What laboratory tests are required before initiating testosterone replacement therapy?

Laboratory Tests Required Before Starting Testosterone Replacement Therapy

Before initiating testosterone replacement therapy, clinicians should measure morning total testosterone levels on at least two separate occasions, PSA (in men over 40), hemoglobin/hematocrit, and luteinizing hormone levels. 1, 2

Essential Baseline Laboratory Tests

• Total testosterone: Measure morning levels (between 8-10 AM) on at least two separate occasions to confirm testosterone deficiency 1
• Luteinizing hormone (LH): Helps establish the etiology of testosterone deficiency (primary vs. secondary hypogonadism) 2
• Hemoglobin/hematocrit: Baseline measurement to monitor for polycythemia; withhold therapy if hematocrit exceeds 50% 2, 3
• Prostate-specific antigen (PSA): Required in men over 40 years of age to exclude occult prostate cancer 2, 3

Additional Tests Based on Clinical Presentation

• Serum prolactin: Measure in patients with low testosterone combined with low or low/normal LH levels to screen for hyperprolactinemia 2
• Follicle-stimulating hormone (FSH): Recommended for men interested in preserving fertility to assess reproductive health status 2
• Estradiol: Should be measured in patients who present with breast symptoms or gynecomastia prior to starting therapy 2
• Lipid profile: Optional but recommended to assess cardiovascular risk factors 2, 4

Special Considerations

• Pituitary MRI: Consider for patients with total testosterone levels <150 ng/dL combined with low or low/normal LH, regardless of prolactin levels, to rule out pituitary tumors 2
• Semen analysis: Consider for patients interested in preserving fertility 2
• Assessment of cardiovascular disease risk factors: Evaluate both fixed (e.g., older age) and modifiable (e.g., dyslipidemia, hypertension, diabetes, smoking) risk factors 2, 4

Monitoring Algorithm During Treatment

1. First follow-up visit: Schedule 1-2 months after initiation to assess efficacy 2
2. Subsequent monitoring: Every 3-6 months during the first year, then yearly thereafter 2
3. At each follow-up visit:
   • Measure serum testosterone levels 2
   • Check hemoglobin/hematocrit (discontinue or reduce dose if hematocrit rises above reference range) 2, 3
   • Monitor PSA levels 2
   • Perform digital rectal examination 2
   • Assess symptomatic response to treatment 2

Pitfalls and Caveats

• Timing of blood tests: For men receiving injection therapy, interpret results based on the interval since the most recent injection (peak levels occur 2-5 days after injection) 2
• PSA monitoring: Consider urologic referral for possible biopsy for patients with an increase in PSA of more than 1.0 ng/mL during the first six months of treatment or more than 0.4 ng/mL per year thereafter 2
• Fertility concerns: Testosterone replacement therapy significantly reduces fertility; counsel patients accordingly 2
• Polycythemia risk: Injectable testosterone is associated with the greatest treatment-induced increases in hemoglobin/hematocrit 2

By following this comprehensive laboratory assessment before initiating testosterone replacement therapy, clinicians can minimize risks and optimize outcomes for patients with testosterone deficiency.