What treatment options are available for a male patient with hypogonadism and a low free testosterone level of 5.2 pg/mL?

Treatment for Low Free Testosterone (5.2 pg/mL)

You need testosterone replacement therapy if you have confirmed biochemical hypogonadism with symptoms of diminished libido or erectile dysfunction. 1

Diagnostic Confirmation Required Before Treatment

Before initiating any therapy, you must complete the following diagnostic steps:

• Repeat morning total testosterone measurement (8-10 AM) on at least one additional separate occasion to confirm persistent hypogonadism, as single measurements are insufficient due to assay variability and diurnal fluctuation 2, 1
• Measure serum LH and FSH levels to distinguish primary (testicular failure with elevated LH/FSH) from secondary (hypothalamic-pituitary dysfunction with low or low-normal LH/FSH) hypogonadism 1, 3
• This distinction is critical: men with secondary hypogonadism who desire fertility must receive gonadotropin therapy (hCG plus FSH), not testosterone, as testosterone causes azoospermia 1, 4

Symptoms That Justify Treatment

Primary symptoms with proven benefit from testosterone therapy:

• Diminished libido and erectile dysfunction show small but significant improvements (standardized mean difference 0.35) 1

Symptoms with minimal or no proven benefit:

• Fatigue, low energy, depressed mood, reduced physical function, or cognitive complaints show little to no effect even with confirmed hypogonadism 1
• The 2025 European Association of Urology guidelines explicitly recommend against testosterone therapy in eugonadal men, even for weight loss, cardiometabolic improvement, cognition, vitality, or physical strength 1

First-Line Treatment Recommendation

Transdermal testosterone gel 1.62% at 40.5 mg daily is the preferred first-line formulation for men with confirmed hypogonadism 1, 5

Why transdermal over injections:

• Provides more stable day-to-day testosterone levels compared to the peak-trough fluctuations of injections 1
• Lower risk of erythrocytosis compared to injectable testosterone 1
• Easier dose titration to achieve target mid-normal testosterone levels (500-600 ng/dL) 1

Application instructions:

• Apply once daily in the morning to clean, dry, intact skin of shoulders and upper arms only 5
• Do not apply to abdomen, genitals, chest, armpits, or knees 5
• Critical safety warning: Children must avoid contact with unwashed or unclothed application sites due to risk of virilization 5

Alternative Treatment: Injectable Testosterone

If cost is a primary concern, intramuscular testosterone cypionate or enanthate 100-200 mg every 2 weeks is more economical (annual cost $156 vs $2,135 for gel) 1

Dosing and monitoring for injections:

• Peak 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
• Do not draw levels at peak (days 2-5) or trough (days 13-14), as this leads to inappropriate dose adjustments 1

Mandatory Pre-Treatment Testing

Before initiating testosterone therapy, document:

• Baseline hematocrit or hemoglobin (treatment is contraindicated if hematocrit >54%) 1
• PSA level and digital rectal examination in men over 40 years 1
• Fertility counseling: Confirm the patient does not desire current or future fertility, as testosterone causes azoospermia 1, 4

Monitoring Requirements During Treatment

Initial monitoring:

• Check testosterone levels at 14 days and 28 days after starting treatment or dose adjustment 5
• Adjust dose based on pre-dose morning testosterone concentration (target 350-750 ng/dL) 5

Long-term monitoring (every 6-12 months once stable):

• Testosterone levels 1
• Hematocrit—withhold treatment if >54% and consider phlebotomy 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

Absolute Contraindications to Testosterone Therapy

• Active desire for fertility preservation (use gonadotropin therapy instead) 1, 4
• Active or treated male breast cancer 1
• Hematocrit >54% 1
• Untreated severe obstructive sleep apnea 1
• Active prostate cancer 1

Expected Treatment Outcomes

Realistic expectations to discuss with patient:

• Small but significant improvements in sexual function and libido (standardized mean difference 0.35) 1
• Modest quality of life improvements, primarily in sexual function domains 1
• Little to no effect on physical functioning, energy, vitality, depressive symptoms, or cognition 1
• Reevaluate at 12 months and discontinue testosterone if no improvement in sexual function, to prevent unnecessary long-term exposure to potential risks without benefit 1

Critical Pitfalls to Avoid

• Never start testosterone without confirming the patient does not desire fertility, as suppression of spermatogenesis may be prolonged (months to years) after discontinuation 4
• Never diagnose hypogonadism based on symptoms alone without confirmed low testosterone on two separate morning measurements 1
• Never prescribe testosterone to eugonadal men (normal testosterone levels), even if symptomatic, as this violates evidence-based guidelines 1
• Never assume testosterone will improve energy, vitality, or physical function, as evidence shows minimal to no benefit in these domains 1