Testosterone (supraphysiologic use)

The verdict

Our read at a glance.

Whether the safety record of replacement-dose testosterone tells you anything about the doses used to build muscle.

The signal

Two things are established and they are not the same thing. First, supraphysiologic testosterone builds muscle: the classic placebo-controlled work showed that a dose well above replacement increased fat-free mass and strength, and did so even without training, which settled the efficacy question decades ago. Second, testosterone replacement in men with diagnosed hypogonadism has an approved indication and a large modern trial programme examining cardiovascular safety at replacement doses. The gap between those two bodies of evidence is where this memo lives. The trials that reassure people about safety were run at replacement doses in hypogonadal men. The trial that proves the muscle effect used a dose several times higher in healthy men, for ten weeks.

The unknown

Long-term cardiovascular, haematological and endocrine outcomes at the doses actually used, which have never been studied prospectively and will not be, because no ethics committee will approve the trial. Everything claimed about long-run safety at those doses is extrapolation from a different population taking a different amount.

Our read

The compound where the honest answer is uncomfortable in both directions. It unambiguously works, which is why hedging about efficacy is not credible. And the safety data people cite to justify it were generated at a fraction of the dose in a different population, which is why confidence about long-term safety is not credible either. Approved for hypogonadism is not evidence for a cycle.