Physiological basis behind ergogenic effects of anabolic androgens

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Highlights

  • Anabolic androgenic steroids (AAS) are widely abused, despite adverse effects.

  • AAS increase muscle strength independent of endogenous testosterone levels or age.

  • AAS have effects on the vasculature, erythropoiesis and the central nervous system.

  • AAS act by classical androgen receptor mediated and by rapid non-genomic effects.

Abstract

Anabolic androgenic steroids (AAS) are widely abused by the sporting community. Demonstrating performance enhancing effects of AAS in rigorous scientific studies is fraught with difficulty. In controlled studies, AAS have consistently been reported to increase muscle mass and strength. The clinical evidence that these anabolic effects are independent of, and additive to exercise are supported by preclinical studies suggesting that AAS and exercise affect muscle by overlapping, yet distinct mechanisms. AAS may also improve performance by their actions on other organ systems, such as the vasculature, and the erythropoietic and central nervous system, although this evidence is less strong. While most of the actions of AAS are thought to be mediated via classical androgen receptor-mediated genomic signalling, AAS may also produce rapid effects via non-genomic mechanisms.

Introduction

Despite their well-publicized adverse health effects (Basaria, 2010), anabolic androgenic steroids (AAS) are among the most commonly abused performance enhancing drugs among athletes. This reflects the assumption widely held by the sporting community and most of the general public that AAS improve physical performance. Certainly, authorities in the former German Democratic Republic believed this too, evidenced by a large-scale state-sponsored doping program in the 1980ies, and the involved scientists even used the data generated to obtain research higher degrees (Dickman, 1991). This period temporarily coincided with peak numbers of Olympic medals won by East German athletes.

However, the scientific evidence supporting the ergogenic (performance enhancing) effects of AAS remains scant. This is largely because it is all but impossible to definitively prove performance-enhancing effects by AAS by adequately designed randomised clinical trials (RCT) that replicate what athletes actually do in real life. It is unethical to conduct RCTs on illicit substances, or to randomise participants to vastly supraphysiological doses of androgens even if these are approved for clinical use. Available RCTs have generally not exceeded 600 mg of testosterone a week (approximately 5 times the conventional replacement dose) and have been short-term, while athletes may self-administer androgens up to 100- to even 1000-fold in excess of replacement doses, producing circulating testosterone levels two to three orders of magnitude above the healthy male reference range, and often for prolonged periods. The maximal anabolic dose of testosterone is not known, but almost certainly vastly exceeds 600 mg of testosterone a week, given that anabolic actions have been predicted to achieve a plateau only at doses approximately 2 log units higher that the minimal effective dose of testosterone (Storer et al., 2003). In addition, it is not feasible to conduct RCTs in elite athletes themselves that reliably control for important variables such as nutrition, exercise and covert use of performance enhancing drugs other than AAS.

The best currently available evidence clearly supports anabolic effects of androgens on skeletal muscle mass and strength in hypogonadal or eugonadal men irrespective of age. However, the extent to which this anabolic effect improves physical performance has been more difficult to assess. More limited evidence suggest that actions on the central nervous system, erythropoiesis and the vasculature may also contribute to the ergogenic effects of AAS (Fig. 1). In this brief review, we will focus our discussion on the evidence from key clinical studies in men. We will also highlight important findings from preclinical mechanistic studies.

The material presented is based on peer-reviewed journals indexed on the PubMed database from 1970 to November 2016, using, in multiple combinations, the following search terms “anabolic androgenic steroids, oxandrolone, stanozolol, nandrolone, trenbolone, physical performance, performance enhancing drugs, athlete, and testosterone”, limited to English and studies in males. In addition, pertinent review articles were searched for additional publications, and relevant articles were selected.

Section snippets

Clinical studies

Following decades of controversy regarding anabolic effects of AAS, a 1996 landmark study by Bhasin et al. (1996). overcame many of the limitations of previous clinical trials. This carefully conducted RCT randomised healthy young eugonodal men to supraphysiologic testosterone enanthate (600 mg per week, about 6-times the replacement dose) or placebo for 10 weeks and standardized potentially confounding variables such as the amount of exercise and nutritional intake. While both testosterone

Possible performance enhancing effects of AAS other than muscle anabolism

While the evidence for anabolic effects of AAS on muscle hypertrophy and strength based performance measures, as far as assessable within the ethical and logistic framework of scientific studies, is consistent, whether AAS improve other aspects of athletic performance is much less clear. For example, increased body mass (lean or otherwise) may be detrimental for marathon runners or triathletes. Yet, AAS are widely abused by the sporting community, even for disciplines where increased strength

Summary

Replicating real life AAS abuse patterns which involve vastly supraphysiologic multidrug regimens and other high risk behaviours in scientific studies is neither possible nor ethical. Therefore the scientific evidence validating the perceptions of the sporting community is relatively limited and are largely derived from clinical studies in non-athlete populations using modestly supraphysiologic androgen dosing, and from animal experiments. There are multiple potential mechanisms by which AAS

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Acknowledgements

The authors have nothing to declare.

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