When some people lift weights, their bodies make more of a certain enzyme—but only if they’re the type who gains muscle easily. People who don’t gain much muscle don’t see this enzyme change. And even when the enzyme goes up, it doesn’t match up with how much muscle they gain, so it probably doesn’t cause the muscle growth—it just happens along with it.

A longitudinal study in humans where participants undergo a standardized resistance training program for 12–16 weeks, pre- and post-intervention muscle biopsies are taken to measure 5α-reductase expression, and muscle hypertrophy is quantified via DEXA or MRI. Participants are prospectively classified as high or low responders based on pre-specified hypertrophy thresholds (e.g., >10% vs. <5% increase in muscle cross-sectional area). The analysis tests whether 5α-reductase upregulation occurs only in high responders and whether the magnitude of enzyme change correlates with hypertrophy magnitude.

A within-subject crossover trial where participants receive a 5α-reductase inhibitor (e.g., finasteride) or placebo in randomized order during two separate 8-week resistance training blocks. Muscle hypertrophy and 5α-reductase expression are measured in muscle biopsies after each block. If inhibiting the enzyme blocks hypertrophy only in high responders, it supports a causal role; if hypertrophy proceeds unchanged, it supports the claim that enzyme upregulation is a consequence.

Human primary myoblasts are differentiated into myotubes and subjected to mechanical stretch (simulating resistance training) with or without pharmacological inhibition or overexpression of 5α-reductase. If stretch increases enzyme expression only in myotubes derived from high-responder donors (pre-screened for hypertrophy potential), and enzyme manipulation does not alter myotube size, it supports the claim that enzyme upregulation is a consequence, not a driver.

A large observational cohort study (n>200) measuring baseline and post-training 5α-reductase expression and muscle hypertrophy. Statistical models test whether the change in enzyme expression predicts hypertrophy after controlling for baseline factors, and whether the relationship differs between pre-defined high and low responders.

In-depth molecular profiling of muscle tissue from individuals at the extreme ends of the hypertrophy response spectrum (top 1% and bottom 1%) after identical training. If 5α-reductase is consistently upregulated only in high responders and no other pathway differences explain the hypertrophy difference, it supports the claim that enzyme change is a downstream marker.