What is the recommended approach to testosterone therapy for a female-to-male (FTM) transition?

Testosterone Therapy for Female-to-Male Transition

Recommended Testosterone Regimen

Initiate testosterone therapy using intramuscular or subcutaneous testosterone cypionate or enanthate, targeting serum testosterone levels of 300-1,000 ng/dL, with the mid-normal range (approximately 500-700 ng/dL) being optimal for safety and efficacy. 1

Dosing and Administration Options

Intramuscular/Subcutaneous Injectable Testosterone (Preferred)

• Testosterone cypionate or enanthate is the most common and effective modality for FTM transition 1, 2
• Average weekly dose is approximately 46.4 mg, though this requires individualized titration 3
• Subcutaneous administration is equally effective as intramuscular and offers significant advantages: it is relatively painless, easy to self-inject, and maintains stable testosterone levels between injections 2, 3
• Subcutaneous delivery achieves therapeutic levels with 91.4% of patients reaching normal male range within 6 months 3
• Serum levels remain stable throughout the dosing interval (mean 627 ± 206 ng/dL total testosterone) 2

Transdermal Testosterone (Alternative)

• Testosterone gel 1.62% can be used, applied to clean, dry, intact skin of upper arms and shoulders only 4
• Starting dose typically 20.25-40.5 mg daily, titrated based on serum levels 4
• Critical safety concern: Must cover application sites with clothing after drying to prevent transfer to others, particularly women and children 4
• Consider switching from injectable to transdermal if erythrocytosis develops 1

Pre-Treatment Screening Requirements

Before initiating testosterone, screen for liver abnormalities and obtain baseline polycythemia assessment 5

Baseline laboratory evaluation should include:

• Complete blood count (hemoglobin/hematocrit) 1, 6
• Liver function tests 5, 6
• Lipid profile 1, 6
• Baseline testosterone levels 6
• Blood pressure measurement 1

Target Hormone Levels and Monitoring Schedule

Maintain trough testosterone levels between 300-1,000 ng/dL, targeting the mid-normal range 1

Monitoring Timeline

• First follow-up: 14 and 28 days after initiation to assess testosterone levels and adjust dosing 4
• First year: Every 3 months for hormone levels, CBC, liver function, and lipid profile 6, 7
• After first year: Every 6-12 months if stable 6, 7

Laboratory Parameters to Monitor

• Serum testosterone (trough levels before next dose) 1, 4
• Hemoglobin/hematocrit (will increase to male reference range within 3 months) 1, 6
• Blood pressure (testosterone may increase BP) 1, 6
• Lipid profile (may increase triglycerides and LDL, decrease HDL) 1, 6, 8
• Liver enzymes (testosterone may cause transient elevations) 5

Expected Physical Changes and Timeline

Most masculinizing effects begin within several months, with maximum virilization achieved after 3-5 years of regular use 8, 7

Changes Within 3-6 Months:

• Menstrual cessation (85% achieve this within 6 months, average 2.9 months) 1, 3
• Deepening of voice due to thickened vocal cords 1
• Increased muscle mass and decreased fat mass 1, 8
• Clitoral growth 1
• Increased libido 1, 8
• Hemoglobin increase to male reference range 1

Ongoing Changes (Beyond 1 Year):

• Facial and body hair growth (continues to develop after 1 year) 1, 8
• Androgenic alopecia (male pattern baldness) may develop 1, 8

Psychological Benefits:

• Reductions in gender dysphoria, perceived stress, anxiety, and depression 8
• Improved quality of life 9, 8

Critical Adverse Effects and Management

Erythrocytosis/Polycythemia (Most Important Complication)

This is particularly common with injectable formulations and requires vigilant monitoring 1, 6

Management approach:

• If hematocrit rises above normal male reference range, consider temporarily withholding therapy, reducing dose, or performing phlebotomy 5
• Switch to transdermal route if erythrocytosis develops, as this reduces risk 1, 6
• Recommend smoking cessation and weight loss if BMI is elevated 6

Cardiovascular Considerations

• Monitor blood pressure regularly (testosterone may increase BP) 1, 6
• Check lipid profiles: expect increased triglycerides and LDL cholesterol, decreased HDL 1, 6, 8
• Contradictory data exists regarding actual cardiovascular outcomes: some studies show no significant difference in cardiovascular mortality compared to general population, despite changes in risk factors 6
• Possible increased risk of myocardial infarction, though evidence is mixed 1, 8

Dermatologic Effects

• Acne is common 1, 8
• Androgenic alopecia (male pattern baldness) 1, 8

Gynecological Effects

• Pelvic pain and genital dryness may occur 1

Hepatic Effects

• Testosterone may cause transient, self-limited elevations in liver enzymes 5
• Patients with advanced liver disease can receive testosterone therapy, though closer monitoring is warranted 5

Critical Pitfalls to Avoid

Avoid supraphysiologic dosing (levels >1,000 ng/dL), which increases risk of adverse effects without additional benefit 1

Common Errors:

• Failing to screen for liver disease and polycythemia before initiation 5
• Not monitoring hematocrit regularly, missing dangerous erythrocytosis 1, 6
• Using testosterone gel without proper counseling about transfer risk to others 4
• Applying testosterone gel to incorrect body sites (abdomen, genitals, chest) 4
• Not covering gel application sites with clothing 4
• Inadequate follow-up during first year when dose adjustments are most needed 4, 7

Safety Precautions for Transdermal Formulations:

• Children and women must avoid contact with unwashed or unclothed application sites 4
• Patients must wash hands thoroughly with soap and water immediately after application 4
• Cover application sites with clothing (e.g., t-shirt) after gel dries 4
• Avoid swimming or showering for minimum 2 hours after application 4
• Wash application sites thoroughly with soap and water before anticipated skin-to-skin contact 4

Special Populations

Patients with Liver Disease

• Testosterone therapy can be used safely in patients with chronic liver disease, including those with decompensated disease 5
• Benefits include increases in muscle and bone mass, with trend toward lowering mortality 5
• Female-to-male transgender patients should be screened for liver abnormalities before initiation of high-dose androgen therapy 5

Laboratory Interpretation

• After more than 1 year of hormone therapy, interpret laboratory values based on affirmed gender (male reference ranges) 6
• Consider using cystatin C rather than creatinine for kidney function evaluation, as it is less dependent on muscle mass 6