What is the diagnostic approach to male hypogonadism (testosterone deficiency)?

From the Guidelines

The diagnostic approach to male hypogonadism should begin with a thorough clinical assessment, followed by two morning total testosterone measurements on separate days, with a cut-off value of 300 ng/dL, as recommended by the American Urological Association guideline 1. The diagnosis of testosterone deficiency requires both a low testosterone measurement and the presence of select symptoms and/or signs.

• The clinical diagnosis of testosterone deficiency is only made when patients have low total testosterone levels combined with symptoms and/or signs, 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 1.
• Clinicians should consider measuring total testosterone in patients with a history of unexplained anemia, bone density loss, diabetes, exposure to chemotherapy, exposure to testicular radiation, HIV/AIDS, chronic narcotic use, male infertility, pituitary dysfunction, and chronic corticosteroid use, even in the absence of symptoms or signs associated with testosterone deficiency 1.
• A targeted physical exam should be conducted 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. The use of validated questionnaires is not currently recommended to either define which patients are candidates for testosterone therapy or monitor symptom response in patients on testosterone therapy 1. Additional testing may include luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, and sex hormone-binding globulin (SHBG) to distinguish between primary (testicular) and secondary (hypothalamic-pituitary) hypogonadism, as well as a complete blood count, comprehensive metabolic panel, hemoglobin A1c, and lipid panel to assess for comorbidities 1.
• If secondary hypogonadism is suspected, pituitary function tests and brain MRI may be necessary to evaluate for pituitary tumors or other central causes 1.
• Semen analysis should be considered in men concerned about fertility, and bone density testing may be warranted in men with prolonged hypogonadism due to increased fracture risk 1.
• Genetic testing (karyotype) should be considered in young men with primary hypogonadism to evaluate for conditions like Klinefelter syndrome 1.

From the FDA Drug Label

Prior to initiating testosterone gel 1.62%, confirm the diagnosis of hypogonadism by ensuring that serum testosterone has been measured in the morning on at least two separate days and that these concentrations are below the normal range.

The diagnostic approach to male hypogonadism (testosterone deficiency) involves measuring serum testosterone concentrations in the morning on at least two separate days to confirm that the levels are below the normal range 2. This is a crucial step before initiating treatment with testosterone gel 1.62%.

• Key steps:
  • Measure serum testosterone in the morning
  • Measure on at least two separate days
  • Confirm concentrations are below the normal range This approach helps establish a diagnosis of hypogonadism and ensures that treatment is necessary and appropriate 2 2.

From the Research

Diagnostic Approach to Male Hypogonadism

The diagnostic approach to male hypogonadism involves a combination of clinical evaluation and laboratory testing. The following steps are recommended:

• Assessing testosterone levels when an adult man exhibits signs of hypogonadism, such as low energy, fatigue, decreased sex drive, and decreased muscle mass and strength 3
• Measuring morning testosterone concentrations in serum on multiple occasions to confirm the diagnosis of hypogonadism 4
• Evaluating free testosterone or sex hormone-binding globulin levels in patients with clear symptoms and signs but normal-range total testosterone 5
• Considering other possible tests, such as semen analysis, pituitary imaging studies, genetic studies, bone densitometry, testicular ultrasonography, testicular biopsy, and specialized hormonal dynamic testing 5
• Estimating free testosterone levels to help diagnose hypogonadism 6
• Investigating causes of secondary hypogonadism, such as pituitary or hypothalamic disease 6

Laboratory Testing

Laboratory testing plays a crucial role in the diagnosis of male hypogonadism. The following factors should be considered:

• Analytical standardization of testosterone assays and harmonization of pre- and post-analytical laboratory practices 6
• Use of laboratory reference intervals provided to clinicians to interpret testosterone levels 6
• Sharing up-to-date and evidence-based action thresholds for serum testosterone with service users 6

Clinical Evaluation

A comprehensive clinical evaluation is essential to diagnose male hypogonadism. The following factors should be considered:

• Clinical signs and symptoms consistent with androgen deficiency, such as low energy, fatigue, decreased sex drive, and decreased muscle mass and strength 3, 4
• Medical history, including history of androgen therapy or infertility 5, 4
• Physical examination, including evaluation of testicular size and consistency 5