What laboratory tests are used to diagnose hypogonadism (low testosterone)?

From the Guidelines

To diagnose hypogonadism, or low testosterone, clinicians should use a total testosterone level below 300 ng/dL as a reasonable cut-off, with measurements taken on two separate occasions in the early morning 1. The diagnosis of testosterone deficiency requires both a low testosterone measurement as well as the presence of select symptoms and/or signs.

• The primary lab test used is total testosterone, which should be measured in the morning when levels are highest.
• A normal range for adult males is typically 300-1000 ng/dL, with levels below 300 ng/dL generally considered low 1.
• If total testosterone is low, additional tests should include free testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) to determine if the cause is primary (testicular) or secondary (pituitary/hypothalamic) 1.
• Other helpful tests include complete blood count, comprehensive metabolic panel, prolactin levels, and thyroid function tests to rule out other conditions that might affect testosterone.
• For accurate results, testosterone should be measured on two separate occasions, preferably using the same laboratory with the same method/instrumentation for measurement 1.
• Clinicians should also conduct a targeted physical exam to examine patients for signs associated with low testosterone, including evaluation of general body habitus, virilization status, body mass index or waist circumference, gynecomastia, testicular evaluation, varicocele presence, and prostate size and morphology 1.
• Patient-reported symptoms associated with low testosterone, such as reduced energy, reduced endurance, diminished work and/or physical performance, fatigue, visual field changes, anosmia, depression, reduced motivation, poor concentration, impaired memory, irritability, infertility, reduced sex drive, and changes in erectile function, should also be noted 1.

From the FDA Drug Label

Prior to initiating Testosterone Gel, 1. 62%, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range.

The laboratory test used to diagnose hypogonadism (low testosterone) is serum testosterone concentration measurement, which should be done in the morning on at least two separate days.

• The diagnosis of hypogonadism is confirmed by ensuring that serum testosterone concentrations are below the normal range 2.

From the Research

Laboratory Tests for Diagnosing Hypogonadism

The diagnosis of hypogonadism is based on clinical signs and symptoms, as well as laboratory confirmation via the measurement of low morning testosterone levels on two different occasions 3. The following laboratory tests are used to diagnose hypogonadism:

• Measurement of morning total testosterone level by a reliable assay as the initial diagnostic test 4
• Repeating the measurement of morning total testosterone to confirm the diagnosis 4
• Measurement of free or bioavailable testosterone level using validated assays in some men in whom total testosterone is near the lower limit of normal or in whom SHBG abnormality is suspected 4
• Serum luteinizing hormone and follicle-stimulating hormone levels to distinguish between primary (hypergonadotropic) and secondary (hypogonadotropic) hypogonadism 3

Interpretation of Test Results

The interpretation of test results is as follows:

• Total testosterone levels of less than 8 nmol/l highly support a diagnosis of hypogonadism 5
• Levels greater than 12 nmol/l are likely to be normal 5
• The grey zone between 8 and 12 nmol/l requires further evaluation and assessment of free or non-sex hormone-binding globulin-bound (bioavailable) testosterone 5
• A trial period of testosterone treatment may be required to confirm the diagnosis 5

Additional Tests

Additional tests may be required in some cases, such as:

• Measurement of hematocrit for detection of polycythemia in men aged >50 years 3
• Digital rectal examination with a serum prostate-specific antigen level measurement for prostate cancer screening in men aged >50 years 3
• Serial measurement of bone mineral density during androgen therapy to confirm end-organ effects 3