What are the typical doses for Testosterone Replacement Therapy (TRT)?

Testosterone Replacement Therapy Dosing

For testosterone replacement therapy, start with testosterone enanthate or cypionate 100-200 mg intramuscularly every 2 weeks, or preferably 50-100 mg weekly for more stable levels, with transdermal gels (50-100 mg daily) as an alternative first-line option. 1

Injectable Testosterone Formulations

Short-Acting Esters (Enanthate/Cypionate)

• Testosterone enanthate or cypionate should be initiated at 100-200 mg every 2 weeks or 50-100 mg weekly via intramuscular injection. 1
• Weekly dosing of 50-100 mg provides significantly more stable testosterone levels compared to biweekly administration, which is clinically important for reducing adverse effects. 1
• These injections can be self-administered in the anterolateral thigh or given by another person in the gluteal region. 1
• The 200 mg every 2 weeks regimen has been validated in multiple studies as effective for suppressing LH to normal levels and maintaining testosterone within the physiological range. 2

Long-Acting Ester (Undecanoate)

• Testosterone undecanoate requires 750 mg initially, followed by 750 mg at 4 weeks, then 750 mg every 10 weeks thereafter. 1
• This formulation must be administered as a gluteal intramuscular injection only (not self-administered). 1
• Undecanoate provides the advantage of fewer yearly injections with less fluctuation in testosterone levels compared to shorter-acting esters. 1, 3

Subcutaneous Alternative

• Subcutaneous testosterone cypionate or enanthate at 50-150 mg weekly (median 75-80 mg) is an effective alternative to intramuscular injection, achieving normal male testosterone levels across a wide BMI range. 4
• Patients demonstrate marked preference for subcutaneous over intramuscular administration when given the choice. 4

Transdermal Formulations

• AndroGel 1% should be applied at 50-100 mg daily to the shoulders and upper arms. 1, 5
• Testosterone gel 1.62% should be started at 40.5 mg daily (2 pump actuations), with dose adjustments ranging from 20.25 mg to 81 mg based on serum levels. 6
• Testosterone patches (Androderm) should be applied at 2-6 mg per 24 hours. 1
• Transdermal preparations produce more physiological circadian testosterone variations compared to injections. 7

Monitoring and Dose Titration Algorithm

Initial Monitoring

• Measure testosterone levels 2-3 months after treatment initiation or any dose change. 1, 8
• For injectable formulations, draw levels midway between injections, targeting mid-normal values (450-600 ng/dL). 1, 8
• For transdermal preparations, levels can be measured at any time, though peak values occur 6-8 hours after application. 8

Dose Adjustment Criteria

• If pre-dose morning testosterone is >750 ng/dL, decrease the dose. 6
• If testosterone is 350-750 ng/dL, continue current dose. 6
• If testosterone is <350 ng/dL, increase the dose. 6

Long-Term Monitoring

• Once stable levels are achieved, monitor every 6-12 months including testosterone levels, hematocrit/hemoglobin, PSA with prostate examination, and lipid panel. 1, 8

Safety Considerations and Formulation Selection

Cardiovascular and Hematologic Risks

• Injectable testosterone carries greater cardiovascular risk compared to transdermal preparations, possibly due to fluctuating testosterone levels. 1, 8
• Erythrocytosis occurs significantly more frequently with injectable formulations (43.8% of patients) compared to transdermal therapy (15.4% of patients). 1, 7
• Supraphysiological testosterone levels occur for several days after intramuscular injections, which may contribute to excessive erythropoiesis stimulation. 7

Formulation Selection Framework

• The Endocrine Society recommends transdermal testosterone gels as first-line therapy due to stable physiologic testosterone levels and patient convenience, with intramuscular injections reserved for those with cost constraints or adherence issues. 8
• Injectable advantages include lower cost and flexible dosing intervals, but require intramuscular injection and produce fluctuating serum levels. 1
• Transdermal gel advantages include easy application and good skin tolerability, but carry risk of transfer to partners or children and higher cost. 1

Critical Precautions

Secondary Exposure Prevention

• Children and women must avoid contact with unwashed or unclothed application sites in men using testosterone gel. 5, 6
• Patients should wash hands immediately with soap and water after applying gel and cover the application site with clothing after drying. 1, 6
• The application site should be washed thoroughly with soap and water prior to any skin-to-skin contact with another person. 6

Common Pitfalls

• Avoid applying transdermal testosterone to the abdomen, genitals, chest, armpits, or knees—only shoulders and upper arms are appropriate. 6
• Do not interchange different testosterone gel formulations (1% vs 1.62%) as they have different dosing and application instructions. 6
• Patients should avoid swimming or showering for a minimum of 2 hours after gel application to ensure adequate absorption. 6
• Testosterone gel is flammable until dry—patients must avoid fire, flames, or smoking until the gel has dried. 6