What is the recommended treatment for low testosterone levels using injections?

Testosterone Injection Treatment for Low Testosterone

For men with confirmed hypogonadism, intramuscular testosterone injections are recommended as the preferred initial formulation over transdermal preparations due to significantly lower cost ($156 vs $2,135 annually) with equivalent clinical effectiveness and safety profiles. 1, 2

Diagnostic Confirmation Required Before Treatment

Before initiating any testosterone therapy, proper diagnosis is essential:

• Measure morning (8-10 AM) total testosterone on two separate occasions to confirm low levels 1
• Measure free testosterone by equilibrium dialysis in men with obesity, as they may have falsely low total testosterone due to low sex hormone-binding globulin 1
• Obtain LH and FSH levels to distinguish primary (testicular) from secondary (pituitary-hypothalamic) hypogonadism 1
• If secondary hypogonadism is identified, measure serum prolactin, iron saturation, and consider pituitary MRI to rule out structural causes 1

Indications for Treatment

Testosterone replacement should only be initiated in men with:

• Documented low testosterone on at least 2 separate morning measurements AND clinical symptoms of hypogonadism (decreased libido, erectile dysfunction, reduced energy, decreased muscle mass, hot flashes, gynecomastia) 1
• Primary indication is sexual dysfunction improvement - this is the only outcome with sufficient evidence to support treatment 1
• Do NOT initiate testosterone solely to improve energy, vitality, physical function, or cognition, as evidence does not support benefit for these outcomes 1

Injectable Testosterone Dosing Regimens

Standard Intramuscular Dosing

FDA-approved dosing for testosterone cypionate or enanthate:

• 50-400 mg intramuscularly every 2-4 weeks 3
• Most common regimen: 100-200 mg every 2 weeks 1, 4, 3
• Preferred alternative: 50-100 mg weekly to reduce problematic peaks and troughs 4, 5
• Administer deep in the gluteal muscle 3

Subcutaneous Administration Option

Subcutaneous injection is an effective alternative to intramuscular:

• Use the same dosing as intramuscular: 50-100 mg weekly or 100-200 mg every 2 weeks 4, 6
• Weekly dosing (50 mg) is increasingly preferred as it provides more stable levels and reduces time in supratherapeutic and subtherapeutic ranges 4, 5
• Subcutaneous route achieves normal male testosterone levels with doses of 50-150 mg weekly (median 75-80 mg) 6
• Patients overwhelmingly prefer subcutaneous over intramuscular (20 of 22 patients showed marked preference) due to reduced discomfort and ability to self-administer 6
• Virtually painless with minimal injection site reactions (>95% reported no pain) 7

Long-Acting Formulation

Testosterone undecanoate offers extended dosing intervals:

• 1000 mg intramuscularly every 12 weeks after initial loading doses 8, 9
• Provides stable testosterone levels with only 4 injections per year 9
• Equivalent efficacy and safety to standard testosterone enanthate 9

Monitoring Protocol

Initial Monitoring

• Check testosterone levels 2-3 months after treatment initiation or dose adjustment 1, 2, 4, 5
• For injections: measure at trough (midway between injections) targeting mid-normal values of 500-600 ng/dL 2, 4, 5
• Monitor hematocrit/hemoglobin and PSA at baseline and during treatment 5

Ongoing Monitoring

• Once stable levels confirmed, monitor every 6-12 months 4, 5
• Reassess symptoms within 12 months and periodically thereafter 1
• Discontinue treatment if no improvement in sexual function after 12 months 1

Critical Safety Considerations

Cardiovascular Risk

Injectable testosterone carries cardiovascular concerns:

• FDA required labeling changes in 2015 regarding possible increased risk of heart attack and stroke 5
• Injections associated with greater cardiovascular risk than gels due to fluctuating levels causing extended periods in both supratherapeutic and subtherapeutic ranges 4, 5
• Weekly dosing reduces cardiovascular risk compared to biweekly dosing by providing more stable levels 4, 5

Hematologic Risk

Erythrocytosis is a significant concern with injections:

• Injections carry significantly higher risk of erythrocytosis than topical preparations 5
• Risk associated with supraphysiologic bioavailable testosterone levels that occur with injection peaks 5
• Regular hematocrit monitoring is mandatory, especially with injectable formulations 5

Other Important Warnings

• Testosterone therapy causes testicular atrophy and reduced fertility during treatment 5
• Contraindicated in men with prostate cancer or breast cancer 3
• Monitor PSA levels regularly given theoretical prostate cancer concerns 5, 9

Clinical Decision Algorithm for Injection Choice

When intramuscular injections are chosen:

1. Start with weekly dosing (50-100 mg) rather than biweekly to minimize cardiovascular risk and provide stable levels 4, 5
2. Consider subcutaneous route for improved patient satisfaction, reduced pain, and ability to self-administer 6, 7
3. Reserve long-acting testosterone undecanoate (every 12 weeks) for patients with adherence concerns or strong preference for infrequent dosing 8, 9

Common pitfall: Biweekly dosing (100-200 mg every 2 weeks) remains widely used but creates problematic fluctuations with supraphysiologic peaks and subtherapeutic troughs, increasing cardiovascular risk and erythrocytosis 4, 5, 10