Downregulation of Androgen Receptors upon Anabolic-Androgenic Steroids: A Cause or a Flawed Hypothesis of the Muscle-Building Plateau?

Abstract

Researchers and health practitioners seek to understand the upper limit of muscle hypertrophy under different conditions. Although there are models to estimate the muscle-building threshold in drug-free resistance training practitioners, little is known about the population using anabolic–androgenic steroids (AASs) in this regard. Because of a plateau effect of muscle hypertrophy upon AAS regimens, there is a hypothesis among clinicians and enthusiasts that AASs downregulate skeletal muscle androgen receptors (ARs). Conversely, in this narrative review, we show that seminal and recent evidence—primarily using testosterone and oxandrolone administration as human experimental models—support that AASs upregulate ARs, eliciting greater anabolic effects on skeletal muscle receptors through a dose-dependent relationship. Thus, to date, there is no scientific basis for claiming that myocyte AR downregulation is the cause of the AAS-induced plateau in muscle gains. This phenomenon is likely driven by the neutral nitrogen balance, but further research is imperative to clarify the intrinsic mechanisms related to this landscape.