In a 54‑year‑old man with known prostate cancer, PSA 3.9 ng/mL, markedly elevated total and free testosterone with suppressed FSH and LH, what is the most likely explanation and how should it be managed?

Exogenous Testosterone Use in Prostate Cancer Patient

This patient is almost certainly using exogenous testosterone supplementation, which is absolutely contraindicated in prostate cancer and must be stopped immediately. The markedly elevated total testosterone (2628 ng/dL, normal ~300-1000) and free testosterone (1231.3 pg/mL) with completely suppressed FSH (<0.7) and LH (<0.2) is the classic biochemical signature of exogenous androgen administration, not endogenous production. 1, 2

Diagnostic Confirmation

The suppressed gonadotropins (FSH and LH) definitively rule out endogenous testosterone production from testicular or adrenal sources, which would elevate—not suppress—these hormones through normal feedback mechanisms. 1, 2

• When testosterone levels are physiologically elevated, the hypothalamic-pituitary axis responds by increasing LH and FSH, not suppressing them to undetectable levels 1
• The only plausible explanation for supraphysiologic testosterone with undetectable gonadotropins is exogenous testosterone administration (injections, gels, patches, or pellets) 3, 1
• Alternative diagnoses like testosterone-secreting tumors would show elevated LH/FSH or at least detectable levels, not complete suppression 1

Immediate Management Actions

Discontinue all exogenous testosterone immediately and counsel the patient that testosterone supplementation directly stimulates prostate cancer growth and is absolutely contraindicated. 3, 1

Critical Steps:

• Conduct a direct, non-judgmental conversation to identify the source of testosterone (prescribed by another provider, obtained online, or through other means) and ensure complete cessation 3
• Verify testosterone levels fall to normal or castrate range within 2-4 weeks for short-acting preparations (gels, injections) or 3-6 months for long-acting pellets 3, 1
• Measure repeat PSA in 4-6 weeks after testosterone discontinuation, as the PSA of 3.9 ng/mL may be artificially suppressed or elevated by the exogenous androgens 3, 1

Prostate Cancer Reassessment

Once testosterone normalizes, perform comprehensive restaging to assess disease status, as exogenous testosterone may have stimulated cancer progression. 3, 1

• Obtain baseline imaging (bone scan and CT or MRI of abdomen/pelvis) to evaluate for metastatic disease, particularly if PSA rises after testosterone withdrawal 3, 4
• Consider prostate biopsy if PSA remains elevated (>4.0 ng/mL) or rises substantially after testosterone clearance, as disease may have progressed during androgen exposure 3
• Digital rectal examination should be performed to assess for local progression 3

Treatment Considerations Based on Disease Status

If disease remains localized: Continue active surveillance or definitive local therapy (surgery/radiation) as clinically appropriate based on Gleason score, PSA kinetics, and patient factors 3

If metastatic disease is discovered: Initiate androgen deprivation therapy (ADT) with LHRH agonist/antagonist plus novel hormonal agent (abiraterone or enzalutamide) for metastatic hormone-sensitive prostate cancer 3, 4

Critical Pitfall to Avoid

Never assume the patient will voluntarily disclose testosterone use without direct questioning. Many patients do not recognize testosterone as a "medication" or may obtain it through non-medical channels and fear judgment. 3

• Ask specifically: "Are you using any testosterone products—injections, gels, creams, patches, or pellets—prescribed by any doctor or obtained elsewhere?" 3
• Explain that testosterone "feeds" prostate cancer cells and that continued use could be life-threatening 3, 1
• Document the conversation and the patient's agreement to discontinue all testosterone products 3

Monitoring After Testosterone Discontinuation

Follow testosterone levels every 2-4 weeks until normalization, then monitor PSA every 3 months for the first year. 3, 1

• Testosterone should fall to <300 ng/dL (normal range) within 4-8 weeks for most preparations 3
• PSA trajectory after testosterone clearance provides critical prognostic information about disease activity 3, 5
• If PSA velocity exceeds 0.75 ng/mL/year or absolute PSA rises above 4.0 ng/mL, proceed with prostate biopsy and staging imaging 3