What is the typical regimen for testosterone therapy in gender affirming care and how are testosterone levels monitored?

Testosterone Therapy in Gender Affirming Care: Regimens and Monitoring

Standard testosterone therapy for gender affirming care aims to achieve serum testosterone levels in the cisgender male reference range (300-1,000 ng/dL), with monitoring recommended every 3 months during the first year and then every 6-12 months thereafter. 1, 2

Standard Testosterone Regimens

Formulations and Dosing

• Injectable testosterone (most common):

  • Testosterone cypionate or enanthate: 50-400 mg every 2-4 weeks intramuscularly 3
  • Weekly subcutaneous injections: Starting at 50 mg/week, adjusted to 50-150 mg/week (median 75-80 mg) 4, 5
  • Subcutaneous administration is increasingly preferred due to:
    • Less pain compared to intramuscular injections 4
    • Ability for self-administration 4, 5
    • More stable testosterone levels between injections 5

• Other formulations:

  • Transdermal preparations (gels, patches)
  • Long-acting testosterone undecanoate (note: risk of pulmonary oil microembolism) 1

Dosing Approach

• Initial dosing typically starts at the lower end (e.g., 50 mg weekly for subcutaneous) 4, 6
• Dose is titrated based on:
  • Serum testosterone levels
  • Clinical response
  • Side effects

Monitoring Protocol

Laboratory Monitoring

• Testosterone levels:

  • Target: 300-1,000 ng/dL (mid-normal range 500-600 ng/dL optimal) 2
  • Timing:
    • For injections: Measure midway between injections 2
    • For transdermal: Can measure anytime (morning preferred) 2

• Frequency:

  • Initial follow-up: 1-2 months after starting 2
  • First year: Every 3 months 2, 7
  • After first year: Every 6-12 months if stable 2, 7

• Additional laboratory tests:

  • Hematocrit/hemoglobin (increases within 3 months) 1
  • Lipid profile (may see decreased HDL) 1
  • Liver function tests

Clinical Monitoring

• Physical changes to monitor:

  • Voice deepening (begins within 1-3 months) 8
  • Facial/body hair growth (begins within 1-3 months) 8
  • Menstrual cessation (typically within 2-3 months; 85% by 6 months) 6
  • Clitoral growth 1
  • Body composition changes (increased muscle mass, decreased fat) 1

• Side effects to monitor:

  • Polycythemia (if hematocrit rises above reference range, consider dose reduction or phlebotomy) 1, 2
  • Acne 1
  • Androgenic alopecia 1
  • Pelvic pain and genital dryness 1
  • Mood changes

Expected Timeline of Effects

• Early effects (1-3 months):

  • Cessation of menses (average 2.9 months) 6
  • Increased libido
  • Voice changes begin
  • Facial hair growth begins

• Intermediate effects (3-6 months):

  • Most patients achieve therapeutic testosterone levels
  • Significant voice deepening
  • Increased muscle mass
  • Body fat redistribution begins

• Long-term effects (1-5 years):

  • Maximum virilization typically achieved after 3-5 years of therapy 7
  • Continued facial and body hair development
  • Continued voice deepening

Important Clinical Considerations

• Dose-response relationship:

  • Higher initial doses lead to faster onset of physical changes 8
  • By 6 months, different dosing regimens achieve similar effects 8

• Irreversible changes:

  • Voice deepening and hair changes remain even if testosterone is discontinued 1

• Potential risks:

  • Cardiovascular: Possible increased risk of myocardial infarction 1
  • Hematologic: Polycythemia (testosterone increases hemoglobin to male range) 1
  • Metabolic: Reduced HDL cholesterol 1

• Subcutaneous vs. intramuscular administration:

  • Subcutaneous administration provides more stable testosterone levels between injections 5
  • Patients strongly prefer subcutaneous over intramuscular injections 4
  • Subcutaneous is effective across wide BMI ranges (19-49.9 kg/m²) 4

• Never discontinue testosterone abruptly without medical supervision 2

By following these guidelines for testosterone therapy and monitoring, healthcare providers can effectively support transgender individuals in their gender affirmation journey while minimizing potential risks.