What is the maximum dose for testosterone replacement therapy (TRT) in a male patient with hypogonadism and a testosterone level of 198 ng/dL?

Maximum Dose for TRT with Testosterone Level of 198 ng/dL

For a patient with confirmed hypogonadism (testosterone 198 ng/dL), the FDA-approved maximum dose is 400 mg intramuscular testosterone cypionate every 2-4 weeks, though most patients achieve target levels with 100-200 mg every 2 weeks. 1

Diagnostic Confirmation Required First

Before initiating therapy, you must confirm persistent hypogonadism with:

• A second fasting morning testosterone measurement (8-10 AM) to verify the low level, as single measurements are insufficient due to assay variability 2, 3
• Assessment of LH and FSH levels to distinguish primary from secondary hypogonadism, which has critical treatment implications including fertility preservation 2
• Documentation that the patient has hypogonadal symptoms, particularly diminished libido and erectile dysfunction, as biochemical hypogonadism alone without symptoms does not warrant treatment 2, 3

Recommended Starting Dose and Titration

Start with testosterone cypionate 100-200 mg intramuscular every 2 weeks, not the maximum dose 2. The rationale:

• Your patient's testosterone of 198 ng/dL is well below the diagnostic threshold of <300 ng/dL, confirming hypogonadism 3, 4
• Target mid-normal testosterone levels of 450-600 ng/dL, not supraphysiologic levels 2, 3
• Starting at maximum dose (400 mg) risks erythrocytosis and supraphysiologic peaks 2

Monitoring and Dose Adjustment Protocol

• Measure testosterone levels at 2-3 months after initiation, drawn midway between injections (days 5-7 after injection) 2, 3
• Target range: 500-600 ng/dL at mid-cycle 2
• If levels remain suboptimal AND symptoms persist, increase dose incrementally toward the 400 mg maximum 1
• Once stable, monitor every 6-12 months 2, 3

Critical Safety Monitoring

Monitor hematocrit at each visit—withhold treatment if >54% and consider phlebotomy, as injectable testosterone carries higher erythrocytosis risk than transdermal preparations 2, 3

Additional required monitoring:

• 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 2
• Digital rectal examination to assess for prostate abnormalities 2

Absolute Contraindications to Starting Therapy

Do not initiate testosterone if the patient:

• Desires fertility preservation—testosterone causes azoospermia; use gonadotropin therapy (hCG plus FSH) instead 2
• Has active or treated male breast cancer 2
• Has hematocrit >54% 2, 3
• Has untreated severe obstructive sleep apnea 2
• Had cardiovascular events within the past 3-6 months 3

Why Not Start at Maximum Dose

Starting at 400 mg every 2-4 weeks is inappropriate because:

• Peak testosterone occurs 2-5 days post-injection, often reaching supraphysiologic levels (>2000 ng/dL), followed by return to baseline by days 10-14 2, 5
• This creates dramatic fluctuations that increase adverse effects, particularly erythrocytosis 2, 5
• The goal is stable, mid-normal testosterone levels (450-600 ng/dL), not maximum levels 3
• Most patients achieve target levels with 100-200 mg every 2 weeks 2

Alternative Formulation Consideration

Transdermal testosterone gel (40.5 mg daily) is preferred as first-line therapy over injectable testosterone due to more stable day-to-day levels and lower erythrocytosis risk 2. However, if cost is a concern, intramuscular testosterone is more economical (annual cost $156 vs $2,135 for transdermal) 2.

Expected Treatment Outcomes

Set realistic expectations with your patient:

• Small but significant improvements in sexual function and libido (standardized mean difference 0.35) 2
• Little to no effect on physical functioning, energy, vitality, or cognition, even with confirmed hypogonadism 2
• Modest quality of life improvements, primarily in sexual function domains 2
• Reevaluate at 12 months—discontinue if no improvement in sexual function to prevent unnecessary long-term exposure 2

Common Pitfall to Avoid

Never assume higher doses are better. The 2023 TRAVERSE study used transdermal testosterone with dose adjustments targeting 350-750 ng/dL and found no increased stroke risk, supporting the use of physiologic replacement doses rather than supraphysiologic levels 6. Using maximum doses increases adverse effects without improving outcomes 2, 5.