In a 48‑year‑old man with chronic alcohol use, hypertension and asthma who has low total, free and bioavailable testosterone, borderline high hemoglobin, and a free‑PSA ratio of 23 %, how should these laboratory results be interpreted and what is the appropriate management for his hypogonadism?

Laboratory Interpretation and Management Approach

Critical First Step: Confirm the Diagnosis of Hypogonadism

Your patient does NOT yet meet diagnostic criteria for hypogonadism, and testosterone replacement therapy should not be initiated at this time. 1, 2, 3

Why the Diagnosis is Not Confirmed

• Total testosterone of 206 ng/dL is below the diagnostic threshold (<300 ng/dL), but hypogonadism requires two separate morning measurements (8–10 AM) on different days to confirm persistent low levels due to diurnal variation and assay variability. 1, 2, 3
• You have only one measurement, which is insufficient for diagnosis regardless of how low the value appears. 1, 2
• Diagnosis requires BOTH biochemical confirmation (two low morning values) AND specific symptoms—particularly diminished libido and erectile dysfunction—which you have not documented in this case. 1, 3, 4

Immediate Next Steps

1. Repeat morning total testosterone (8–10 AM) on at least one additional occasion using the same laboratory to confirm persistent levels <300 ng/dL. 1, 2, 3
2. Measure free testosterone by equilibrium dialysis or calculate it using a validated formula (Vermeulen), as your patient's total testosterone is in the range where free testosterone assessment is mandatory. 1, 2, 3
3. Measure sex hormone-binding globulin (SHBG) to interpret the relationship between total and free testosterone, especially given his chronic alcohol use and comorbidities. 1, 2, 3

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Address the Elevated Hemoglobin BEFORE Any Testosterone Consideration

Hemoglobin 17.6 g/dL (hematocrit likely >52%) is a relative contraindication to testosterone therapy and requires immediate evaluation. 1, 5, 3

Why This Matters

• Hematocrit >54% is an absolute contraindication to starting testosterone therapy per FDA labeling and all major guidelines. 1, 5, 3
• Testosterone therapy causes erythrocytosis in 44% of men on injectable formulations and 15% on transdermal preparations, which would worsen his already elevated hemoglobin. 1
• Elevated blood viscosity from erythrocytosis exacerbates cardiovascular disease, particularly concerning in a 48-year-old with hypertension. 1

Required Workup for Elevated Hemoglobin

• Complete blood count (CBC) with differential to confirm hematocrit and rule out polycythemia vera or secondary erythrocytosis. 2
• Evaluate for secondary causes of erythrocytosis: chronic hypoxemia (sleep apnea, COPD), smoking history, renal pathology, or erythropoietin-secreting tumors. 1, 2
• If hematocrit >54%, testosterone therapy is absolutely contraindicated until the cause is identified and corrected. 1, 5, 3

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Interpret the PSA Result Correctly

PSA "free 23" is ambiguous and requires clarification, but if this represents a free PSA percentage of 23%, it is reassuring and does not suggest prostate cancer. 1, 3

What You Need

• Obtain total PSA and calculate the free-to-total PSA ratio if not already done. 1, 3
• Total PSA >4.0 ng/mL requires urologic evaluation and documented negative prostate biopsy before initiating testosterone therapy. 1, 5, 3
• Perform digital rectal examination (DRE) to assess for palpable prostate nodules or induration, which are absolute contraindications to testosterone therapy. 1, 5, 3

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Distinguish Primary from Secondary Hypogonadism

Once you confirm persistent low testosterone with a second morning measurement, you MUST measure LH and FSH to classify the type of hypogonadism, as this has critical treatment implications. 1, 2, 3

Why This Distinction Matters

• Secondary hypogonadism (low or low-normal LH/FSH with low testosterone) may be reversible through weight loss, alcohol cessation, and treatment of underlying conditions. 1, 6, 4
• Primary hypogonadism (elevated LH/FSH with low testosterone) indicates testicular failure and requires testosterone replacement if symptomatic. 1, 6, 3
• If the patient desires fertility preservation, testosterone therapy is absolutely contraindicated; gonadotropin therapy (hCG + FSH) is mandatory for secondary hypogonadism. 1, 3, 4

