Goal Testosterone for Hormone Replacement Therapy in Transgender Men
Target Testosterone Range
For transgender men receiving testosterone hormone therapy, target serum total testosterone concentrations should be maintained between 300–1,000 ng/dL (the typical cisgender male physiological range), with most guidelines recommending aiming for the mid-normal range of 450–600 ng/dL to optimize efficacy while minimizing adverse effects. 1, 2, 3, 4
Rationale for Target Range
The 300–1,000 ng/dL range represents the physiological testosterone concentrations observed in cisgender men and is the standard target for masculinizing hormone therapy in transgender men 1, 2, 3
Targeting the mid-normal range (450–600 ng/dL) is preferred because it balances optimal masculinization effects with safety, particularly reducing the risk of erythrocytosis and cardiovascular complications 1, 2, 3
Inadequate testosterone dosing (levels consistently below 300 ng/dL) can negatively impact bone density and fail to achieve desired masculinization, while supraphysiologic levels (>1,000 ng/dL) increase adverse effects without additional clinical benefit 1, 3
Timing of Testosterone Measurement
Trough levels should be measured for injectable testosterone formulations (testosterone cypionate or enanthate), drawn immediately before the next scheduled injection 1, 2, 4
For transdermal testosterone gel, levels can be measured at any time after 2–3 months of stable therapy, though some protocols recommend checking both peak (+2 hours post-application) and trough (+23 hours) levels to ensure adequate coverage throughout the day 5
Initial monitoring should occur 2–3 months after treatment initiation or any dose change, then every 3–6 months during the first year, and every 6–12 months once stable levels are achieved 1, 2, 4
Expected Physical Changes and Timeline
Within 3 months: Menstrual cessation, increased libido, clitoral growth begins, hemoglobin rises to male reference range 1, 3
3–6 months: Voice deepening begins, facial and body hair growth starts, increased muscle mass and decreased fat mass become noticeable 1, 3, 6
1–2 years: Continued voice deepening, progressive facial hair growth, body composition changes plateau 1, 6
3–5 years: Maximum virilization effects typically achieved, though facial hair and androgenic alopecia may continue to develop beyond this timeframe 1, 6, 4
Critical Monitoring Parameters
Hematologic Monitoring
Erythrocytosis/polycythemia is the most common adverse effect, occurring in approximately 44% of transgender men on injectable testosterone 1, 3
Monitor hemoglobin and hematocrit at baseline, 3 months, then every 6–12 months 1, 3, 4
If hematocrit exceeds 54% or rises above the male reference range, consider dose reduction, switching from injectable to transdermal formulations, or therapeutic phlebotomy 1, 3
Transdermal testosterone gel carries significantly lower erythrocytosis risk (approximately 15%) compared to injectable formulations (44%) 1, 3
Cardiovascular and Metabolic Monitoring
Testosterone may increase blood pressure, triglycerides, and LDL cholesterol while decreasing HDL cholesterol 1, 3, 6
Monitor lipid profiles and blood pressure regularly, particularly in patients with pre-existing cardiovascular risk factors 1, 3
Despite unfavorable lipid changes, large studies have not demonstrated significantly increased cardiovascular mortality in transgender men on testosterone therapy 1
Other Monitoring
Liver function tests at baseline and periodically, though clinically significant hepatotoxicity is rare with injectable or transdermal testosterone 3
Screen for androgenic alopecia, acne, and gynecological symptoms (pelvic pain, vaginal dryness) 1, 3, 6
Formulation Selection and Dosing
Injectable Testosterone (Most Common)
Testosterone cypionate or enanthate: 100–200 mg intramuscularly or subcutaneously every 2 weeks, or 50–100 mg weekly 1, 7, 3, 4
Weekly dosing provides more stable testosterone levels and reduces the risk of erythrocytosis compared to biweekly administration 1, 7
Injectable formulations are significantly more cost-effective ($156 annually) compared to transdermal options ($2,135 annually) 7
Transdermal Testosterone
Testosterone gel 1.62%: Starting dose 40.5 mg daily, applied to shoulders, upper arms, or abdomen 1, 7, 3
Transdermal formulations offer more stable day-to-day testosterone levels and lower erythrocytosis risk, making them preferred for patients with elevated hematocrit or cardiovascular risk factors 1, 7, 3
Main disadvantages include higher cost and potential for transfer to partners or children through skin contact 7
Testosterone Undecanoate (Long-Acting)
- Avoid in most cases due to concerns for pulmonary oil microembolism and anaphylaxis; subject to risk evaluation and mitigation strategies 1, 3
Common Pitfalls to Avoid
Do not use supraphysiologic dosing (testosterone levels consistently >1,000 ng/dL), as this increases adverse effects—particularly erythrocytosis—without additional masculinization benefit 1, 3
Do not measure testosterone levels at peak times (2–5 days post-injection for injectable formulations), as this will show supraphysiologic levels that do not reflect average exposure and may lead to inappropriate dose reduction 1, 2
Do not ignore erythrocytosis: Even mild elevations in hematocrit (50–52%) warrant closer monitoring and potential dose adjustment, particularly in patients with cardiovascular risk factors 1, 3
Do not assume all patients will achieve target levels on standard dosing: Approximately 25–30% of transgender men may require dose adjustments to reach therapeutic testosterone concentrations 8
Do not overlook bone health: Inadequate testosterone dosing can negatively impact bone mineral density, making appropriate dosing and monitoring essential 1, 3
Quality of Life and Mental Health Benefits
Gender-affirming hormone therapy with testosterone is medically necessary for many transgender individuals, with strong evidence showing improvements in quality of life, reductions in gender dysphoria, and decreased anxiety and depression 1, 3, 6
Most desired physical effects develop within 6–12 months, though maximal virilization typically requires 3–5 years of consistent therapy 1, 6, 4