From the Guidelines
The diagnostic workup for hypogonadism should begin with two total testosterone measurements taken on separate occasions in the early morning, with a cut-off value of 300 ng/dL, and should be combined with a thorough clinical assessment of symptoms and signs. This approach is supported by the American Urological Association guideline, which recommends using a total testosterone level below 300 ng/dL as a reasonable cut-off in support of the diagnosis of low testosterone 1. The guideline also emphasizes the importance of 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.
The clinical diagnosis of testosterone deficiency requires both a low testosterone measurement and the presence of select 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. A targeted physical exam should also 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.
Additional tests, such as luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, and sex hormone-binding globulin (SHBG), may be ordered to determine if the cause is primary (testicular) or secondary (pituitary/hypothalamic) 1. However, 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.
Some key points to consider in the diagnostic workup include:
- Measuring total testosterone levels in the morning, when levels are highest, and on two separate occasions to account for fluctuations 1
- Assessing symptoms and signs associated with low testosterone, such as reduced energy and libido 1
- Conducting a targeted physical exam to evaluate for signs of low testosterone, such as gynecomastia and testicular atrophy 1
- Ordering additional tests, such as LH and FSH, to determine the underlying cause of low testosterone 1
- Ruling out other conditions that may be contributing to symptoms, such as sleep apnea and medication side effects 1.
It is essential to note that the evidence for the diagnostic workup of hypogonadism is based on guidelines and studies that prioritize the clinical assessment and laboratory testing, and the use of a comprehensive approach to identify the underlying cause of low testosterone 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 workup for hypogonadism (low testosterone) 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.
From the Research
Diagnostic Workup for Hypogonadism
The diagnostic workup for hypogonadism, also known as low testosterone, involves a combination of clinical evaluation, laboratory tests, and physical examination. The following steps are involved in the diagnostic workup:
- A detailed medical history and physical examination to identify symptoms and signs of hypogonadism, such as lethargy, fatigue, decreased sense of well-being, reduced physical and mental activity, diminished libido, and erectile dysfunction 3, 4
- Laboratory tests to measure total testosterone levels, with levels <200 ng/dl indicating hypogonadism 3
- Measurement of free testosterone levels, either by laboratory methods or calculation of free testosterone index, in cases where total testosterone levels are between 200 and 400 ng/dl 3
- Evaluation of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels to distinguish between primary and secondary hypogonadism 5, 6
- Assessment of prostate-specific antigen (PSA), hemoglobin, and hematocrit levels to exclude contraindications for androgen therapy and to monitor for potential side effects 3, 5
Clinical Symptoms and Questionnaires
Clinical symptoms of hypogonadism can vary depending on the age of onset, severity, and duration of the deficiency. Common symptoms include:
- Decreased sexual desire and activity
- Erectile dysfunction
- Low energy and mood swings
- Reduced muscle and bone mass
- Osteoporosis
- Mild anemia Questionnaires may be useful in identifying men who suffer from hypogonadism, but are not useful in screening for the condition 3, 5
Biochemical Evaluation
Biochemical evaluation involves measuring total and free testosterone levels, as well as LH and FSH levels. The following biochemical criteria are used to diagnose hypogonadism:
- Total testosterone levels <8 nmol/l highly support a diagnosis of hypogonadism
- Levels between 8 and 12 nmol/l require further evaluation and assessment of free or bioavailable testosterone
- Levels >12 nmol/l are likely to be normal 4