What is the target testosterone level for transgender females?

Target Testosterone Levels for Transgender Females

The target testosterone level for transgender females should be in the cisgender female reference range, with a goal of <50 ng/dL for optimal feminization and reduced health risks. 1

Hormone Therapy Goals and Targets

• Feminizing hormone therapy aims to suppress endogenous testosterone production while providing estradiol to induce feminine secondary sex characteristics
• Specific testosterone targets:
  • Below 50 ng/dL is considered optimal 2
  • Within the typical cisgender female reference range 1
  • Suppression should be monitored regularly, as up to 25% of transgender women may have nonsuppressed testosterone levels 3

Medication Regimens to Achieve Target Levels

Feminizing hormone therapy typically consists of:

1. Estradiol therapy - Available in multiple formulations:

   • Transdermal (patches): More effective at testosterone suppression with lower overall estradiol doses 2
   • Oral/sublingual: May require higher doses for adequate suppression 2

2. Anti-androgen medications (for those who have not had orchidectomy):

   • Spironolactone: Commonly used in US, peripheral androgen receptor antagonist 1
   • Cyproterone acetate: Effective but has potential health risks 4
   • GnRH analogues: Highly effective but more expensive 4
   • Bicalutamide or finasteride: Alternative options 1

Monitoring Protocol

• Testosterone levels should be checked:

  • Every 3 months during the first year of therapy
  • Every 6-12 months thereafter if stable 5
  • Midway between injections for injectable formulations
  • Any time (but consistently in morning) for transdermal preparations 5

• Additional monitoring:

  • Estradiol levels
  • Comprehensive metabolic panel
  • Lipid profile
  • Complete blood count

Clinical Considerations and Risks

• Cardiovascular risk: Transgender women have elevated risk of venous thromboembolism (VTE) and potentially increased cardiovascular mortality (2-4 fold) compared to cisgender women 1

  • Transdermal estradiol may carry lower VTE risk than oral formulations
  • Ethinyl estradiol should be avoided due to higher VTE risk 1

• Body composition changes: Expect decreases in:

  • Muscle volume (5%)
  • Quadriceps cross-sectional area (4%)
  • Lean body mass (3.0-5.5%)
  • Increases in total body fat 1

• Breast development: Important for many transgender women

  • May plateau after 6 months or continue for up to 3 years 1
  • Progestins are not routinely recommended by guidelines due to potential risks 1

Approach to Nonsuppressed Testosterone

If testosterone levels remain above target despite therapy:

1. Verify medication adherence
2. Consider increasing anti-androgen dose
3. Consider changing anti-androgen class
4. Evaluate for underlying medical conditions affecting hormone metabolism
5. Consider surgical options (orchiectomy) if persistent nonsuppression affects quality of life 3

Common Pitfalls to Avoid

• Inadequate monitoring: Failure to check testosterone levels regularly may miss nonsuppression
• Suboptimal anti-androgen therapy: Some patients require higher doses or different agents
• Overreliance on estradiol alone: Most transgender women require both estradiol and anti-androgens to achieve female-range testosterone levels 6
• Ignoring cardiovascular risk factors: Additional risk reduction strategies are important for those with existing risk factors

Achieving and maintaining appropriate testosterone suppression is critical for both the physical feminization desired by transgender women and for minimizing health risks associated with cross-sex hormone therapy.