Testosterone / TRT

Overview

Testosterone replacement therapy (TRT) is one of the most well-characterized hormone therapies in medicine, with decades of clinical use for hypogonadism. FDA-approved formulations span injectable, transdermal, and oral routes. The TRAVERSE cardiovascular safety trial (2023) provided long-awaited safety data.

Mechanism of Action

Testosterone binds the androgen receptor (AR), translocating to the nucleus to modulate gene expression across muscle, bone, fat, brain, and reproductive tissues. AR-mediated transcription upregulates genes involved in protein synthesis (myofibrillar proteins), suppresses myostatin, and modulates IGF-1 signaling.

Evidence Base

FDA-approved for male hypogonadism with extensive RCT data including the TRAVERSE trial (n=5,246). Endocrine Society clinical practice guidelines provide evidence-based dosing and monitoring recommendations. Published literature spans thousands of studies over 80+ years.

Safety Considerations

FDA-approved with well-defined safety profile. Monitoring requirements include hematocrit (polycythemia risk), PSA, lipids, and liver function. In TRAVERSE, testosterone was noninferior to placebo for major adverse cardiac events, though atrial fibrillation, acute kidney injury and pulmonary embolism were more frequent with testosterone. Labeled contraindications include breast cancer in men and known or suspected prostate cancer; Endocrine Society guidelines also recommend against starting therapy with elevated hematocrit or untreated severe obstructive sleep apnea.

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