglobin and hematocrit (erythrocytosis risk varies by administration route: 3-18% with transdermal, up to 44% with injection) 1
  • Blood pressure and signs of fluid retention 1

Dosing Considerations

• Target testosterone levels in the middle tertile of the normal reference range (450-600 ng/dL) 1
• Use minimal dosing necessary to achieve symptom relief 1
• Different formulations have varying systemic exposure and potential side effects 4

Common Pitfalls and Caveats

1. Conflicting evidence interpretation: Older studies (like the 2013 VA study) suggested increased cardiovascular risk 5, but the recent TRAVERSE trial provides stronger evidence of cardiovascular safety 3

2. Inappropriate dosing: Supraphysiologic doses may have different risk profiles than physiologic replacement doses 1

3. Patient selection: Safety data primarily applies to men with documented testosterone deficiency, not "age-related hypogonadism" 4

4. Pre-existing conditions: Use caution in patients with cardiac, renal, or hepatic disease due to potential fluid retention 4

5. Monitoring gaps: Failure to regularly assess cardiovascular parameters, lipids, and hematocrit may miss developing complications 1, 4

In conclusion, when used appropriately at physiologic replacement doses in men with documented testosterone deficiency, testosterone therapy appears to have a neutral cardiovascular risk profile based on the most recent high-quality evidence, with potential benefits on vascular function in some patients.