When to Stop

• Polycythemia → thromboembolic risk (DVT, PE, stroke). Phlebotomy or blood donation if Hct >54% per Endocrine Society. TRAVERSE found increased PE at clinical TRT dose.
• Atrial fibrillation — TRAVERSE 2023 signal (HR 1.46 vs placebo).
• Acute kidney injury — TRAVERSE 2023 signal.
• Cardiomyopathy / LVH at chronic supraphysiologic exposure (years).
• Permanent fertility loss — reported even after PCT in some cases. Risk highest with longer cycles, higher doses, age >35, low baseline FSH. Younger users are NOT protected — multiple case reports of permanent oligospermia after a single heavy cycle in age 20-30 men.
• Prostate hypertrophy / unmasking subclinical prostate cancer — TRT does not cause prostate cancer per current evidence but can accelerate clinically silent disease. PSA monitoring annually if >40 or family history.
• Sterile abscess at injection site — poor technique / contaminated UGL gear.
• Hepatic effects — minimal with injectables; significant with oral 17αAA (methyltestosterone, stanozolol). Oral T undecanoate (Jatenzo) bypasses first-pass via lymphatic absorption — minimal hepatic load.
• TRAVERSE was designed for non-inferiority, not superiority. TRT does not appear to CAUSE MACE in this population at TRT doses. It does NOT mean TRT is risk-free or that supraphysiologic doses are safe.
• Atrial fibrillation increased significantly (3.5% vs 2.4%, HR 1.46). This is a real signal.
• Pulmonary embolism increased (0.9% vs 0.5%) — consistent with the polycythemia mechanism.
• Acute kidney injury increased (2.3% vs 1.5%) — mechanism less clear, possibly hemoconcentration.
• TRAVERSE Bone Substudy (Snyder NEJM 2024, PMID 38231621) found numerically MORE fractures in T arm despite earlier T-Trials BMD gains — surprised the field; possibly increased risk-taking.
• TRAVERSE does NOT extrapolate to supraphysiologic doses in young eugonadal athletes — different population, different physiology, different risk.