What is the typical starting dose for testosterone replacement therapy?

Testosterone Replacement Therapy Starting Dose

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; alternatively, use transdermal gel 40.5-50 mg daily applied to shoulders and upper arms. 1, 2

Injectable Testosterone Formulations

Standard Dosing Regimens

Testosterone enanthate or cypionate:

• Starting dose: 100-200 mg intramuscularly every 2 weeks 1
• Preferred alternative: 50-100 mg weekly for more stable testosterone levels with less fluctuation 1
• Can be self-administered in the thighs or given by another person in the gluteal region 1

Testosterone undecanoate (long-acting):

• Initial dose: 750 mg intramuscularly 1
• Second dose: 750 mg at 4 weeks 1
• Maintenance: 750 mg every 10 weeks thereafter 1
• Must be administered as gluteal intramuscular injection only 1
• Provides fewer yearly injections with less fluctuation in testosterone levels 1

Why Weekly Dosing is Preferred

Weekly administration of 50-100 mg provides significantly more stable testosterone levels compared to biweekly dosing 1. With standard biweekly injections of 200 mg, peak serum levels occur 2-5 days after injection and often return to baseline by 10-14 days, creating problematic fluctuations in mood and sexual function 3. This fluctuation also increases the risk of adverse effects including erythrocytosis and potentially cardiovascular complications 1.

Transdermal Formulations

Gel Preparations (First-Line for Many Patients)

Testosterone gel 1.62%:

• Starting dose: 40.5 mg daily (2 pump actuations or one 40.5 mg packet) 2
• Applied once daily in the morning to shoulders and upper arms only 2
• Do NOT apply to abdomen, genitals, chest, armpits, or knees 2
• Dose range: 20.25 mg (minimum) to 81 mg (maximum) 2

Testosterone gel 1% (AndroGel):

• Starting dose: 50-100 mg daily 1

Testosterone patches (Androderm):

• Starting dose: 2-6 mg per 24 hours 1
• Major limitation: skin reactions occur in up to 66% of users compared to only 5% with gel preparations 3, 1

Critical Safety Considerations for Transdermal Products

• Patients must wash hands immediately with soap and water after application 2
• Cover application sites with clothing after gel dries 2
• Avoid swimming or showering for minimum 2 hours after application 3, 2
• Wash application site thoroughly with soap and water before any skin-to-skin contact with others 2
• Children must avoid contact with unwashed or unclothed application sites due to risk of virilization 2
• Gel is flammable until dry—avoid fire, flames, or smoking 2

Monitoring and Dose Titration

Initial Monitoring Schedule

First follow-up: 1-2 months after initiation to assess efficacy and consider dose escalation if inadequate response with suboptimal testosterone levels 3

Dose titration timing:

• Measure testosterone levels at 14 days and 28 days after starting treatment or any dose adjustment 2
• For injectable formulations, measure midway between injections, targeting mid-normal values 1
• Once stable, monitor every 3-6 months for first year, then yearly thereafter 3

Target Testosterone Levels

Aim for mid- to upper-normal range (approximately 450-600 ng/dL) to optimize treatment response 3, 1. However, if the patient reports adequate clinical response, no dosage adjustment is needed even if levels are in the low-normal range 3.

Dose Adjustment Algorithm for Gel (1.62%)

Pre-dose morning total testosterone:

• >750 ng/dL: Decrease daily dose by 20.25 mg 2
• 350-750 ng/dL: Continue current dose 2
• <350 ng/dL: Increase daily dose by 20.25 mg 2

Dose Adjustment for Injectable Therapy

If clinical response is suboptimal and testosterone levels are in the low-normal range, increase the testosterone dosage 3. If maximal recommended transdermal dose fails to achieve adequate serum testosterone levels, consider switching to intramuscular injection therapy 3.

Baseline Testing Requirements

Before initiating therapy, confirm diagnosis by measuring serum testosterone in the morning on at least two separate days, with both values below normal range 2.

Baseline assessments:

• PSA and digital rectal examination 3
• Hematocrit or hemoglobin 3
• Voiding symptoms (consider International Prostatic Symptoms Score) 3
• History of sleep apnea 3
• Lipid evaluation (optional) 3

Formulation Selection Considerations

Injectable Advantages and Disadvantages

Advantages:

• Relatively inexpensive 1
• Flexible dosing intervals 1

Disadvantages:

• Requires intramuscular injection 1
• Fluctuating serum testosterone levels (especially with biweekly dosing) 1
• Greater cardiovascular risk compared to transdermal preparations, possibly due to fluctuating levels 1
• Higher risk of erythrocytosis (43.8% with IM injections vs 15.4% with transdermal patches) 1
• Local pain, soreness, bruising, erythema, swelling, nodules, or furuncles at injection site 3

Transdermal Gel Advantages and Disadvantages

Advantages:

• Easy application 1
• Good skin tolerability (only 5% experience reactions) 3, 1
• More stable testosterone levels 1
• Lower risk of erythrocytosis 1

Disadvantages:

• Potential for transfer to partners or children 1
• More expensive than injectable formulations 1
• Requires daily application and adherence to safety precautions 2

Common Pitfalls to Avoid

Hematocrit monitoring: If hematocrit rises above reference range, consider temporarily withholding therapy, reducing dosage, or performing phlebotomy 3. Injectable testosterone carries significantly higher risk of erythrocytosis than transdermal preparations 1.

Prostate monitoring: Mandatory monitoring for signs of prostate cancer given concerns about potential stimulation of occult cancer 3. Perform digital rectal examination and measure PSA at each monitoring visit 3.

Fertility counseling: Advise patients that testicular size often diminishes and fertility will be greatly compromised during testosterone replacement therapy due to down-regulation of gonadotropins 3.

Fluid retention: Use cautiously in men with congestive heart failure or renal insufficiency, though fluid retention is generally uncommon and mild 3.

Secondary exposure prevention: This is particularly critical with transdermal formulations—failure to follow proper application and washing protocols can cause virilization in children who come into contact with application sites 2.