What laboratory tests should I order for a new patient who is currently on testosterone replacement therapy?

Laboratory Monitoring for a Patient Already on Testosterone Replacement Therapy

When assuming care of a patient already on testosterone therapy, order a baseline panel consisting of morning serum total testosterone, hemoglobin/hematocrit, prostate-specific antigen (PSA) for men over 40 years, and luteinizing hormone (LH) to establish current therapeutic levels, screen for polycythemia, evaluate prostate cancer risk, and differentiate primary versus secondary hypogonadism. 1

Essential Baseline Laboratory Tests

Testosterone Level Assessment

• Draw morning serum total testosterone between 8 AM and 10 AM to account for diurnal variation and confirm the current regimen achieves adequate hormone levels (target mid-to-upper normal range, approximately 264–916 ng/dL). 1
• If the patient is on injectable testosterone, timing matters: peak levels occur 2–5 days after injection, so interpret results based on the interval since the most recent dose. 2
• Consider measuring free or bioavailable testosterone if total testosterone is near the lower limit of normal or if the patient has conditions that alter sex hormone-binding globulin (SHBG), such as obesity or diabetes. 3

Hematologic Monitoring

• Measure baseline hemoglobin and hematocrit; if hematocrit exceeds 50%, investigate the cause before continuing therapy. 2, 1
• If hematocrit rises above 54% during treatment, reduce the testosterone dose or temporarily discontinue therapy to prevent treatment-related polycythemia. 1
• Injectable testosterone formulations carry the highest risk of erythrocytosis—men on 200 mg biweekly injections have an 8% risk of hematocrit exceeding 54% compared to 1% with 100 mg weekly. 4
• Consider therapeutic phlebotomy if hematocrit remains elevated despite dose reduction. 1

Prostate Cancer Screening

• Obtain PSA in all men over 40 years before continuing testosterone therapy to exclude occult prostate cancer. 2, 1
• Perform a digital rectal examination (DRE) at baseline to assess prostate morphology and detect abnormalities. 2
• If baseline PSA is elevated, repeat the measurement to rule out a spurious rise before proceeding. 1
• A PSA rise greater than 1.0 ng/mL during the first six months of treatment or more than 0.4 ng/mL per year thereafter warrants urologic referral for possible biopsy. 2

Hormonal Etiology Assessment

• Measure serum LH to distinguish primary from secondary hypogonadism and guide further endocrine work-up. 5, 1
• If LH is low or low-normal, obtain serum prolactin to screen for hyperprolactinemia; persistently elevated prolactin requires endocrinology referral. 2, 1
• Measure follicle-stimulating hormone (FSH) if fertility is a concern or future reproduction is planned; elevated FSH with low testosterone suggests primary testicular failure. 2, 1

Additional Tests Based on Clinical Presentation

Cardiovascular Risk Assessment

• Obtain a fasting lipid panel to inform ASCVD risk stratification, as testosterone deficiency is associated with adverse cardiovascular risk profiles. 2, 1

Gynecomastia or Breast Symptoms

• Measure serum estradiol only when the patient presents with breast symptoms or gynecomastia; an elevated level prompts endocrinology referral. 2, 1

Fertility Concerns

• Consider semen analysis for patients interested in preserving fertility, as exogenous testosterone suppresses spermatogenesis. 2, 1

Pituitary Pathology Screening

• Consider pituitary MRI for patients with total testosterone levels below 150 ng/dL combined with low or low-normal LH, regardless of prolactin levels, to rule out pituitary tumors. 2

Ongoing Monitoring Schedule

Initial Follow-Up (1–2 Months)

• Schedule the first follow-up visit 1–2 months after assuming care to evaluate clinical response and adjust the dose if testosterone levels remain subtherapeutic. 2, 1
• Repeat morning serum testosterone, hemoglobin/hematocrit, and PSA to verify therapeutic targets are met and safety parameters remain acceptable. 1

Routine Monitoring

• Conduct follow-up visits every 3–6 months during the first year, then annually thereafter if the patient remains stable. 1
• At each visit, re-measure morning serum testosterone, PSA, and hemoglobin/hematocrit to ensure continued efficacy and safety. 1
• Perform a digital rectal examination at each visit to monitor prostate health alongside PSA testing. 1
• Assess symptomatology including libido, erectile function, energy, mood, and lower urinary tract symptoms to gauge clinical benefit. 1

Critical Safety Thresholds

Polycythemia Management

• Never continue testosterone therapy without regular hematocrit monitoring, as omission can lead to undetected polycythemia. 1
• Injectable testosterone is associated with the greatest treatment-induced increases in hemoglobin/hematocrit. 2

Prostate Cancer Surveillance

• Never continue testosterone therapy without regular PSA monitoring, as omission can lead to occult prostate cancer progression. 1
• A PSA rise greater than 1.4 µg/L per year should trigger urological evaluation with possible reflex testing (e.g., 4K score, PHI) and consideration of prostate biopsy. 1

Fertility Counseling

• Counsel all patients of reproductive age that exogenous testosterone suppresses spermatogenesis; advise cessation of therapy well before planned conception attempts. 1

Sleep Apnea Screening

• Screen for sleep apnea history at baseline and monitor symptoms during therapy, as testosterone can exacerbate or precipitate obstructive sleep apnea, especially at higher doses. 1