What is the typical weekly intramuscular testosterone (enanthate or cypionate) dosing regimen for an otherwise healthy adult transgender male without contraindications such as active prostate cancer, severe cardiovascular disease, uncontrolled liver disease, or thromboembolic disorders?

Normal Weekly Testosterone Dosing for Transgender Males

For transgender males initiating gender-affirming hormone therapy, start with intramuscular testosterone enanthate or cypionate at 50–100 mg weekly (or 100–200 mg every 2 weeks), targeting serum testosterone levels in the physiologic male range of 300–1,000 ng/dL, with mid-normal values of 450–600 ng/dL preferred. 1, 2, 3

Initial Dosing Regimen

Injectable Testosterone (First-Line)

• Testosterone enanthate or cypionate: 50–100 mg weekly via intramuscular or subcutaneous injection is the most commonly recommended starting regimen 3, 4
• Alternative dosing: 100–200 mg every 2 weeks intramuscularly, though weekly administration provides more stable serum levels and reduces the problematic peaks and troughs seen with biweekly dosing 5, 3
• Subcutaneous administration is increasingly preferred over intramuscular injection due to ease of self-administration, less discomfort, and comparable efficacy 3
• Injection sites: anterolateral thigh (self-administered) or gluteal region (administered by another person) 3

Alternative Formulations

• Transdermal testosterone gel 1.62%: 40.5 mg daily is an alternative first-line option, offering more stable day-to-day testosterone levels compared to injections 1, 3
• Testosterone undecanoate: 750 mg initially, repeat at 4 weeks, then every 10 weeks (gluteal IM only), providing fewer yearly injections with less fluctuation 3

Target Testosterone Levels

• Aim for serum testosterone concentrations in the typical physiological range for cisgender men: 300–1,000 ng/dL 1
• Target mid-normal values of 450–600 ng/dL when measured midway between injections (days 5–7 for weekly dosing) 2, 3
• Peak serum levels occur 2–5 days after injection, with return to baseline by days 10–14 2, 5

Monitoring Schedule

Initial Phase (First Year)

• Measure testosterone levels at 2–3 months after treatment initiation or any dose change, timing the blood draw midway between injections 2, 3
• Repeat monitoring every 3–6 months during the first year, assessing testosterone levels, hematocrit, and clinical response 2
• Once stable levels are achieved, monitor every 6–12 months 2, 3

Key Safety Parameters

• Hematocrit monitoring is mandatory at each visit; withhold treatment if hematocrit exceeds 54% and consider phlebotomy in high-risk cases 2, 3
• Injectable testosterone carries a 43.8% risk of erythrocytosis compared to 15.4% with transdermal preparations 3
• Monitor for polycythemia, as 25.6% of transgender men on testosterone develop hematocrit >50% 6

Expected Physical Changes

Timeline of Masculinizing Effects

• Menstrual cessation: typically within 3–6 months, with cumulative cessation rates not significantly different between low-dose (≤62.5 mg/week) and high-dose (>62.5 mg/week) groups by 12 months 7
• Voice deepening, increased facial/body hair, clitoral enlargement: begin within several months, with facial hair and alopecia continuing to develop after 1 year 8
• Body composition changes: decreased body fat percentage and increased lean body mass occur during the first year, with the high-dose group showing greater lean mass gains initially 7
• Maximum clitoral length (mean 4.6 cm): achieved by 1 year of therapy 4

Metabolic and Laboratory Changes

• Hematocrit increases by approximately 12% (from ~40% to ~49%) 6
• Significant increases in creatinine and uric acid levels 6
• Decreased fasting plasma glucose 6
• Possible increases in LDL cholesterol and decreases in HDL cholesterol 1, 6
• Mild elevation of cholesterol and triglycerides 4

Dose Adjustment Algorithm

When to Increase Dose

• If clinical response is suboptimal (persistent gender dysphoria, inadequate masculinization) and testosterone levels are low-normal or below target, increase the dose 2
• Higher testosterone doses (>62.5 mg/week) lead to earlier increases in muscle mass, though low-dose administration is sufficient for adequate muscular development long-term 7

When to Decrease Dose

• If testosterone levels exceed 1,000 ng/dL (supraphysiologic), reduce dose by approximately 50% to minimize erythrocytosis risk 3
• If hematocrit rises above 52–54%, reduce testosterone dose by 25–50% or switch from injectable to transdermal formulation 2

Formulation Selection Considerations

Injectable vs. Transdermal

• Injectable testosterone advantages: relatively inexpensive (annual cost ~$156 vs. ~$2,135 for transdermal), flexible dosing intervals 3
• Injectable testosterone disadvantages: requires intramuscular injection, fluctuating serum testosterone levels, higher erythrocytosis risk (43.8% vs. 15.4%) 3
• Transdermal gel advantages: easy application, good skin tolerability, more stable day-to-day levels, lower erythrocytosis risk 3
• Transdermal gel disadvantages: potential for transfer to partners or children, more expensive 3

Weekly vs. Biweekly Dosing

• Weekly dosing (50–100 mg) is increasingly favored because it reduces problematic peaks and troughs, providing more stable testosterone levels 5, 3
• Biweekly dosing (100–200 mg) causes greater fluctuation, with patients spending significant time in both supratherapeutic and subtherapeutic ranges, potentially contributing to increased cardiovascular risk 5

Common Pitfalls to Avoid

• Do not dose based on peak levels (days 2–5 post-injection); patients may appear to have adequate testosterone when measured shortly after injection but will spend most of the dosing interval in subtherapeutic ranges 5
• Do not measure testosterone outside the 8–10 AM window for baseline assessments, as diurnal variation causes lower values later in the day 2
• Do not ignore mild erythrocytosis (hematocrit 50–52%); even modest elevations increase blood viscosity and thrombotic risk 2
• Do not continue full-dose testosterone when hematocrit exceeds 54%; this is an absolute indication to withhold therapy 2
• Do not assume all gel formulations are interchangeable; the 1.62% formulation delivers more testosterone per gram than the 1% formulation, requiring different dosing 3

Additional Benefits and Risks

Psychological Benefits

• Reductions in gender dysphoria, perceived stress, anxiety, and depression 8
• Increased sexual desire 8

Cancer Risk

• Reduced risk of breast cancer with testosterone therapy (with or without mastectomy) 8

Cardiovascular Considerations

• Possible increase in systolic blood pressure 8
• Minimal impact on cardiovascular outcomes in transgender men, with contradictory data showing no significant difference in cardiovascular mortality relative to the general population 1

Other Side Effects

• Acne and alopecia (male-pattern baldness) 8
• Reduced HDL cholesterol and increased triglycerides 8

Long-Term Safety

• Long-term gender-affirming hormone therapy for transgender men is safe and effective, with no dose-dependent side effects such as polycythemia or dyslipidemia observed in extended follow-up 7
• Low-dose testosterone administration (≤62.5 mg/week) is sufficient to increase lean body mass and achieve adequate muscular development in transgender men 7
• No thromboembolism, cancer, stroke, or coronary artery disease occurred in short-term follow-up studies 6