From the Guidelines
The diagnostic approach for hypogonadism should begin with a thorough clinical assessment, followed by laboratory testing, including morning total testosterone levels measured on two separate occasions, with a cut-off value of <300 ng/dL, as recommended by the American Urological Association guideline 1. 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.
Key Components of the Diagnostic Approach
- Morning total testosterone levels measured on two separate occasions, preferably between 8-10 AM when levels are highest 1
- A cut-off value of <300 ng/dL to support the diagnosis of low testosterone 1
- Assessment of symptoms and signs associated with low testosterone, such as reduced energy, reduced endurance, and diminished work and/or physical performance 1
- 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, and prostate size and morphology 1
Additional Testing
- Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels to distinguish between primary and secondary hypogonadism 1
- Prolactin and sex hormone-binding globulin (SHBG) levels to further evaluate the etiology of hypogonadism 1
- Complete blood count, comprehensive metabolic panel, thyroid function tests, and pituitary MRI if secondary hypogonadism is suspected 1
- Karyotype analysis to rule out Klinefelter syndrome in men with primary hypogonadism 1
- Semen analysis for men concerned about fertility 1
- Bone density testing for men with prolonged hypogonadism due to increased risk of osteoporosis 1
Recent Guidelines
The 2021 Standards of Medical Care in Diabetes recommend considering screening with a morning serum testosterone level in men with diabetes who have symptoms or signs of hypogonadism, such as decreased sexual desire or activity, or erectile dysfunction 1. The American Urological Association guideline recommends 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.
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 diagnostic approach for hypogonadism 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:
- Measure serum testosterone concentrations
- Take measurements in the morning
- Measure on at least two separate days
- Confirm levels are below the normal range
- This approach is used to confirm the diagnosis of hypogonadism before initiating treatment with testosterone gel, 1.62% 2 2.
From the Research
Diagnostic Approach for Hypogonadism
The diagnostic approach for hypogonadism involves several steps, including:
- Establishing the presence of symptoms/signs of testosterone deficiency 3
- Considering other potential causes of manifestations and excluding conditions that transiently suppress testosterone 3
- Measuring fasting serum total testosterone in the morning on at least 2 separate days, or free testosterone by equilibrium dialysis or calculated free testosterone in men with conditions that alter sex hormone-binding globulin or serum total testosterone near lower limit of normal 3
- Measuring serum luteinizing hormone and follicle-stimulating hormone levels to distinguish between primary (hypergonadotropic) and secondary (hypogonadotropic) hypogonadism 4
Laboratory Confirmation
Laboratory confirmation of hypogonadism is based on low morning testosterone levels on two different occasions 4.
- Measurement of luteinizing hormone and follicle-stimulating hormone levels is essential to establish whether the hypogonadism is primary or secondary 5
- In secondary hypogonadism, measurement of prolactin is always necessary, and measurement of other pituitary hormones, along with pituitary imaging, may be indicated 5
- Checking thyroid function may also be enlightening, and can raise additional therapeutic considerations 5
Evaluation and Management
Further evaluation is performed to identify the specific cause of hypogonadism and whether it is potentially reversible or an irreversible pathologic disorder 3.
- Assessment of clinical responses and measurement of serum testosterone levels generally suffice to confirm an adequate replacement dosage 4
- Serial measurement of bone mineral density during androgen therapy might be helpful to confirm end-organ effects 4
- For men aged >50 years, measurement of hematocrit for detection of polycythemia and a digital rectal examination with a serum prostate-specific antigen level measurement for prostate cancer screening during the first few months of androgen therapy is recommended 4