What is the typical dose and scheduling for testosterone replacement therapy (TRT) in a male patient with hypogonadism?

Testosterone Replacement Therapy Dosing for Male Hypogonadism

For adult males with confirmed hypogonadism, intramuscular testosterone cypionate or enanthate should be administered at 200 mg every 2 weeks or 100 mg weekly, targeting mid-normal testosterone levels of 500-600 ng/dL. 1, 2, 3

Diagnostic Confirmation Required Before Initiating Treatment

Before starting any testosterone therapy, you must confirm biochemical hypogonadism with two separate morning (8-10 AM) total testosterone measurements below 300 ng/dL, along with specific symptoms such as diminished libido or erectile dysfunction. 1, 4 Single measurements are insufficient due to assay variability and diurnal fluctuation. 1

Additionally, measure LH and FSH to distinguish primary from secondary hypogonadism, as this distinction has critical treatment implications for fertility preservation. 1 Men with secondary hypogonadism who desire fertility must receive gonadotropin therapy (hCG plus FSH) instead—testosterone is absolutely contraindicated in this scenario. 1

Standard Intramuscular Dosing Regimens

First-Line Injectable Options

Testosterone cypionate or enanthate: 200 mg intramuscularly every 2 weeks is the most evidence-based regimen, effectively suppressing elevated LH and FSH to normal range while maintaining physiologic testosterone levels. 3, 5 This dosing was specifically validated in controlled trials showing optimal gonadotropin suppression. 5

Alternative weekly dosing: 50-100 mg intramuscularly weekly provides more stable serum testosterone levels compared to biweekly administration and may be preferred for patients experiencing mood or energy fluctuations with the longer interval. 1, 2

The FDA-approved dosing range is 50-400 mg every 2-4 weeks, but doses exceeding 200 mg every 2 weeks significantly increase erythrocytosis risk without additional clinical benefit. 2, 6 The 300 mg every 3 weeks regimen showed nearly equivalent efficacy to 200 mg every 2 weeks in suppressing gonadotropins, but offers no practical advantage. 5

Peak and Trough Dynamics

Peak serum testosterone occurs 2-5 days after injection, with return to baseline by days 10-14. 1, 3 This pharmacokinetic profile explains why some patients experience end-of-cycle symptoms with biweekly dosing, making weekly administration preferable in such cases. 1

Alternative Transdermal Formulation

Transdermal testosterone gel 1.62% at 40.5 mg daily (2 pump actuations) applied to shoulders and upper arms is often favored as first-line therapy due to more stable day-to-day testosterone levels and lower erythrocytosis risk compared to injections. 1, 4 The dose can be adjusted between 20.25 mg (1 pump) and 81 mg (4 pumps) based on serum levels. 4

However, intramuscular testosterone is significantly more economical (annual cost $156 vs $2,135 for transdermal), making it the preferred choice when cost is a concern. 1 Patient preference varies—some prefer injections for lower cost, while others prefer gel for convenience and avoidance of injection-related fluctuations. 1

Monitoring Protocol

Initial Monitoring

Measure testosterone levels midway between injections (days 5-7 for biweekly dosing) at 2-3 months after treatment initiation, targeting mid-normal values of 500-600 ng/dL. 1, 2, 3 For weekly dosing, measure at trough (just before next injection). 2

Ongoing Monitoring

Once stable levels are confirmed, monitor testosterone every 6-12 months. 1, 3

Hematocrit must be monitored regularly—withhold treatment if hematocrit exceeds 54% and consider phlebotomy in high-risk cases. 1, 2, 3 Injectable testosterone carries higher erythrocytosis risk (up to 44%) compared to transdermal preparations (15.4%). 7, 8

For men over 40 years, monitor PSA levels before initiating therapy and periodically during treatment, with urologic referral if PSA increases >1.0 ng/mL in the first 6 months or >0.4 ng/mL per year thereafter. 1, 3

Expected Treatment Outcomes

Testosterone therapy produces small but significant improvements in sexual function and libido (standardized mean difference 0.35), which is the primary indication for treatment. 7, 1 Quality of life improvements are modest, primarily in sexual function domains. 1

Critically, testosterone produces little to no effect on physical functioning, energy, vitality, depressive symptoms, or cognition, even in confirmed hypogonadism. 7, 1 If no improvement in sexual function is seen after 12 months, discontinue treatment to prevent unnecessary long-term exposure to potential risks without benefit. 1

Absolute Contraindications

• Active desire for fertility preservation (testosterone causes azoospermia; use gonadotropin therapy instead) 1, 3
• Active or treated male breast cancer 1, 3
• Hematocrit >54% 1, 2
• Recent cardiovascular events within past 3-6 months 1, 3
• Untreated severe obstructive sleep apnea 1

Critical Pitfalls to Avoid

Never start testosterone without confirming the patient does not desire fertility, as suppression of spermatogenesis can be prolonged even after discontinuation. 1

Never diagnose hypogonadism based on symptoms alone—approximately 20-30% of men receiving testosterone in the United States lack documented low testosterone levels before treatment initiation, violating evidence-based guidelines. 1

Never use weekly doses exceeding 200 mg, as this enters the supraphysiologic range and significantly increases adverse effects, particularly erythrocytosis and HDL reduction, without additional clinical benefit. 7, 2

For men with obesity-associated secondary hypogonadism, attempt weight loss through low-calorie diets and regular exercise before initiating testosterone, as this can improve testosterone levels without medication. 7, 1