What are the recommended routes of administration for testosterone in adult males with hypogonadism?

Routes of Testosterone Administration for Adult Male Hypogonadism

For adult males with confirmed hypogonadism, intramuscular testosterone injections (cypionate or enanthate) should be the first-line treatment due to significantly lower cost compared to transdermal formulations, with similar clinical effectiveness. 1

Primary Recommendation: Intramuscular Injections

The American College of Physicians specifically recommends intramuscular rather than transdermal formulations when initiating testosterone treatment, as costs are considerably lower for intramuscular preparations. 1 The annual cost difference is substantial: $156.24 for intramuscular versus $2,135.32 for transdermal formulations. 2

Intramuscular Administration Details:

• Dosing: Testosterone cypionate or enanthate 50-400 mg every 2-4 weeks 2, 3
• Pharmacokinetics: Peak serum levels occur 2-5 days after injection, with return to baseline typically observed 10-14 days after injection 2
• Monitoring: Measure testosterone levels midway between injections, targeting a mid-normal value of 500-600 ng/dL 2
• Important caveat: Higher risk of erythrocytosis compared to transdermal preparations 2

Alternative Route: Transdermal Preparations

Transdermal testosterone should be considered when patients refuse intramuscular injections or when cost is not a limiting factor. 4

Transdermal Gel Administration:

• FDA-approved starting dose: 40.5 mg testosterone (2 pump actuations) applied once daily in the morning 5
• Application site: Clean, dry, intact skin of the shoulders and upper arms only 5
• Explicitly avoid: Abdomen, genitals, chest, armpits (axillae), or knees 5
• Advantages: More stable day-to-day testosterone levels, no injection discomfort 2, 4
• Disadvantages: Higher cost, risk of secondary transfer to partners or children through skin contact 4, 5

Critical Safety Measures for Transdermal:

• Wash hands immediately with soap and water after application 5
• Cover application site with clothing after gel has dried 5
• Avoid swimming or showering for minimum 2 hours after application 5
• Wash application site thoroughly with soap and water before any anticipated skin-to-skin contact 5

Third-Line Option: Long-Acting Injectable

Testosterone undecanoate can be used as a third-line option for patients who prefer fewer injections:

• Dosing: 750 mg initially, repeat at 4 weeks, then every 10 weeks 2
• Advantages: Fewer yearly injections, more stable testosterone levels 2
• Monitoring: Target mid-normal testosterone levels (500-600 ng/dL) measured as trough levels before next injection 3

Emerging Alternative: Subcutaneous Injection

Subcutaneous testosterone injections represent an effective alternative to intramuscular administration:

• Dosing: Testosterone cypionate or enanthate 50-150 mg weekly (median 75-80 mg) 6
• Advantages: Less discomfort, can be self-administered, effective across wide range of body mass index 6
• Patient preference: In one study, 20 out of 22 patients who switched from IM to SC had marked preference for subcutaneous route 6

Routes to Avoid or Use with Caution

Oral Testosterone Undecanoate:

• FDA explicitly contraindicates oral testosterone undecanoate for age-related hypogonadism not associated with structural or genetic etiologies 3
• Variable absorption and large fluctuations in plasma testosterone levels 7

Testosterone Patches:

• Frequent skin reactions limit tolerability 7
• Applied to back, abdomen, upper thighs, or upper arms 4
• While providing stable levels, patient acceptance is lower due to skin irritation 4

Monitoring Requirements (All Routes)

• Initial monitoring: Testosterone levels at 2-3 months after treatment initiation and after any dose change 2, 3
• Ongoing monitoring: Every 6-12 months once stable 2
• Hematocrit monitoring: Check periodically and withhold treatment if >54% 2, 3
• PSA monitoring: Check in men over 40 years 2, 3

Clinical Decision Algorithm

1. First choice: Intramuscular testosterone cypionate/enanthate every 2-4 weeks (cost-effective, proven efficacy) 1, 2

2. If patient refuses IM injections: Transdermal gel to shoulders and upper arms daily 4, 5

3. If patient desires fewer injections: Testosterone undecanoate every 10 weeks 2

4. If patient prefers self-administration with less discomfort: Subcutaneous weekly injections 6

Common pitfall to avoid: Do not apply transdermal testosterone to sites other than shoulders and upper arms, as this can alter absorption and increase risk of transfer to others. 5