What is the treatment approach for polycythemia in a trans masculine patient on testosterone (hormone) therapy?

Management of Polycythemia in Transgender Masculine Patients on Testosterone Therapy

For transgender masculine patients with polycythemia due to testosterone therapy, the most effective approach is to reduce or temporarily discontinue testosterone therapy, switch to transdermal formulations, address modifiable risk factors, and consider therapeutic phlebotomy when hematocrit exceeds 54%. 1, 2

Monitoring and Diagnosis

• Prior to initiating testosterone therapy, baseline hemoglobin/hematocrit levels should be measured to identify pre-existing abnormalities 1
• If baseline hematocrit exceeds 50%, consider investigating underlying causes before starting testosterone therapy 1
• Regular monitoring of hemoglobin/hematocrit is essential, particularly during the first year of therapy when the largest increases typically occur 3
• Continue monitoring throughout treatment, as the probability of developing erythrocytosis increases with duration of therapy (10% after 1 year, 38% after 10 years) 3

Risk Factors for Polycythemia in Transgender Masculine Patients

• Injectable testosterone formulations carry higher risk than transdermal preparations 1, 4, 3
  • Intramuscular testosterone enantate: 23.3% incidence of polycythemia
  • Intramuscular testosterone undecanoate: 15% incidence
  • Transdermal testosterone: significantly lower risk (0% in some studies)
• Additional risk factors include:
  • Tobacco use (OR 2.2) 3
  • Older age at initiation of hormone therapy (OR 5.9) 3
  • Higher BMI (OR 3.7) 3
  • Pulmonary conditions (OR 2.5) 3
  • Previous oophorectomy (novel finding requiring further research) 5
  • Higher testosterone dosage 5

Management Algorithm

1. For Mild Polycythemia (Hematocrit 50-52%):

• Continue monitoring more frequently (every 3 months) 1
• Address modifiable risk factors:
  • Smoking cessation 3
  • Weight loss if BMI is elevated 3
  • Consider switching from injectable to transdermal testosterone 1, 3

2. For Moderate Polycythemia (Hematocrit 52-54%):

• Consider dose reduction of testosterone therapy 1, 2
• Switch from injectable to transdermal formulation if not already done 1, 4, 3
• Address all modifiable risk factors aggressively 3
• Consider blood donation if otherwise eligible 6

3. For Severe Polycythemia (Hematocrit >54%):

• Temporarily discontinue testosterone therapy until hematocrit decreases to an acceptable level 2
• Implement therapeutic phlebotomy 1
• After hematocrit normalizes, restart at lower dose and/or switch to transdermal formulation 1, 3
• Continue close monitoring after restarting therapy 1

Clinical Implications and Concerns

• Polycythemia is common in transgender masculine patients on testosterone therapy, affecting approximately 11-22% of patients 5, 3
• Elevated hematocrit increases blood viscosity, which may aggravate vascular disease in coronary, cerebrovascular, or peripheral circulation 1
• Recent evidence shows increased risk of major adverse cardiovascular events (MACE) and venous thromboembolism (VTE) in the first year of therapy for patients who develop polycythemia (OR 1.35) 7
• Blood donation alone may be insufficient to maintain hematocrit below target levels in patients continuing testosterone therapy 6

Important Caveats

• Therapeutic decisions should balance gender-affirming care needs with cardiovascular risk management 1
• Simply discontinuing testosterone therapy without addressing gender dysphoria can have significant negative mental health impacts 1
• When reducing testosterone dose or changing formulation, continue to monitor both hematocrit and testosterone levels to ensure therapeutic gender-affirming effects are maintained 1
• Patients with additional risk factors for polycythemia (smoking, obesity, pulmonary conditions) require more vigilant monitoring 3