What laboratory tests should be obtained prior to starting testosterone replacement therapy (TRT)?

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Laboratory Tests Required Before Starting Testosterone Replacement Therapy

Before initiating testosterone replacement therapy (TRT), several laboratory tests should be obtained to ensure patient safety and establish baseline values for monitoring. The following tests are recommended by clinical guidelines:

Essential Laboratory Tests

  • Total testosterone levels measured on at least two separate occasions in the morning (8-10 AM) to confirm testosterone deficiency 1
  • Luteinizing hormone (LH) to determine the etiology of testosterone deficiency (primary vs. secondary hypogonadism) 2
  • Hemoglobin/hematocrit as baseline measurement, with consideration to withhold therapy if hematocrit exceeds 50% 3, 2
  • Prostate-specific antigen (PSA) in men over 40 years of age to exclude occult prostate cancer 3, 2
  • Estradiol levels in patients who present with breast symptoms or gynecomastia prior to starting therapy 3, 2

Additional Tests Based on Clinical Presentation

  • Follicle-stimulating hormone (FSH) in men interested in preserving fertility to assess reproductive health status 3, 2
  • Prolactin levels in patients with low testosterone and low/normal LH to screen for hyperprolactinemia 2
  • Free testosterone (preferably by equilibrium dialysis) and sex hormone-binding globulin in patients who are obese or have conditions that alter sex hormone binding 1

Cardiovascular Risk Assessment

  • Assessment of cardiovascular disease risk factors including both fixed (age, gender) and modifiable factors (dyslipidemia, hypertension, diabetes, smoking) 3, 2
  • Lipid profile to establish baseline cardiovascular risk 2, 4
  • Fasting glucose or HbA1c to screen for diabetes 5

Special Considerations

  • Pituitary MRI should be considered in men with total testosterone levels <150 ng/dL combined with low/normal LH, regardless of prolactin levels 3, 2
  • Semen analysis in men with elevated FSH who are interested in fertility 3
  • Reproductive genetic testing (karyotype and Y-chromosome microdeletion analysis) in men with severe oligospermia or non-obstructive azoospermia 3

Common Pitfalls to Avoid

  • Failure to confirm low testosterone with repeat morning measurements can lead to inappropriate therapy 1
  • Overlooking secondary causes of hypogonadism by not measuring LH/FSH 2
  • Initiating therapy without baseline hematocrit may increase risk of polycythemia, especially with injectable formulations 3, 2
  • Not screening for prostate cancer in men over 40 before starting TRT 3, 4
  • Neglecting fertility concerns in men of reproductive age 3, 5

By obtaining these laboratory tests before initiating testosterone replacement therapy, clinicians can establish appropriate baselines, identify contraindications, and develop a tailored monitoring plan to optimize outcomes while minimizing potential risks.

References

Research

Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline.

The Journal of clinical endocrinology and metabolism, 2018

Guideline

Serum Testosterone Testing in Hormone Replacement Therapy (HRT)

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Testosterone Therapy Evaluation and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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