Anabolic and lipolytic actions of beta₂-agonists in humans and antidoping challenges

Inhaled beta2‐adrenoceptor agonists (beta2‐agonists) are among the most used substances in competitive sports. The 2020 Prohibited List issued by the World Anti‐Doping Agency restricts use of all selective and non‐selective beta2‐agonists in‐ and out‐ of competition with few exemptions. Formoterol, salbutamol, and salmeterol are allowed by inhalation within defined dosing limits. These restrictions are in place because supratherapeutic use of beta2‐agonist has the potential to be anabolic and to enhance performance, as well as due to potential side effects. Despite substantial documentation that beta2‐agonists exert anabolic and lipolytic actions, these actions are not widely recognized. Furthermore, a common misconception is that the inhaled route does not exert these effects. However, given the high relative systemic bioavailability via the inhaled route, inhalation at high doses can also exert anabolic and lipolytic actions. In this review, we highlight the anabolic and lipolytic actions beta2‐agonists can exert, regardless of the type of beta2‐agonist and the route of administration. The doses needed to provide such effects are also associated with adverse effects and would in most cases be detected in routine doping control. Notwithstanding, the beta2‐agonist regulations are associated with some challenges and given their ability to induce muscle growth and to enhance performance, it is important to continue developing effective detection strategies to prevent potential misuse of beta2‐agonists while allowing treatment of asthmatic subjects without causing adverse side effects or ergogenic actions

An abductive inference approach to assess the performance‑enhancing effects of drugs included on the World Anti‑Doping Agency Prohibited List

Some have questioned the evidence for performance-enhancing efects of several substances included on the World AntiDoping Agency’s Prohibited List due to the divergent or inconclusive fndings in randomized controlled trials (RCTs).However, inductive statistical inference based on RCTs-only may result in biased conclusions because of the scarcity ofstudies, inter-study heterogeneity, too few outcome events, or insufcient power. An abductive inference approach, where thebody of evidence is evaluated beyond considerations of statistical signifcance, may serve as a tool to assess the plausibilityof performance-enhancing efects of substances by also considering observations and facts not solely obtained from RCTs.Herein, we explored the applicability of an abductive inference approach as a tool to assess the performance-enhancingefects of substances included on the Prohibited List. We applied an abductive inference approach to make inferences ondebated issues pertaining to the ergogenic efects of recombinant human erythropoietin (rHuEPO), beta2-agonists and anabolic androgenic steroids (AAS), and extended the approach to more controversial drug classes where RCTs are limited.We report that an abductive inference approach is a useful tool to assess the ergogenic efect of substances included on theProhibited List—particularly for substances where inductive inference is inconclusive. Specifcally, a systematic abductiveinference approach can aid researchers in assessing the efects of doping substances, either by leading to suggestions ofcausal relationships or identifying the need for additional research