What is the best course of action for a patient with low total testosterone, low free and bioavailable testosterone, and normal sex hormone-binding globulin levels, presenting with symptoms of androgen deficiency?

Interpretation and Management of Your Testosterone Results

Your Laboratory Values Indicate Compensated Testosterone Production, Not True Hypogonadism

Your total testosterone of 450 ng/dL is within the normal adult male range (above the diagnostic threshold of 300 ng/dL for hypogonadism), and your elevated SHBG of 61 is causing the low free and bioavailable testosterone values—this represents a compensatory state where your pituitary is successfully maintaining adequate testosterone production, not true testosterone deficiency. 1, 2

Understanding Your Results

Your laboratory pattern shows:

• Total testosterone 450 ng/dL: This is solidly within the normal range (reference 348-723 ng/dL), well above the 300 ng/dL threshold required for diagnosing hypogonadism 1, 3
• Free testosterone 34.5 pg/mL: Low (reference >70 pg/mL) 3
• Bioavailable testosterone 74 ng/dL: Low (reference >53 nmol/L or approximately 150 ng/dL) 4
• SHBG 61 nmol/L: Elevated (typical reference 10-57 nmol/L) 2

The elevated SHBG is binding more testosterone, reducing the free fraction, but your pituitary has compensated by increasing LH secretion to stimulate more testicular production, maintaining your total testosterone in the normal range. 2

Critical Next Step: Measure LH and FSH

You must measure serum LH and FSH levels before any treatment decisions are made. 1, 2

• If LH is normal or elevated: This confirms your pituitary is appropriately compensating for the elevated SHBG, and you do not have true hypogonadism despite the low free testosterone values 2
• If LH is low or low-normal: This would indicate secondary hypogonadism requiring further pituitary evaluation 1, 5

Do You Have Symptoms of Testosterone Deficiency?

The diagnosis of testosterone deficiency requires BOTH low testosterone measurements AND specific symptoms. 1, 6 Testosterone therapy should never be initiated based on laboratory values alone. 1

Key symptoms to assess:

• Sexual symptoms: Reduced libido, erectile dysfunction, decreased spontaneous erections 1, 5
• Physical symptoms: Reduced energy, decreased endurance, diminished work/physical performance, fatigue 1, 5
• Body composition changes: Loss of muscle mass, increased body fat 1, 5
• Mood symptoms: Depression, reduced motivation, poor concentration, irritability 1, 5

Treatment Algorithm Based on Your Specific Situation

If You Have NO Significant Symptoms:

No treatment is indicated. Your testosterone levels are normal, and testosterone therapy in men with normal total testosterone provides minimal to no benefit for energy, vitality, physical function, or cognition, even when free testosterone is low. 5 Approximately 25% of men receiving testosterone therapy do not meet diagnostic criteria for hypogonadism. 1

If You Have Symptoms AND LH is Normal/Elevated:

Address the underlying cause of elevated SHBG first before considering any hormonal intervention: 5, 2

• Weight loss and exercise: If you have obesity or metabolic syndrome, this can normalize SHBG and improve free testosterone without medication 5
• Evaluate for hyperthyroidism: A common cause of elevated SHBG 2
• Review medications: Anticonvulsants and estrogens can elevate SHBG 2
• Assess liver function: Cirrhosis can increase SHBG 5

If symptoms persist after addressing SHBG causes, selective estrogen receptor modulators (SERMs) may be considered as an alternative to testosterone replacement in patients with elevated SHBG and normal total testosterone. 5, 2

If You Have Symptoms AND LH is Low:

This indicates true secondary hypogonadism requiring:

• Prolactin measurement to rule out hyperprolactinemia 5
• Pituitary MRI if prolactin is elevated or other pituitary dysfunction is suspected 5
• Fertility assessment: If you desire fertility now or in the future, testosterone therapy is absolutely contraindicated—you would require gonadotropin therapy (hCG plus FSH) instead 5, 7

Critical Pitfall to Avoid

Do not initiate testosterone replacement based solely on low free testosterone values when total testosterone is normal without first measuring LH/FSH and confirming true hypogonadism. 2 Starting testosterone in your situation could:

• Suppress your natural testosterone production unnecessarily 5
• Cause permanent infertility by suppressing spermatogenesis 5, 7
• Expose you to risks (erythrocytosis, cardiovascular events) without addressing the underlying SHBG issue 5

Expected Outcomes If Treatment Were Indicated

Even in confirmed hypogonadism, testosterone therapy produces: 5

• Small improvements in sexual function (standardized mean difference 0.35)
• Minimal to no effect on physical functioning, energy, vitality, or cognition (SMD 0.17 for energy)
• Less-than-small improvements in mood (SMD -0.19)

Monitoring Requirements If Treatment Is Eventually Started

Should you ultimately require testosterone therapy after proper evaluation: 5, 6

• Testosterone levels at 2-3 months, then every 6-12 months
• Hematocrit monitoring (withhold if >54%)
• PSA monitoring if over age 40
• Reassess symptoms at 12 months and discontinue if no improvement in sexual function