From the Guidelines
To diagnose hypogonadism, clinicians should use a total testosterone level below 300 ng/dL as a reasonable cut-off in support of the diagnosis, and this diagnosis should be made only after two total testosterone measurements are taken on separate occasions in an early morning fashion. This approach is based on the strongest and most recent evidence from the American Urological Association guideline 1.
When evaluating a patient for hypogonadism, it is essential to start with a thorough clinical evaluation, including a detailed medical history and physical examination. The diagnosis of testosterone deficiency requires both a low testosterone measurement and the presence of select symptoms and/or signs. Clinicians should make note of any 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.
In addition to clinical evaluation, laboratory testing is crucial. Morning total testosterone levels should be ordered on two separate occasions, as levels fluctuate throughout the day. If total testosterone is low (typically below 300 ng/dL), further tests such as free testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, and a complete metabolic panel should be considered. Additional tests may include thyroid function tests, complete blood count, and hemoglobin A1c. For men with low testosterone and low or normal LH/FSH, consider pituitary imaging to rule out pituitary disorders. Bone density testing may be warranted in cases of long-standing deficiency.
It is also important to consider the patient's medical history, as certain conditions such as 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 may increase the risk of low testosterone 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. Instead, a comprehensive clinical evaluation and laboratory testing should guide the diagnosis and treatment of hypogonadism.
Addressing underlying causes such as obesity, medication side effects, or chronic diseases is essential before considering testosterone replacement therapy. This comprehensive approach helps distinguish between primary hypogonadism (testicular failure) and secondary hypogonadism (hypothalamic-pituitary disorders), which guides appropriate treatment strategies.
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 approach to diagnosing 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.
- Key steps:
From the Research
Diagnosis of Hypogonadism
The approach to diagnosing hypogonadism, or testosterone deficiency, involves a combination of clinical evaluation and biochemical assessment of serum testosterone levels 3. The diagnosis should only be made in men with definite signs and symptoms, accompanied by low total testosterone levels measured in the morning by a reliable assay 4.
Clinical Evaluation
Clinical evaluation includes a detailed medical history and physical examination to identify symptoms of hypogonadism, such as:
- Low energy and fatigue
- Decreased sex drive and performance
- Decreased muscle mass and strength
- Decreased bone mineral density
- Increased body fat, particularly abdominal fat 5
- Loss of androgen-dependent functions, such as reduction in muscle mass, a shift in body composition towards more adipose tissue, decreased sexual function with diminished libido, depressed mood, loss of psychological energy, osteoporosis, and several other possible symptoms 3
Biochemical Assessment
Biochemical assessment involves measuring serum testosterone levels, with total testosterone levels of less than 8 nmol/l highly supporting a diagnosis of hypogonadism, and levels greater than 12 nmol/l likely to be normal 3. 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.
Diagnostic Criteria
The diagnosis of hypogonadism can be made based on the following criteria:
- Symptoms consistent with testosterone deficiency
- Low serum testosterone levels, defined as a total testosterone level < 300 ng/dL 5
- Biochemical evidence of testosterone deficiency, such as low free testosterone or bioavailable testosterone levels 3
Screening and Monitoring
Screening for hypogonadism is recommended in men starting at age 40 to 50 years, to establish a baseline testosterone level 5. Men receiving testosterone replacement therapy should be monitored for symptom improvement, potential adverse effects, and adherence, with serum testosterone, hematocrit, and prostate-specific antigen levels measured at baseline and at least annually in men 40 years or older 6.