What is the ideal serum testosterone level for a female-to-male transgender patient undergoing testosterone therapy?

Ideal Testosterone Level for Female-to-Male Transition

Target Serum Testosterone Range

Maintain serum total testosterone between 300–1,000 ng/dL (the typical cisgender male physiological range), specifically targeting the mid-normal range of 450–600 ng/dL to optimize masculinization while minimizing adverse effects. 1

This target is endorsed across multiple guidelines and represents the standard of care for masculinizing hormone therapy. 2, 3

Rationale for the Mid-Normal Target

• The 300–1,000 ng/dL range reflects physiological testosterone concentrations in cisgender men and serves as the therapeutic goal for gender-affirming hormone therapy. 2, 1

• Targeting 450–600 ng/dL (mid-normal) balances efficacy with safety, providing adequate virilization while reducing risks of erythrocytosis and cardiovascular complications. 1

• Levels below 300 ng/dL may compromise bone mineral density and limit desired masculinization effects, while levels consistently above 1,000 ng/dL increase adverse effects without additional therapeutic benefit. 1

Monitoring Protocol and Timing

Initial Phase

• Measure testosterone levels 2–3 months after starting therapy or any dose adjustment. 1, 3

• For injectable formulations (testosterone cypionate or enanthate), draw trough levels immediately before the next scheduled injection to capture representative steady-state concentrations. 1

• Continue monitoring every 3–6 months during the first year, then reduce to every 6–12 months once stable therapeutic levels are achieved. 1, 3

Common Pitfall to Avoid

• Do not measure peak levels (2–5 days post-injection), as these can be supraphysiologic and misleadingly suggest the need for dose reduction when trough levels may actually be subtherapeutic. 1

Expected Physical Changes by Testosterone Level

When testosterone is maintained in the target range, the following timeline applies:

• Within 3 months: Cessation of menses, increased libido, early clitoral growth, and hemoglobin rising to male reference range. 2, 1

• 3–6 months: Voice deepening begins, facial and body hair growth starts, noticeable increase in muscle mass and reduction in fat mass. 1

• 1–2 years: Continued voice deepening, progressive facial hair development, body composition changes plateau. 1

• 3–5 years: Maximal virilization achieved, though facial hair and androgenic alopecia may continue to progress. 1, 4, 3

Critical Safety Monitoring

Erythrocytosis Risk

• Polycythemia occurs in approximately 44% of transgender men using injectable testosterone, making hematocrit monitoring essential. 2, 1

• Monitor hemoglobin and hematocrit at baseline, at 3 months, then every 6–12 months. 1

• If hematocrit exceeds 54% or rises above the male reference range, reduce dose, switch to transdermal formulation, or perform therapeutic phlebotomy. 1

• Transdermal testosterone gel carries lower erythrocytosis risk (approximately 15%) compared to injectable formulations and should be considered for patients who develop elevated hematocrit. 1

Cardiovascular and Metabolic Monitoring

• Testosterone may increase blood pressure, triglycerides, and LDL cholesterol while decreasing HDL cholesterol. 2, 1

• Regular lipid panels and blood pressure checks are warranted, particularly in patients with pre-existing cardiovascular risk factors. 1

• Large cohort studies have not demonstrated significantly increased cardiovascular mortality in transgender men on testosterone therapy. 1

Formulation-Specific Considerations

Injectable Testosterone (Most Common)

• Testosterone cypionate or enanthate: 100–200 mg intramuscularly or subcutaneously every 2 weeks, or 50–100 mg weekly. 1

• Weekly dosing provides more stable serum levels and reduces erythrocytosis risk compared to biweekly administration. 1

Transdermal Testosterone Gel

• Starting dose: 40.5 mg (1.62% gel) applied daily to shoulders, upper arms, or abdomen. 1

• Offers stable day-to-day levels and lower erythrocytosis risk, making it preferable for patients with elevated hematocrit or cardiovascular concerns. 1

• Annual cost is significantly higher ($2,135 for transdermal vs. $156 for injectable). 1

Quality-of-Life Outcomes

• Gender-affirming testosterone therapy is medically necessary for many transgender individuals and is associated with significant improvements in quality of life, reduced gender dysphoria, and lower rates of anxiety and depression. 1, 4

• Most desired physical effects appear within 6–12 months, while maximal virilization typically requires 3–5 years of consistent therapy at therapeutic testosterone levels. 1, 4, 3

Algorithm for Dose Adjustment

If testosterone level is < 300 ng/dL (measured at trough):

• Increase dose by 25–50% and recheck in 2–3 months. 1

If testosterone level is 300–450 ng/dL:

• Consider modest dose increase if masculinization is suboptimal; otherwise maintain current dose. 1

If testosterone level is 450–600 ng/dL:

• Ideal range—maintain current dose. 1

If testosterone level is 600–1,000 ng/dL:

• Acceptable if no adverse effects; monitor hematocrit closely and consider dose reduction if erythrocytosis develops. 1

If testosterone level is > 1,000 ng/dL:

• Reduce dose by approximately 50% immediately to minimize risk of erythrocytosis and cardiovascular complications. 1