What is the recommended subcutaneous (sub q) testosterone replacement therapy (TRT) dosage for a male patient with hypogonadism?

Subcutaneous Testosterone Dosing for Male Hypogonadism

Subcutaneous testosterone is not a standard FDA-approved route for testosterone replacement therapy in male hypogonadism, and current guidelines do not provide specific dosing recommendations for subcutaneous administration. 1

Standard Testosterone Replacement Therapy Formulations

The evidence-based treatment options for confirmed male hypogonadism include:

First-Line: Transdermal Testosterone Gel

• Transdermal testosterone gel 1.62% at 40.5 mg daily is the preferred first-line formulation due to more stable day-to-day testosterone levels and lower risk of erythrocytosis compared to injectable preparations 1
• Provides physiological testosterone patterns with minimal fluctuation 2, 3
• Annual cost approximately $2,135, though 71% of patients prefer it for convenience and ease of use 1

Alternative: Intramuscular Injections

• Testosterone cypionate or enanthate 100-200 mg intramuscularly every 2 weeks (or 50-100 mg weekly for more stable levels) 1
• FDA-approved dosing range is 50-400 mg every 2-4 weeks 1
• Peak serum levels occur 2-5 days after injection, with return to baseline by days 10-14 1
• Measure testosterone levels midway between injections (days 5-7), targeting mid-normal values of 500-600 ng/dL 1
• Annual cost approximately $156, making it the most economical option 1
• Higher risk of erythrocytosis compared to transdermal preparations 1

Third-Line: Long-Acting Injectable

• Testosterone undecanoate 750 mg initially, repeat at 4 weeks, then every 10 weeks 1
• Provides fewer yearly injections with more stable levels 1
• Improves patient compliance for life-long treatment 2

Critical Diagnostic Requirements Before Initiating Any Testosterone Therapy

You must confirm both biochemical hypogonadism AND specific symptoms:

• Two separate morning total testosterone measurements (8-10 AM) below 300 ng/dL are required to establish hypogonadism 1
• Measure free testosterone by equilibrium dialysis in men with obesity or borderline total testosterone 1
• Obtain LH and FSH levels to distinguish primary from secondary hypogonadism 1
• Primary indication is diminished libido and erectile dysfunction—not fatigue, low energy, or physical function 1, 4

Expected Treatment Outcomes

• Small but significant improvements in sexual function and libido (standardized mean difference 0.35) 1, 4
• Modest quality of life improvements, primarily in sexual function domains 4
• Little to no effect on physical functioning, energy, vitality, depressive symptoms, or cognition 1, 4
• Minimal improvements in energy and fatigue (SMD 0.17) 1

Absolute Contraindications

• Active desire for fertility preservation—testosterone suppresses spermatogenesis and causes prolonged azoospermia; use gonadotropin therapy (hCG plus FSH) instead 1, 4
• Active or treated male breast cancer 1, 4
• Hematocrit >54% 1, 4
• Untreated severe obstructive sleep apnea 1

Monitoring Requirements

• Testosterone levels at 2-3 months after initiation, then every 6-12 months once stable 1
• Hematocrit at each visit—withhold treatment if >54% and consider phlebotomy in high-risk cases 1
• PSA levels in men over 40 years—refer for urologic evaluation if PSA increases >1.0 ng/mL in first 6 months or >0.4 ng/mL per year thereafter 1
• Digital rectal examination to assess for prostate abnormalities 1

Critical Clinical Pitfall

Approximately 20-30% of men receiving testosterone in the United States do not have documented low testosterone levels before treatment initiation, representing inappropriate prescribing that violates evidence-based guidelines 4. Never initiate testosterone based on symptoms alone without confirmed biochemical hypogonadism 1.

Reevaluation Strategy

Discontinue testosterone if no improvement in sexual function after 12 months, as this prevents unnecessary long-term exposure to potential risks without benefit 1, 5.