What is the typical starting dose for testosterone replacement therapy?

Starting Dose for Testosterone Replacement Therapy

For injectable testosterone (enanthate or cypionate), start with 50-100 mg intramuscularly weekly, which provides more stable testosterone levels than the traditional biweekly dosing regimen. 1, 2

Injectable Formulations: Preferred Starting Approach

Short-Acting Esters (Enanthate/Cypionate)

• Weekly dosing of 50-100 mg intramuscularly is the preferred regimen because it provides significantly more stable testosterone levels with less fluctuation in mood and sexual function compared to biweekly administration 1, 2, 3

• The traditional biweekly dosing of 100-200 mg every 2 weeks remains an acceptable alternative, though it creates problematic fluctuations where peak levels occur 2-5 days after injection and often return to baseline by 10-14 days 2, 4

• The FDA-approved dosing range is 50-400 mg every 2-4 weeks, but this wide range reflects older dosing paradigms that are less physiologic 4

• Subcutaneous administration is an increasingly preferred alternative using the same weekly doses (50-100 mg), as it achieves therapeutic testosterone levels equivalent to intramuscular injection with less discomfort and easier self-administration 1, 5, 6

Long-Acting Formulation (Undecanoate)

• Testosterone undecanoate should be initiated at 750 mg intramuscularly, followed by a second dose at 4 weeks, then maintenance dosing of 750 mg every 10 weeks 1, 2

• This formulation must be administered as a gluteal intramuscular injection only and provides fewer yearly injections with less fluctuation in testosterone levels 1

Transdermal Formulations: Alternative First-Line Option

• Testosterone gel 1% (AndroGel) should be started at 50 mg daily, with titration to 100 mg daily based on testosterone levels measured at 2-3 months 1, 2, 3

• Testosterone patches (Androderm) can be initiated at 2-6 mg per 24 hours, though skin reactions occur in up to 66% of users compared to only 5% with gel preparations 1, 2

• Transdermal preparations are increasingly recommended as first-line therapy due to stable physiologic testosterone levels, patient convenience, and lower risk of erythrocytosis compared to injectable formulations 3

Critical Monitoring Requirements

• Measure testosterone levels 2-3 months after treatment initiation or any dose change 1, 2, 3

• For injectable formulations, measure midway between injections and target mid-normal values (450-600 ng/dL) 1, 2

• For transdermal preparations, measure at any time, though peak values occur 6-8 hours after application 3

• Once stable levels are achieved, monitor every 6-12 months including testosterone levels, hematocrit/hemoglobin, PSA, and prostate examination 1, 2, 3

Formulation Selection Algorithm

Choose transdermal gel as first-line when:

• Patient prioritizes convenience and stable levels 3
• Patient has cardiovascular risk factors (injectable testosterone may carry greater cardiovascular risk) 1, 3
• Patient wants to minimize erythrocytosis risk (occurs in 43.8% with IM injections vs 15.4% with transdermal) 1

Choose weekly injectable testosterone when:

• Cost is a primary concern (injectables are relatively inexpensive) 1, 2
• Patient has adherence issues with daily application 3
• Patient cannot tolerate skin contact restrictions required with gels (risk of transfer to partners/children) 1, 2

Choose long-acting undecanoate when:

• Patient desires minimal injection frequency 1
• Patient demonstrates good adherence and can commit to quarterly clinic visits 2

Common Pitfalls to Avoid

• Do not use biweekly dosing of 200 mg or higher without recognizing the significant testosterone fluctuations that cause mood swings and sexual dysfunction in many patients 2

• Do not forget to monitor hematocrit closely with injectable formulations, as erythrocytosis occurs in a dose-dependent manner and is significantly higher with injections than transdermal preparations 1, 3

• Do not prescribe testosterone gel without counseling about transfer risk to partners and children through skin contact 1, 2

• Do not initiate therapy without baseline PSA and digital rectal examination, as prostate monitoring is mandatory throughout treatment 2, 3

• Do not forget to counsel patients that fertility will be greatly compromised during testosterone replacement therapy due to down-regulation of gonadotropins 2