What is the maximum hematocrit (Hct) level allowed for blood donation in individuals undergoing Testosterone Replacement Therapy (TRT)?

Hematocrit Thresholds for Blood Donation During Testosterone Replacement Therapy

Blood donation is recommended when hematocrit exceeds 54% in individuals on testosterone replacement therapy (TRT), as this is the threshold at which intervention is warranted to reduce cardiovascular and thromboembolic risk. 1

Understanding Erythrocytosis in TRT

• Testosterone therapy commonly causes increased red blood cell production (erythrocytosis), with hematocrit elevation being the most frequent adverse effect of TRT 2
• Injectable testosterone formulations carry a significantly higher risk of erythrocytosis (43.8%) compared to transdermal preparations (15.4%) 1
• Testosterone gel preparations show a dose-dependent relationship with erythrocytosis, with incidence rates increasing at higher doses 1

Monitoring Recommendations

• Hematocrit/hemoglobin levels should be measured at baseline before initiating testosterone therapy 1
• Follow-up monitoring should occur at 1-2 months, every 3-6 months during the first year, and annually thereafter if stable 1
• If baseline hematocrit exceeds 50%, testosterone therapy should be withheld until the cause is formally investigated 1

Intervention Thresholds and Options

• When hematocrit exceeds 54%, intervention is necessary to reduce cardiovascular and thromboembolic risk 1
• Intervention options include:
  • Therapeutic phlebotomy (blood donation) as a first-line intervention 1
  • Temporarily withholding testosterone therapy 3, 1
  • Reducing testosterone dosage 3, 1

Clinical Considerations for Blood Donation

• Blood donation alone may be insufficient to maintain hematocrit below 54% in TRT patients, with 44% of repeat donors showing persistently elevated levels despite donation 2
• Developing polycythemia (hematocrit ≥52%) while on TRT increases the risk of major adverse cardiovascular events and venous thromboembolism in the first year of therapy (OR 1.35,95% CI 1.13-1.61) 4
• TRT-associated erythrocytosis can lead to increased blood viscosity, which may impair microcirculation and oxygen delivery, particularly in elderly patients or those with vascular disease 3

Important Caveats

• Some clinicians have questioned the scientific basis for using exactly 54% as the cutoff, suggesting different thresholds may be more appropriate for specific patient groups 5
• Historical data suggests that hematocrit levels of 48% or greater may be associated with increased risk of cerebrovascular events in some patients 6
• Recent research indicates that RBCs from TRT donors have altered characteristics including decreased membrane deformability and increased susceptibility to oxidative stress, potentially affecting transfusion effectiveness 7
• Despite the increased risk of erythrocytosis with testosterone therapy, direct reports of testosterone-associated thromboembolic events are limited in major studies 1

Risk Factors Requiring Closer Monitoring

• Patients using injectable testosterone formulations (higher risk than transdermal) 3
• Patients with concurrent conditions that may independently increase hematocrit, such as chronic obstructive pulmonary disease 3
• Patients with existing cardiovascular disease or risk factors 4