How do you diagnose primary hypogonadism in patients with low testosterone (T) levels?

Diagnosing Primary Hypogonadism in Patients with Low Testosterone

Primary hypogonadism is diagnosed when you confirm low testosterone levels on two separate early morning measurements (total testosterone <300 ng/dL) combined with clinical symptoms, AND find elevated luteinizing hormone (LH) levels, which distinguishes testicular failure from pituitary/hypothalamic dysfunction. 1

Step 1: Confirm Low Testosterone

• Obtain two separate early morning total testosterone measurements (between 8-10 AM), ideally using the same laboratory and methodology 1
• Use total testosterone <300 ng/dL as the diagnostic threshold for low testosterone 1
• In obese patients, also measure free testosterone by equilibrium dialysis and sex hormone-binding globulin (SHBG), as obesity can lower SHBG and create falsely low total testosterone despite normal free testosterone 1
• Never diagnose based on a single measurement due to normal diurnal variation and assay variability 1

Step 2: Document Clinical Symptoms and Signs

Required symptoms (at least one must be present) 1:

• Reduced libido or erectile dysfunction
• Decreased energy, endurance, or work performance
• Persistent fatigue
• Reduced muscle mass or increased body fat
• Gynecomastia
• Depression, reduced motivation, poor concentration, or irritability
• Male infertility

Physical examination findings to document 1:

• Small or soft testes (suggests primary hypogonadism)
• Reduced body hair in androgen-dependent areas
• Increased BMI or waist circumference
• Gynecomastia
• Presence of varicocele

Step 3: Measure LH to Distinguish Primary from Secondary Hypogonadism

This is the critical step that defines primary hypogonadism:

• Measure serum LH in all patients with confirmed low testosterone 1
• Elevated LH (or high-normal LH) with low testosterone = PRIMARY hypogonadism (testicular failure with intact pituitary feedback) 1, 2
• Low or low-normal LH with low testosterone = SECONDARY hypogonadism (pituitary/hypothalamic dysfunction) 1

The European Association of Urology (2025) emphasizes that this classification is critical because primary hypogonadism patients can only receive testosterone therapy (which suppresses fertility), while secondary hypogonadism patients can potentially achieve both fertility and normal testosterone with gonadotropin therapy 1

Step 4: Additional Testing for Primary Hypogonadism

Once elevated LH confirms primary hypogonadism:

• Measure follicle-stimulating hormone (FSH) to assess spermatogenesis function 1
• Karyotype testing if Klinefelter syndrome is suspected (small firm testes, tall stature, gynecomastia) 2, 3
• Testicular ultrasound if masses, asymmetry, or structural abnormalities are detected on examination 1

Common Pitfalls to Avoid

• Do not rely on screening questionnaires for diagnosis—they lack specificity and should not replace clinical evaluation and laboratory testing 1
• Do not measure testosterone at random times due to normal diurnal variation; always use early morning samples 1
• Do not overlook free testosterone in obese patients, as low SHBG can create misleading total testosterone values 1
• Do not test during acute illness, as this can temporarily suppress testosterone levels 1
• Do not skip LH measurement—this is the only way to definitively distinguish primary from secondary hypogonadism and guide appropriate treatment 1

High-Risk Populations Requiring Screening

Even without symptoms, measure testosterone in patients with 1, 4:

• Unexplained anemia
• Bone density loss or osteoporosis
• Diabetes mellitus
• History of chemotherapy or testicular radiation
• HIV/AIDS
• Chronic narcotic or corticosteroid use
• Male infertility
• Pituitary dysfunction