Testosterone Replacement Therapy Monitoring

Introduction to Monitoring

• The American Urological Association recommends monitoring total testosterone levels, hemoglobin/hematocrit, PSA (in men over 40), and assessing cardiovascular risk factors to minimize risks and ensure treatment efficacy during testosterone replacement therapy 1

Laboratory Tests and Monitoring

• Testosterone levels should be checked 2-3 months after treatment initiation or dose change, and ongoing every 6-12 months once stable, with a target of mid-normal range (350-600 ng/dL) 1, 2, 3, 4
• Hemoglobin/hematocrit should be monitored 1-2 months after initiation, every 3-6 months during the first year, and then annually 3, 1, 5
• Lipid profiles should be monitored for cardiovascular risk assessment, as testosterone therapy may increase risk of cardiovascular events, particularly in patients with pre-existing risk factors 1
• PSA should be monitored according to standard prostate cancer screening guidelines, as recommended by The Journal of Urology guidelines 1
• Baseline laboratory tests, including total testosterone, free testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) should be performed to distinguish primary from secondary hypogonism, as recommended by the American Gastroenterological Association 2
• The risk of erythrocytosis varies by administration route, as shown in the following table:

3, 1

Adverse Effects and Their Management

• The most common adverse effect of testosterone therapy is polycythemia, with a risk that varies by administration route, and hematocrit should be monitored regularly, with therapy withheld if hematocrit exceeds 50% and intervention warranted if exceeds 54% 1
• Elevated hematocrit increases blood viscosity, potentially increasing risk of thromboembolic events, particularly in patients with pre-existing cardiovascular risk factors, as reported by the New England Journal of Medicine and The Journal of Urology 3, 6
• If two PSA levels raise suspicion for prostate cancer, reflex testing (4K or phi) or prostate biopsy with/without MRI should be considered, and therapy should be discontinued if prostate cancer is detected 1
• Temporarily discontinue testosterone therapy until hematocrit normalizes, and consider dose reduction when restarting therapy, as recommended by the American Urological Association and the New England Journal of Medicine 1, 3
• Consider therapeutic phlebotomy if clinically indicated, and recheck hematocrit within 1-2 months after intervention, as part of a comprehensive approach to managing elevated hematocrit, as recommended by the American Urological Association and the New England Journal of Medicine 1, 3

Best Practices for Therapy

• Commercially manufactured testosterone products should be prescribed rather than compounded testosterone due to variations in potency and quality 1
• Clinicians should be aware of potential drug interactions, such as androgens increasing sensitivity to oral anticoagulants, requiring dose adjustments 1
• Testosterone therapy should be evaluated for symptom improvement within 12 months, and discontinued if no improvement occurs, as recommended by the American College of Physicians 5
• 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, as recommended by The Journal of Urology guidelines and the American Urological Association 1
• Clinicians should carefully weigh potential benefits against risks, particularly cardiovascular and prostate concerns, as recommended by the American College of Physicians and the American College of Cardiology 3, 5
• Transdermal preparations may show variable absorption, and injectable testosterone may be associated with greater cardiovascular risk compared to gels due to fluctuating levels, as noted by the American Gastroenterological Association 2
• Testosterone therapy may suppress spermatogenesis and affect fertility, as reported by The Journal of Urology guidelines 1
• Prolactin is required when total testosterone is low with low/low-normal LH levels to screen for hyperprolactinemia 1
• Estradiol should be measured in patients presenting with breast symptoms or gynecomastia prior to TRT 1
• Follicle-Stimulating Hormone (FSH) assesses reproductive health status in men interested in preserving fertility, and consideration should be given to semen analysis if FSH is elevated, as recommended by The Journal of Urology guidelines 1
• Testicular Examination evaluates size, consistency, and descent in men interested in preserving fertility, as recommended by The Journal of Urology guidelines 1
• Genetic testing (karyotype and Y-chromosome analysis) should be considered for men with severe oligospermia or non-obstructive azoospermia, as recommended by The Journal of Urology guidelines 1