What laboratory tests are indicated to consider for a patient who may require testosterone replacement therapy (TRT)?

From the Guidelines

To determine if a patient needs testosterone replacement therapy, a morning total testosterone level should be measured, and if levels are close to the lower limit, free testosterone concentrations should be determined, either directly or by calculations using total testosterone, sex hormone-binding globulin, and albumin concentrations 1. When evaluating a patient for potential testosterone replacement therapy, it is essential to consider the most recent and highest quality evidence. The 2024 standards of care in diabetes emphasize the importance of measuring morning total testosterone levels in men with symptoms or signs of low testosterone, using an accurate and reliable assay 1.

Key Laboratory Tests

• Morning total testosterone level, ideally drawn between 8-10 AM when levels are highest
• Free testosterone concentrations, either directly from equilibrium dialysis assays or by calculations using total testosterone, sex hormone-binding globulin, and albumin concentrations
• Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels to further evaluate the individual
• Complete blood count, comprehensive metabolic panel, lipid profile, and prostate-specific antigen (PSA) for men over 40 to establish baseline values and rule out contraindications to therapy
• Hemoglobin A1c, as diabetes can affect testosterone levels
• Thyroid function tests (TSH, free T4), since thyroid disorders can mimic hypogonadal symptoms

Clinical Considerations

• Testosterone replacement should only be initiated when clinical symptoms of hypogonadism are present alongside confirmed low testosterone levels
• Therapy carries risks, including erythrocytosis, sleep apnea exacerbation, and potential cardiovascular effects
• The diagnosis of low testosterone should be made only after two total testosterone measurements are taken on separate occasions, with both conducted in an early morning fashion 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

From the FDA Drug Label

Hemoglobin and hematocrit levels (to detect polycythemia) should be checked periodically in patients receiving long-term androgen administration. Serum cholesterol may increase during androgen therapy. Women with disseminated breast carcinoma should have frequent determination of urine and serum calcium levels during the course of androgen therapy Periodic (every six months) X-ray examinations of bone age should be made during treatment of pre-pubertal males to determine the rate of bone maturation and the effects of androgen therapy on the epiphyseal centers Hemoglobin and hematocrit should be checked periodically for polycythemia in patients who are receiving high doses of androgens.

The laboratory tests indicated to consider for a patient who may require testosterone replacement therapy (TRT) are:

• Hemoglobin and hematocrit levels to detect polycythemia
• Serum cholesterol to monitor for potential increases during androgen therapy
• Urine and serum calcium levels in women with disseminated breast carcinoma
• X-ray examinations of bone age every six months in pre-pubertal males to monitor bone maturation and the effects of androgen therapy on the epiphyseal centers 2 3

From the Research

Laboratory Tests for Testosterone Replacement Therapy (TRT)

To determine if a patient requires testosterone replacement therapy (TRT), several laboratory tests are indicated. The following tests are recommended:

• Morning total testosterone level by a reliable assay as the initial diagnostic test 4, 5
• Confirmation of the diagnosis by repeating the measurement of morning total testosterone 4, 5
• 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, 5
• Prostate-specific antigen (PSA) test to rule out prostate cancer 4, 5
• Hematocrit test to rule out erythrocytosis (hematocrit > 50%) 4, 5
• International Prostate Symptom Score (IPSS) to assess lower urinary tract symptoms 4, 5

Special Considerations

In certain patient populations, additional laboratory tests may be necessary. For example:

• In patients with end-stage renal disease (ESRD), testosterone replacement therapy can be considered in those with low bone mass and total testosterone level <200 ng/dl, or in younger patients with sexual complaints with total testosterone level lower than the reference range 6
• In patients with hypogonadism, early morning serum testosterone levels should be obtained to ensure accurate diagnosis 7

Current Guidelines

Current guidelines for the evaluation and management of testosterone deficiency (TD) recommend a comprehensive approach, including laboratory tests, physical examination, and medical history 8. The guidelines emphasize the importance of confirming the diagnosis of TD and ruling out other underlying conditions before initiating testosterone replacement therapy.