What laboratory tests should be obtained before initiating testosterone replacement therapy?

Laboratory Tests Before Starting Testosterone Replacement Therapy

Before initiating testosterone replacement therapy, you must obtain baseline morning total testosterone levels (measured on at least two separate occasions), hemoglobin/hematocrit, PSA (in men over 40), and LH levels to establish the diagnosis and screen for contraindications. 1, 2

Essential Core Laboratory Tests

Testosterone Confirmation

• Measure fasting morning total testosterone levels on at least two separate occasions to confirm testosterone deficiency, as single measurements are unreliable due to significant intra-individual variability 1, 3
• Timing is critical: obtain samples between 7:00 AM and 12:00 PM to account for diurnal variation, though compliance with this recommendation is notably poor in clinical practice 4, 5
• If total testosterone is near the lower limit of normal, obtain a free testosterone concentration using equilibrium dialysis or calculate it using an accurate formula 3

Luteinizing Hormone (LH)

• Measure serum LH to distinguish primary (testicular) from secondary (hypothalamic-pituitary) hypogonadism, which fundamentally guides treatment approach and identifies underlying etiology 1, 2

Hematologic Screening

• Measure baseline hemoglobin/hematocrit before starting therapy 6, 1, 2
• Withhold testosterone therapy if hematocrit exceeds 50% until the cause is investigated, as this represents an absolute contraindication 1, 7, 3
• Injectable testosterone formulations carry the greatest risk of treatment-induced polycythemia 1, 2

Prostate Screening (Age-Dependent)

• Measure PSA in men over 40 years of age to exclude occult prostate cancer before initiating therapy 6, 1
• Perform digital rectal examination at baseline 6
• Perform prostate biopsy if PSA exceeds 4.0 ng/mL or if digital rectal examination is abnormal before starting therapy 6
• PSA >3 ng/mL in African American men or those with first-degree relatives with prostate cancer warrants urological evaluation before therapy 3

Additional Tests Based on Clinical Presentation

Prolactin

• Measure serum prolactin in patients with low testosterone combined with low or low-normal LH levels to screen for hyperprolactinemia and potential pituitary tumors 1, 2

Pituitary Imaging

• Consider pituitary MRI for patients with total testosterone <150 ng/dL combined with low or low-normal LH, regardless of prolactin levels, to rule out non-secreting pituitary adenomas 1, 2

Fertility Assessment (If Relevant)

• Measure follicle-stimulating hormone (FSH) in men interested in preserving fertility to assess reproductive health status 1, 2
• Consider semen analysis for comprehensive fertility evaluation 1, 2
• Counsel patients that testosterone therapy suppresses spermatogenesis through negative feedback on pituitary gonadotropins, and recovery typically requires 6 months or longer after cessation 8, 2

Estradiol

• Measure estradiol in patients presenting with breast symptoms or gynecomastia prior to starting therapy 1, 2

Cardiovascular Risk Assessment

• Evaluate cardiovascular risk factors including lipid profile, particularly in patients with modifiable risk factors such as dyslipidemia, hypertension, diabetes, or smoking 1, 2, 7

Critical Contraindications to Screen For

The following represent absolute contraindications that must be excluded before initiating therapy:

• Breast or prostate cancer 7, 3
• Hematocrit ≥55% (or >50% per some guidelines) 7, 3
• Untreated severe obstructive sleep apnea 3
• Severe lower urinary tract symptoms 3
• Uncontrolled heart failure 3
• Myocardial infarction or stroke within the last 6 months 3
• Thrombophilia 3
• Planning fertility in the near term 3

Common Pitfalls to Avoid

• Only 9% of practitioners obtain testosterone levels during the recommended morning timeframe (7 AM-12 PM), leading to potentially inaccurate diagnoses 4
• Do not diagnose hypogonadism based on a single testosterone measurement, as significant intra-individual variability exists 3, 5
• Do not start therapy without confirming both biochemical androgen deficiency and consistent clinical symptoms 3
• Recognize that men with equivocal testosterone concentrations (7.0-12.5 nmol/L) require at least one additional measurement 5
• Obtain baseline voiding history using a standardized questionnaire and assess for sleep apnea history before initiating therapy 6