What blood tests and frequency are recommended for a patient on testosterone (Testosterone) therapy?

Monitoring Blood Tests for Patients on Testosterone Therapy

Patients on testosterone therapy require baseline and ongoing monitoring of hemoglobin/hematocrit, PSA (in men over 40), and testosterone levels, with hematocrit being the most critical safety parameter requiring intervention if it exceeds 54%. 1

Baseline Testing (Before Starting Therapy)

Essential Pre-Treatment Labs

• Hemoglobin and hematocrit must be measured before initiating testosterone therapy; if hematocrit exceeds 50%, withhold therapy until the etiology is investigated 1
• PSA testing is required in all men over 40 years of age to exclude occult prostate cancer; if elevated, obtain a second PSA to rule out spurious elevation 1
• Serum estradiol should be measured in patients presenting with breast symptoms or gynecomastia prior to starting therapy 1
• Serum LH should be measured in all patients with confirmed low testosterone to establish whether hypogonadism is primary or secondary 2

Additional Baseline Assessments

• Cardiovascular risk factors including lipid profile, blood pressure, and assessment for diabetes must be evaluated, as these represent modifiable ASCVD risk factors 1
• Fertility evaluation including testicular exam and FSH measurement should be performed in men interested in preserving fertility 1

Monitoring During Treatment

Hematocrit/Hemoglobin - The Critical Safety Parameter

• Hematocrit >54% warrants immediate intervention such as dose reduction or temporary discontinuation of therapy 1
• Injectable testosterone formulations carry the highest risk of erythrocytosis (43.8% of patients had elevated hematocrit >52% in one study), compared to transdermal patches (15.4%) and gels (2.8-17.9% depending on dose) 1
• Most hematocrit changes occur within the first 3 months of therapy, making early monitoring particularly important 1
• The FDA label specifically mandates that hemoglobin and hematocrit be checked periodically in patients receiving long-term androgen administration 3

Clinical Pitfall: Erythrocytosis increases blood viscosity and can aggravate coronary, cerebrovascular, or peripheral vascular disease, particularly in elderly patients or those with chronic obstructive pulmonary disease 1. Research has documented strokes occurring in patients who developed significant hemoconcentration on testosterone therapy 4.

PSA Monitoring

• For patients over 40 who maintain on-treatment testosterone levels in the normal range, PSA testing frequency should follow a shared decision-making approach in accordance with AUA Early Detection of Prostate Cancer Guidelines 1
• The Endocrine Society recommends monitoring PSA in men over 40 during treatment 2

Testosterone Level Monitoring

• Target testosterone levels should be in the mid-normal range (350-750 ng/dL) during treatment 2
• Testosterone levels should be monitored to ensure therapeutic efficacy and avoid supraphysiologic levels, which are associated with higher rates of erythrocytosis 1

Other Monitoring Parameters

• Lipid profile monitoring is warranted, as testosterone therapy consistently decreases HDL-cholesterol and increases LDL-cholesterol 5, 6
• Serum estradiol should be measured if breast symptoms or gynecomastia develop during treatment 1, 2
• Liver function tests may show slight changes but are generally not clinically significant 5

Frequency of Monitoring

While the guidelines do not specify exact intervals, the evidence suggests:

• Most intensive monitoring should occur in the first 3-6 months, when hematocrit changes are most pronounced and prostate volume increases stabilize 1
• Hematocrit monitoring should be more frequent with injectable testosterone (every 3-6 months initially) given the 43.8% incidence of elevated values, compared to less frequent monitoring with transdermal preparations 1
• Periodic monitoring is required long-term per FDA labeling, with clinical judgment guiding frequency based on individual risk factors 3

Management of Abnormal Values

Elevated Hematocrit (>54%)

• Implement dose reduction, temporarily discontinue testosterone, perform therapeutic phlebotomy, or arrange blood donation 1
• Consider switching from injectable to transdermal formulations, which have lower erythrocytosis rates 1, 5

Elevated PSA

• Two elevated baseline PSA levels warrant formal evaluation including reflex testing (4K or phi) and consideration of prostate biopsy with/without MRI before continuing therapy 1

Critical Safety Note: Although no testosterone-associated thromboembolic events had been reported in the literature as of 2004, the theoretical risk remains significant given the documented increases in blood viscosity, particularly in patients with pre-existing cardiovascular disease 1.