What labs are required prior to initiating Testosterone Replacement Therapy (TRT)?

Required Laboratory Tests Prior to Initiating Testosterone Replacement Therapy (TRT)

Prior to initiating testosterone replacement therapy, clinicians must measure total testosterone, luteinizing hormone, hemoglobin/hematocrit, and PSA (in men over 40), along with assessment of cardiovascular risk factors to establish baseline values and minimize risks. 1, 2

Essential Pre-TRT Laboratory Evaluation

Mandatory Tests for All Patients:

• Total Testosterone: Confirms diagnosis of testosterone deficiency 1
• Luteinizing Hormone (LH): Helps establish etiology of testosterone deficiency (primary vs. secondary hypogonadism) 1, 2
• Hemoglobin/Hematocrit: Baseline measurement to monitor for polycythemia; therapy should be withheld if hematocrit exceeds 50% 1, 2
• Cardiovascular Risk Assessment: Evaluate for both fixed (age, male gender) and modifiable risk factors (dyslipidemia, hypertension, diabetes, smoking) 1, 2

Conditional Tests Based on Clinical Presentation:

• Prolactin: Required when total testosterone is low with low/low-normal LH levels to screen for hyperprolactinemia 1

  • If elevated, repeat to confirm
  • Persistently elevated levels warrant endocrinology referral
  • Consider pituitary MRI if total testosterone <150 ng/dL with low/low-normal LH regardless of prolactin levels

• Estradiol: Measure in patients presenting with breast symptoms or gynecomastia prior to TRT 1

  • Elevated baseline estradiol requires endocrinology referral

• PSA: Required for men over 40 years 2

  • If elevated, obtain a second test to rule out spurious elevation
  • Consider reflex testing (4K or phi) and prostate biopsy with/without MRI if two PSA levels raise suspicion for prostate cancer

Fertility Evaluation (When Applicable):

For men interested in preserving fertility:

• Follicle-Stimulating Hormone (FSH): Assess reproductive health status 1, 2
• Testicular Examination: Evaluate size, consistency, and descent 1, 2
• Consider Semen Analysis: Particularly if FSH is elevated 1, 2
• Genetic Testing: Karyotype and Y-chromosome analysis for men with severe oligospermia or non-obstructive azoospermia 1, 2

Clinical Pitfalls and Important Considerations:

• Polycythemia Risk: Injectable testosterone carries the highest risk (43.8%) compared to transdermal patches (15.4%) and gels (2.8-17.9%) 2

• Venous Thromboembolism: Monitor for signs/symptoms of DVT or PE, as testosterone products have been associated with VTE 3

• Cardiovascular Risk: Some studies show increased risk of myocardial infarction and stroke with TRT 3

• Fertility Impact: Exogenous testosterone administration may lead to azoospermia 3

• Sleep Apnea: Consider risk in predisposed patients 3

• Prostate Monitoring: Regular monitoring of PSA is essential, especially in men over 40 2

Follow-up Laboratory Monitoring:

• Testosterone levels: 2-3 months after initiation and after dose changes 2
• Hemoglobin/hematocrit: 1-2 months after initiation, every 3-6 months during first year, then annually 2
• If hematocrit exceeds 54% while on therapy, intervention is warranted (dose reduction or temporary discontinuation) 1

By following this comprehensive laboratory assessment protocol before initiating TRT, clinicians can minimize risks and optimize outcomes for patients with testosterone deficiency, ultimately improving quality of life while monitoring for potential adverse effects.