What is the typical workup for a male patient with suspected low testosterone (hypogonadism)?

Low Testosterone Workup

Confirm hypogonadism with two separate morning total testosterone measurements (drawn between 8-10 AM) showing levels below 300 ng/dL, then measure LH, FSH, and free testosterone to distinguish primary from secondary hypogonadism and guide treatment decisions. 1

Initial Diagnostic Testing

Morning Testosterone Measurements

• Draw two separate morning total testosterone levels between 8-10 AM to confirm persistent hypogonadism, as single measurements are insufficient due to assay variability and diurnal fluctuation 1, 2, 3
• Levels below 300 ng/dL establish hypogonadism, while levels above 350 ng/dL are likely normal 1, 4
• The "grey zone" between 300-350 ng/dL requires additional testing with free testosterone 4

Free Testosterone and SHBG

• Measure free testosterone by equilibrium dialysis in addition to total testosterone, especially in men with obesity, diabetes, or borderline total testosterone levels 1
• Obtain sex hormone-binding globulin (SHBG) levels to distinguish true hypogonadism from SHBG-related decreases in total testosterone 1
• This is critical because 26.3% of men over 60 years with erectile dysfunction have normal total testosterone but low free testosterone, representing symptomatic hypogonadism that would be missed by total testosterone screening alone 5

Distinguishing Primary from Secondary Hypogonadism

Gonadotropin Testing

• Measure serum LH and FSH after confirming low testosterone to determine the type of hypogonadism 1, 2
• Elevated LH/FSH with low testosterone indicates primary (testicular) hypogonadism, while low or low-normal LH/FSH with low testosterone indicates secondary (hypothalamic-pituitary) hypogonadism 1
• This distinction has critical treatment implications for fertility preservation and treatment selection 1

Additional Testing for Secondary Hypogonadism

• Measure serum prolactin in patients with low testosterone and low/normal LH levels to screen for hyperprolactinemia 2
• Consider pituitary MRI for patients with total testosterone below 150 ng/dL and low/normal LH regardless of prolactin levels 2
• Evaluate for reversible causes including sleep disorders, thyroid dysfunction, anemia, vitamin D deficiency, metabolic syndrome, and medications (opiates, corticosteroids) 1, 4

Pre-Treatment Assessment

Cardiovascular and Hematologic Evaluation

• Document baseline hematocrit or hemoglobin before initiating testosterone therapy to monitor for erythrocytosis during treatment, with hematocrit above 54% being an absolute contraindication 1, 2
• Assess all patients for cardiovascular disease risk factors, as recent cardiovascular events within the past 3-6 months warrant delaying initiation of therapy 1, 2

Prostate Assessment

• Perform digital rectal examination to assess for palpable prostate nodules or induration 1, 2
• Measure baseline PSA level in men over 40 years, with PSA above 4.0 ng/mL requiring urologic evaluation and documented negative prostate biopsy before initiating therapy 1

Fertility Evaluation

• Conduct reproductive health evaluation in men interested in fertility before treatment, as testosterone therapy causes azoospermia and is absolutely contraindicated in men seeking fertility preservation 1, 2
• For men with secondary hypogonadism desiring fertility, gonadotropin therapy (hCG plus FSH) is mandatory instead of testosterone 1

Additional Baseline Testing

• Measure serum estradiol in patients presenting with breast symptoms or gynecomastia prior to starting therapy 2
• Evaluate for sleep apnea by history taking, as untreated severe obstructive sleep apnea is a contraindication to testosterone therapy 1, 2

Common Pitfalls to Avoid

• Never diagnose hypogonadism based on symptoms alone without laboratory confirmation, as symptoms lack specificity 1, 2
• Never draw testosterone levels outside the 8-10 AM window, as this violates diagnostic standards and produces unreliable results 1, 3
• Never skip free testosterone measurement in men over 60 years, obese men, or those with diabetes, as elevated SHBG can mask true hypogonadism 1, 5
• Never attempt to diagnose the type of hypogonadism while the patient is on testosterone therapy, as exogenous testosterone suppresses gonadotropins and results will be misleading 1
• Never start testosterone without confirming the patient does not desire fertility, as this causes prolonged and potentially irreversible azoospermia 1, 2