Studies providing supra pharmacologic doses, using maximally trained athletes and testing performance in tasks like weightlifting, are mainly likely to show an effect of AAS. A recent study showing clear, statistically significant increases in muscle mass and strength after AAS administration in a proper placebo-controlled, blinded study may help put these controversies to rest. This complemented previous studies from the same laboratory demonstrating benefit in hypogonadal, HIV-infected men using the same strategy.

Biochemical and anatomical studies show that AAS do significantly influence muscle morphology and biochemistry in humans. Body weight reliably increases after AAS use and part of the increase is in lean body mass, although part also reflects retention of water.

Muscle biopsies in weightlifters reported that both the number of muscle fibers and average fiber size in the trapezius muscle were greater in AAS users than. Controlled studies show that both the number of muscle fibers and the size of individual fibers increase with AAS treatment in animal models. Both of these processes depend upon activation of satellite cells within the muscle. Satellite cells contain androgen receptors. AAS action within these cells to stimulate proliferation may represent an important mechanism of AAS action. The specific genes that are regulated by androgens in the muscle are unknown.

Muscle biopsies in AAS-using power lifters, in comparison to drug free power lifters, showed increased expression of embryonic forms of myosin and the Leu-19 antigen that is expressed in developing myotubes and newly formed myonuclei. This finding supports the hypothesis that AAS trigger both hypertrophy and hyperplasia but does not elucidate the specific genes that are activated. Still, increases in strength can also result not from hypertrophy or hyperplasia but from increased expression of specific elements of the contractile apparatus.

A recent study began by evaluating potassium and caffeine induced contractures. Both the magnitude of potassium-induced contractures and the rate of recovery were greater in slow-twitch muscles of animals that received training and nandrolone. These results suggested changes in both the activation mechanism and recovery mechanisms that sequestrate calcium in the sarcoplasmic reticulum. Enhanced caffeine contractures could reflect enhanced calcium release from the sarcoplasmic reticulum or changes in the calcium sensitivity of the contractile proteins.