Adult male with low total testosterone, normal albumin, and low‑normal sex hormone‑binding globulin (SHBG) – how should this be interpreted and what are the appropriate next steps in evaluation and management?

Interpretation and Management of Low Total Testosterone with Normal Albumin and Low-Normal SHBG

Initial Interpretation

Your laboratory results show a total testosterone of 240 ng/dL, which is below the diagnostic threshold for hypogonadism (< 300 ng/dL), but this single measurement is insufficient for diagnosis. 1

The low-normal SHBG (19 nmol/L) is critical because it suggests your free testosterone may actually be higher than expected relative to your total testosterone. 2 When SHBG is low, less testosterone is bound to proteins, meaning more is biologically available even though total testosterone appears low. 2

Required Next Steps for Diagnosis

Mandatory Repeat Testing

• Obtain a second fasting morning total testosterone measurement (8–10 AM) on a separate day. Both values must be < 300 ng/dL to confirm biochemical hypogonadism. 1, 3
• Single measurements are unreliable due to significant intra-individual variability and diurnal fluctuation. 1, 4

Essential Free Testosterone Assessment

• Measure free testosterone by equilibrium dialysis (gold standard) or calculate it using the Vermeulen formula. 3, 2
• With your low SHBG, direct immunoassays for free testosterone are particularly unreliable and should be avoided. 2
• If your calculated free testosterone is normal, you do NOT have true hypogonadism regardless of the low total testosterone. 5

Calculate Free Androgen Index (FAI)

• Use the formula: (Total Testosterone ÷ SHBG) × 100 6
• An FAI < 30 indicates true hypogonadism even when total testosterone is borderline. 1
• With your SHBG of 19 and total testosterone of 240, your FAI is approximately 1,263, which is well above 30 and suggests adequate bioavailable testosterone. 1

Diagnostic Algorithm

Step 1: Confirm Persistent Low Testosterone

• If both morning measurements are < 300 ng/dL → proceed to Step 2 1
• If either measurement is ≥ 300 ng/dL → hypogonadism is not confirmed 1

Step 2: Assess Free Testosterone

• If free testosterone is normal → STOP: No testosterone deficiency exists 5
• If free testosterone is low → proceed to Step 3 1

Step 3: Measure LH and FSH

• Low or low-normal LH/FSH → secondary (hypothalamic-pituitary) hypogonadism 1
• Elevated LH/FSH → primary (testicular) hypogonadism 1
• This distinction is mandatory because it determines treatment options and fertility implications. 1

Step 4: Additional Workup for Secondary Hypogonadism

• Measure serum prolactin (if elevated > 1.5× upper limit, order pituitary MRI) 1
• If testosterone < 150 ng/dL with LH/FSH < 1.5 IU/L, order pituitary MRI immediately 1
• Screen for reversible causes: obesity, diabetes, sleep apnea, chronic opioid use, hemochromatosis 1

Management Based on Free Testosterone Results

If Free Testosterone is Normal (Most Likely Scenario)

Testosterone replacement therapy is NOT indicated. 5 Instead:

• Address underlying causes of symptoms:

  • Screen for anemia (CBC), diabetes (HbA1c, fasting glucose), thyroid dysfunction (TSH) 5
  • Evaluate for sleep disorders, depression, vitamin D deficiency 1
  • Assess cardiovascular risk factors and metabolic syndrome 1

• Implement lifestyle modifications:

  • If obese (BMI > 30), pursue weight loss through a 500–750 kcal/day caloric deficit 1
  • Structured exercise: ≥ 150 minutes/week moderate-intensity aerobic activity plus resistance training 2–3×/week 1
  • Weight loss of 5–10% can significantly increase endogenous testosterone production 1

If Free Testosterone is Confirmed Low

Treatment is indicated ONLY if you have specific qualifying symptoms:

• Primary symptoms with proven benefit: diminished libido, erectile dysfunction, decreased spontaneous morning erections 1
• Symptoms with minimal/no benefit: fatigue, low energy, depressed mood, poor concentration, reduced physical strength 1

Expected realistic outcomes with testosterone therapy:

• Small improvement in sexual function (standardized mean difference 0.35) 1
• Little to no effect on energy, physical function, mood, or cognition 1

Treatment Options (If Indicated)

First-Line: Transdermal Testosterone Gel

• Testosterone gel 1.62% at 40.5 mg daily 1
• Preferred due to stable day-to-day levels and lower erythrocytosis risk (15% vs. 44% with injectables) 1

Alternative: Intramuscular Injections

• Testosterone cypionate/enanthate 100–200 mg every 2 weeks 1
• More cost-effective ($156/year vs. $2,135/year for gel) 1
• Higher erythrocytosis risk (44% of users) 1

Target Levels

• Aim for mid-normal testosterone (500–600 ng/dL) 1

Monitoring Requirements (If Treatment Initiated)

• 2–3 months: testosterone level, hematocrit, PSA (if > 40 years) 1
• Every 3–6 months (first year): repeat above plus lipid profile, digital rectal exam 1
• Annually thereafter: same panel once stable 1
• Withhold treatment if hematocrit > 54% 1

Critical Pitfalls to Avoid

• Never diagnose hypogonadism on a single testosterone measurement 1
• Never start testosterone without measuring free testosterone when SHBG is abnormal 2
• Never initiate therapy without confirming you do NOT desire future fertility (testosterone causes prolonged azoospermia) 1
• Never expect meaningful improvements in energy, mood, or physical function even with confirmed hypogonadism 1
• Never use testosterone for weight loss, athletic performance, or general vitality enhancement 1

Most Likely Scenario for Your Case

Given your low SHBG (19 nmol/L) and calculated FAI of approximately 1,263, your free testosterone is very likely normal despite the low total testosterone of 240 ng/dL. 1, 2 This represents functional adequacy of testosterone despite low total levels. 2

Bottom line: Repeat morning testosterone, measure free testosterone by equilibrium dialysis or calculation, and if free testosterone is normal, focus on addressing reversible causes of your symptoms rather than pursuing testosterone replacement. 5