What is the evaluation and treatment approach for an adult male patient with low testosterone levels, specifically hypogonadism?

Evaluation and Treatment of Low Testosterone (Hypogonadism) in Adult Males

Diagnostic Confirmation

Diagnosis requires both biochemical confirmation AND clinical symptoms—never treat based on symptoms alone. 1

Laboratory Testing Algorithm

• Measure morning total testosterone (8-10 AM) on two separate occasions to confirm persistent hypogonadism, with levels <300 ng/dL indicating deficiency 1, 2
• If total testosterone is borderline (275-350 ng/dL), measure free testosterone by equilibrium dialysis and sex hormone-binding globulin (SHBG) to distinguish true hypogonadism from SHBG-related decreases 1, 2
• Measure serum LH and FSH to distinguish primary (testicular) from secondary (hypothalamic-pituitary) hypogonadism—this distinction is critical for treatment selection 1
  • Low or low-normal LH/FSH with low testosterone = secondary hypogonadism
  • Elevated LH/FSH with low testosterone = primary hypogonadism 1
• In men with low testosterone AND low/normal LH, measure serum prolactin to screen for hyperprolactinemia 1
• If total testosterone <150 ng/dL with low/normal LH, obtain pituitary MRI regardless of prolactin levels to evaluate for non-secreting adenomas 1

Pre-Treatment Baseline Testing

• Hematocrit/hemoglobin (withhold therapy if hematocrit >50%) 1
• PSA and digital rectal exam in men >40 years (PSA >4.0 ng/mL requires urologic evaluation before starting therapy) 1, 2
• Fasting glucose and lipid panel to assess cardiovascular risk 1

Treatment Selection

The primary indication for testosterone therapy is diminished libido and erectile dysfunction—NOT fatigue, low energy, or mood complaints. 2

Expected Benefits (Set Realistic Expectations)

• Small but significant improvements in sexual function and libido (standardized mean difference 0.35) 2
• Little to no effect on physical functioning, energy, vitality, depressive symptoms, or cognition even in confirmed hypogonadism 2
• Potential improvements in bone mineral density, lean body mass, and metabolic parameters (insulin resistance, lipids) 2, 3

Absolute Contraindications

• Active desire for fertility preservation (testosterone causes azoospermia) 1, 2
• Active breast or prostate cancer 1, 3
• Hematocrit >54% 1, 2
• Untreated severe obstructive sleep apnea 2, 3
• Recent cardiovascular event (myocardial infarction or stroke within 3-6 months) 1, 2, 3

Testosterone Replacement Therapy Options

Transdermal testosterone gel is first-line therapy due to stable day-to-day testosterone levels and lower erythrocytosis risk. 2

First-Line: Transdermal Testosterone Gel 1.62%

• Starting dose: 40.5 mg daily (2 pump actuations) applied to shoulders and upper arms 4
• Dose range: 20.25-81 mg daily (1-4 pump actuations) 4
• Target testosterone levels: 450-600 ng/dL (mid-normal range) 1, 2
• Annual cost: ~$2,135 2
• Critical safety warning: Children and women must avoid contact with application sites due to risk of virilization 4

Alternative: Intramuscular Testosterone Injections

• Testosterone cypionate or enanthate: 100-200 mg every 2 weeks or 50-100 mg weekly 2
• Peak levels occur days 2-5, return to baseline by days 10-14 2
• Higher risk of erythrocytosis compared to transdermal preparations 2
• Annual cost: ~$156 (significantly more economical) 2
• Measure testosterone levels midway between injections (days 5-7) targeting 500-600 ng/dL 2

Special Consideration: Fertility Preservation

If the patient desires fertility, testosterone therapy is absolutely contraindicated. 1, 2

• Use gonadotropin therapy (recombinant hCG plus FSH) instead for men with secondary hypogonadism 1, 2
• This directly stimulates the testes and restores both testosterone production and spermatogenesis 2
• Primary hypogonadism patients cannot respond to gonadotropin therapy and must choose between fertility and testosterone replacement 2

Monitoring Protocol

Initial Monitoring (First Year)

• Testosterone levels at 2-3 months after initiation or dose change, then every 6-12 months once stable 2, 3
• Hematocrit at each visit—withhold treatment if >54% and consider phlebotomy 1, 2
• PSA monitoring in men >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
• Assess symptomatic response, particularly sexual function 2

Long-Term Monitoring

• Discontinue therapy if no improvement in sexual function after 12 months to prevent unnecessary exposure to risks without benefit 2
• Continue monitoring testosterone, hematocrit, and PSA every 6-12 months 2, 3
• Evaluate for cardiovascular symptoms (chest pain, shortness of breath, dizziness) at each visit 1

Lifestyle Modifications (Adjunctive Therapy)

For men with obesity-associated secondary hypogonadism, attempt weight loss BEFORE initiating testosterone therapy. 1, 2

• Weight loss through low-calorie diets can improve testosterone levels without medication 1, 2
• Regular physical activity and exercise should be encouraged 1
• These interventions may obviate the need for pharmacologic therapy in some patients 2

Critical Pitfalls to Avoid

• Never diagnose hypogonadism based on symptoms alone without biochemical confirmation 1, 2
• Never start testosterone without confirming the patient does not desire fertility 2
• Never use testosterone therapy in eugonadal men (normal testosterone levels) even if symptomatic—this violates evidence-based guidelines 2
• Never draw testosterone levels at peak (days 2-5) or trough (days 13-14) for injectable formulations—measure midway between injections 2
• Never assume age-related decline justifies treatment—safety and efficacy in "late-onset hypogonadism" are not established 4