Additional Workup for Secondary Hypogonadism

• Measure serum prolactin if LH is low or low-normal, as hyperprolactinemia suppresses gonadotropins and causes hypogonadism. 1, 2, 3
• Consider pituitary MRI if prolactin is elevated or if there are signs of pituitary dysfunction (visual field defects, headaches). 1, 2
• Evaluate for reversible causes: chronic alcohol use (your patient), obesity, metabolic syndrome, medications (opiates, corticosteroids), chronic illness, or sleep apnea. 1, 6, 7

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Address Modifiable Risk Factors BEFORE Considering Testosterone Therapy

Chronic alcohol use, hypertension, and likely obesity (implied by low testosterone and comorbidities) are reversible causes of secondary hypogonadism that MUST be addressed first. 1, 6, 7

Lifestyle Interventions

• Alcohol cessation or significant reduction is mandatory, as chronic alcohol use suppresses the hypothalamic-pituitary-gonadal axis and causes secondary hypogonadism. 1, 6
• Weight loss through a hypocaloric diet (500–750 kcal/day deficit) and regular exercise (≥150 minutes/week of moderate-intensity aerobic activity plus resistance training 2–3 times weekly) can reverse obesity-associated secondary hypogonadism and improve testosterone levels without medication. 1, 7
• Optimize blood pressure control and screen for metabolic syndrome (fasting glucose, HbA1c, lipid panel), as these conditions are strongly associated with hypogonadism. 1, 2, 6

Screen for Sleep Apnea

• Evaluate for obstructive sleep apnea (OSA), which is common in men with hypertension, obesity, and hypogonadism. 1, 5, 3
• Untreated severe OSA is an absolute contraindication to testosterone therapy per FDA labeling, as testosterone can worsen sleep apnea. 1, 5, 3

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If Hypogonadism is Confirmed and Symptomatic: Treatment Algorithm

Only proceed with testosterone therapy if ALL of the following criteria are met: 1, 3, 4

1. Two separate morning total testosterone measurements <300 ng/dL 1, 3
2. Specific symptoms of testosterone deficiency: diminished libido and erectile dysfunction (NOT fatigue, low energy, or mood complaints, which show minimal to no benefit from testosterone therapy) 1, 3, 8
3. Hematocrit <54% after addressing secondary causes of erythrocytosis 1, 5, 3
4. Total PSA <4.0 ng/mL and normal DRE 1, 5, 3
5. No active desire for fertility preservation 1, 3, 4
6. No recent cardiovascular events (myocardial infarction or stroke within 3–6 months) 1, 5, 3
7. No untreated severe obstructive sleep apnea 1, 5, 3

Preferred Formulation

• Transdermal testosterone gel 1.62% at 40.5 mg daily (2 pump actuations) is the preferred first-line formulation due to more stable day-to-day testosterone levels and markedly lower risk of erythrocytosis (15% vs. 44% with injectable testosterone). 1, 5
• Given his elevated hemoglobin, transdermal gel is strongly preferred over injectable testosterone to minimize erythrocytosis risk. 1, 5

Monitoring Requirements

• Testosterone levels at 2–3 months after initiation, targeting mid-normal range (500–600 ng/dL). 1, 3, 4
• Hematocrit at each visit—withhold treatment if >54% and consider phlebotomy in high-risk cases. 1, 5, 3
• PSA at 3–6 months, then annually; refer for urologic evaluation if PSA increases >1.0 ng/mL in the first 6 months or >0.4 ng/mL per year thereafter. 1, 3, 4
• Reassess symptoms at 12 months—discontinue testosterone if no improvement in sexual function, as this is the only domain with proven benefit (standardized mean difference 0.35). 1, 3, 8

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Critical Pitfalls to Avoid

• Do not diagnose hypogonadism on a single testosterone measurement, regardless of how low the value is. 1, 2, 3
• Do not initiate testosterone therapy without confirming the patient does not desire fertility, as testosterone causes prolonged and potentially irreversible azoospermia. 1, 3, 4
• Do not ignore elevated hemoglobin/hematocrit—this must be evaluated and corrected before considering testosterone therapy. 1, 5, 3
• Do not expect testosterone therapy to improve fatigue, energy, physical function, or mood—these domains show minimal to no benefit even in confirmed hypogonadism. 1, 3, 8
• Do not skip LH/FSH testing once low testosterone is confirmed, as the distinction between primary and secondary hypogonadism directs therapy and fertility counseling. 1, 2, 3