I am an adult male with a total serum testosterone of 361 ng/dL (low‑normal) and a directly measured free testosterone of 5.9 pg/mL (low); what interventions are recommended?

Interventions for Low-Normal Total Testosterone (361 ng/dL) with Low Free Testosterone (5.9 pg/mL)

You should confirm true biochemical hypogonadism with repeat morning testing before initiating any treatment, and if confirmed, testosterone replacement therapy is indicated only if you have specific symptoms of diminished libido or erectile dysfunction—not for fatigue, low energy, or mood complaints. 1, 2

Diagnostic Confirmation Required First

Your total testosterone of 361 ng/dL sits in a "gray zone" just above the diagnostic threshold of 300 ng/dL, while your free testosterone of 5.9 pg/mL appears low. 2, 3 However, you cannot proceed with treatment based on a single measurement. 2

Mandatory Next Steps

• Repeat morning total testosterone (8–10 AM) on at least one additional occasion to confirm persistent levels, as single measurements are unreliable due to diurnal variation and assay differences. 2, 3
• Measure free testosterone by equilibrium dialysis (the gold standard method) rather than relying on direct immunoassay, which is notoriously inaccurate. 2, 3, 4
• Measure sex hormone-binding globulin (SHBG) and albumin to calculate free testosterone and verify your direct measurement, as discordance between borderline-low total testosterone and clearly low free testosterone may indicate true biochemical hypogonadism. 2, 3
• Measure LH and FSH once low testosterone is confirmed, because distinguishing primary (testicular) from secondary (hypothalamic-pituitary) hypogonadism is critical for treatment selection and fertility counseling. 2

The 2020 American College of Physicians guideline and 2025 European Association of Urology guideline both require two separate morning measurements below 300 ng/dL to establish hypogonadism. 1, 2 Your single value of 361 ng/dL does not meet this threshold. 2

If Repeat Testing Confirms Low Testosterone (<300 ng/dL on Two Occasions)

Symptom Assessment Determines Treatment Eligibility

Testosterone therapy is indicated ONLY for diminished libido and erectile dysfunction. 1, 2 The 2020 ACP guideline explicitly recommends against testosterone treatment for energy, vitality, physical function, or cognition, as these show little to no benefit even in confirmed hypogonadism. 1

• If you have diminished libido or erectile dysfunction: Proceed with treatment algorithm below. 1, 2
• If your primary complaints are fatigue, low energy, or mood: Testosterone therapy will not help—investigate alternative causes (sleep disorders, thyroid dysfunction, anemia, vitamin D deficiency, depression, metabolic syndrome). 1, 3

Treatment Selection Algorithm

Step 1: Rule Out Fertility Concerns

• If you desire fertility preservation now or in the future: Testosterone therapy is absolutely contraindicated because it causes prolonged, potentially irreversible azoospermia. 2 Instead, you require gonadotropin therapy (hCG plus FSH) if you have secondary hypogonadism. 2

Step 2: Choose Testosterone Formulation

Transdermal testosterone gel 1.62% at 40.5 mg daily is the preferred first-line formulation because it provides more stable day-to-day testosterone levels and carries lower risk of erythrocytosis (15.4%) compared to injectable testosterone (43.8%). 2

• Alternative if cost is a concern: Intramuscular testosterone cypionate or enanthate 100–200 mg every 2 weeks costs approximately $156/year versus $2,135/year for transdermal gel, with similar clinical effectiveness. 1, 2
• Target testosterone levels: Mid-normal range of 500–600 ng/dL. 2

Step 3: Mandatory Pre-Treatment Testing

Before starting testosterone, you must have: 2

• Baseline hematocrit/hemoglobin (treatment is contraindicated if hematocrit >54%)
• PSA level and digital rectal examination (if age ≥40 years)
• Confirmation that you do not desire fertility

Step 4: Monitoring Schedule

• At 2–3 months: Check testosterone levels, hematocrit, and assess symptom response. 2
• Every 6–12 months thereafter: Monitor testosterone, hematocrit, PSA (if age ≥40), and symptom response. 2
• At 12 months: If no improvement in sexual function, discontinue testosterone to prevent unnecessary long-term exposure without benefit. 2

Expected Outcomes with Testosterone Therapy

Set realistic expectations: 1

• Sexual function and libido: Small but significant improvement (standardized mean difference 0.35)
• Physical function, energy, vitality, cognition: Little to no effect
• Mood/depression: Less-than-small improvement (SMD 0.19)
• Quality of life: Modest improvements, primarily driven by sexual function domains

If Repeat Testing Shows Testosterone Remains 231–346 ng/dL (Gray Zone)

A 4–6 month therapeutic trial may be considered after careful risk-benefit discussion, but only if you have diminished libido or erectile dysfunction. 2 Continue beyond 6 months only if clinical benefit is demonstrated. 2

If Repeat Testing Shows Testosterone >350 ng/dL

Testosterone replacement is not indicated, regardless of symptoms. 2 The European Association of Urology explicitly recommends against testosterone therapy in men with normal testosterone levels, even for weight loss, cardiometabolic improvement, cognition, vitality, or physical strength. 2, 3

Instead, systematically evaluate for: 3

• Sleep disorders (especially obstructive sleep apnea)
• Thyroid dysfunction
• Anemia
• Vitamin D deficiency
• Depression
• Metabolic syndrome components

Critical Pitfalls to Avoid

• Never diagnose hypogonadism on a single testosterone measurement. 2
• Never test outside morning hours (8–10 AM), as later measurements risk false-positive diagnoses. 2
• Never rely on direct immunoassay free testosterone—use equilibrium dialysis or calculated values. 2, 4
• Never start testosterone without confirming the patient does not desire fertility, as this causes irreversible suppression of spermatogenesis. 2
• Never expect meaningful improvements in energy, physical function, or cognition even with confirmed hypogonadism. 1
• Never omit LH/FSH testing once low testosterone is confirmed, because the distinction between primary and secondary hypogonadism directs therapy and fertility counseling. 2

Special Consideration: Obesity-Associated Hypogonadism

If you are obese, your low-normal total testosterone may reflect reduced SHBG with normal free testosterone rather than true hypogonadism. 3, 5 Weight loss through low-calorie diets (500–750 kcal/day deficit) and regular exercise (minimum 150 minutes/week moderate-intensity aerobic exercise plus resistance training 2–3 times weekly) should be attempted first, as this can reverse obesity-associated secondary hypogonadism without medication. 2