What is the typical hormone therapy regimen for female to male transition?

Female to Male Hormone Therapy

The typical hormone therapy regimen for female-to-male transition consists of testosterone therapy with standard dosing aimed at achieving serum testosterone concentrations of 300-1,000 ng/dL (the cisgender male physiological range), most commonly administered via intramuscular or subcutaneous injection of testosterone cypionate or enanthate. 1, 2, 3

Standard Testosterone Regimen

Initial Dosing

• Start with testosterone cypionate or enanthate 50-100 mg intramuscularly or subcutaneously every 1-2 weeks 4, 5, 6
• Injectable testosterone esters (cypionate or enanthate) are the most commonly used formulations and are typically administered subcutaneously, which is equally effective as intramuscular administration but better tolerated 6
• For FDA-approved intramuscular formulations, the dosage range is 50-400 mg every 2-4 weeks, though weekly dosing is more common in transgender care 5

Alternative Formulations

• Topical testosterone gel 1.62% can be used, starting at 20.25-40.5 mg daily applied to upper arms and shoulders, with dose adjustments based on serum levels 4
• Transdermal formulations may reduce the risk of erythrocytosis compared to injectable forms 2, 3
• Testosterone undecanoate (long-acting injectable) should be used with caution due to risk of pulmonary oil microembolism and anaphylaxis 3

Target Hormone Levels and Monitoring

Testosterone Targets

• Maintain trough testosterone levels between 300-1,000 ng/dL (measured immediately before the next scheduled dose) 2, 3
• The Endocrine Society recommends targeting the mid-normal range to optimize safety and efficacy 3
• Hemoglobin will increase to the male reference range within 3 months of starting therapy 1

Monitoring Schedule

• Baseline assessment: Complete blood count, liver function, lipid profile, glucose, and baseline hormone levels 2
• Check testosterone levels at 1-3 months after initiation or dose adjustment 7, 4
• Continue monitoring every 3-6 months during the first year, then annually 7
• For topical gel formulations, assess serum testosterone at approximately 14 days and 28 days after starting treatment 4

Expected Physical Changes

Irreversible Changes

• Deepening of voice due to thickened vocal cords 1
• Facial and body hair growth 1
• These changes persist even if testosterone therapy is discontinued 1

Reversible Changes

• Menstrual suppression (typically achieved in most patients) 1
• Clitoral growth 1
• Increased muscle mass and decreased fat mass (thigh muscle volume increases by approximately 15%, quadriceps cross-sectional area increases by 6%) 1
• Increased libido 1

Timeline of Effects

• Early onset of physical changes (voice deepening, facial hair, menstrual cessation) is dose-dependent in the first month 8
• By 6 months, most patients achieve treatment responses regardless of initial dose 8

Critical Monitoring Parameters

Hematological Surveillance

• Monitor for erythrocytosis/polycythemia (hematocrit >50%), which is particularly common with injectable formulations (occurring in up to 66.7% of patients on injectable testosterone) 2, 3, 9
• If erythrocytosis develops: recommend smoking cessation, weight loss if BMI is elevated, and consider switching to transdermal route 2, 3

Cardiovascular Monitoring

• Monitor blood pressure, as testosterone may increase blood pressure 2, 3
• Check lipid profiles regularly: testosterone may increase triglycerides and LDL cholesterol while decreasing HDL 2, 3
• Despite changes in cardiovascular risk factors, studies show contradictory data regarding actual cardiovascular outcomes, with no significant difference in cardiovascular mortality compared to the general population 2

Laboratory Value Interpretation

• After more than 1 year on hormone therapy, interpret laboratory values based on the affirmed gender (male reference ranges) 2
• Consider using cystatin C rather than creatinine for kidney function evaluation, as it is less dependent on muscle mass 2

Common Pitfalls and Adverse Effects

Dose-Related Issues

• Avoid supraphysiologic dosing (testosterone levels >1,000 ng/dL), which increases risk of adverse effects without additional benefit 3
• Injectable formulations cause more significant erythrocytosis than topical formulations 9

Other Adverse Effects

• Androgenic alopecia and acne are common 1
• Gynecological effects including pelvic pain and genital dryness may occur 1
• Reduced HDL cholesterol 1
• Potential increased risk of myocardial infarction, though evidence is mixed 1

Practical Administration Considerations

Injectable Testosterone

• Subcutaneous administration is equally effective as intramuscular and is preferred by patients (all 22 patients who switched from IM to SC in one study preferred SC) 6
• Effective across a wide range of body mass index (19.0-49.9 kg/m²) 6
• Minor and transient local reactions occur in approximately 14% of patients 6

Topical Testosterone Gel

• Must be applied to clean, dry, intact skin of upper arms and shoulders only 4
• Avoid swimming or showering for minimum of 2 hours after application 4
• Cover application site with clothing after gel dries to prevent transfer to others 4
• Children and women must avoid contact with unwashed or unclothed application sites 4