Testosterone replacement therapy (TRT) for male hypogonadism has been surrounded by cardiovascular controversy since a 2010 trial was halted due to excess cardiovascular events in TRT-treated men. The landmark TRAVERSE trial (2023, NEJM) — a large RCT specifically designed to evaluate cardiovascular safety — has significantly clarified the evidence base, with important implications for clinical practice.
TRAVERSE Trial: Settling the Cardiovascular Question
TRAVERSE (Testosterone Replacement therapy for Assessment of long-term Vascular Events and efficacy ResponSE, n=5,246): men aged 45–80 with hypogonadism (T < 300 ng/dL) plus cardiovascular disease or high cardiovascular risk, randomized to transdermal testosterone vs. placebo for 33 months. Primary outcome: MACE (major adverse cardiovascular events — noncardiac death, myocardial infarction, stroke). Result: testosterone non-inferior to placebo for MACE (7.0% vs. 7.3%). No increase in mortality, MI, or stroke. Important safety signal: TRT significantly increased atrial fibrillation (3.5% vs. 2.4%), acute kidney injury (2.3% vs. 1.5%), and pulmonary embolism (0.9% vs. 0.5%) — these are real risks requiring clinical consideration. Overall conclusion: TRT does not cause heart attacks or strokes in hypogonadal men with cardiovascular disease — addressing the primary concern that had made many clinicians reluctant to prescribe. The specific risks identified (AF, PE, AKI) should inform patient selection and monitoring.
Diagnosis and Clinical Management
Diagnosis: symptomatic hypogonadism requires both (1) morning total testosterone <300 ng/dL on at least 2 morning samples (9–11am) and (2) symptoms (sexual dysfunction, decreased libido, fatigue, loss of muscle mass, depression). Formulations: transdermal gel/cream (most commonly used, avoids injection complications), intramuscular testosterone cypionate/enanthate (effective, lower cost, injection complications), subcutaneous pellets (6-month duration, minor surgical procedure), buccal (twice-daily). Goals: achieve mid-normal range testosterone (450–600 ng/dL). Monitoring: testosterone levels (3 and 6 months, then annually); hematocrit (polycythemia risk — target <52%); PSA (annually, discuss prostate cancer risk — do not prescribe TRT in active prostate cancer); bone density (baseline DXA if osteoporosis risk). For clinical practices monitoring testosterone therapy, our laboratory supplies section and diagnostic equipment catalog support regular metabolic and endocrine monitoring.
