Results from this study are consistent with previous findings showing LV diastolic dysfunction10–12
and subclinical LV systolic impairment10
in AAS users. However, our results suggest that the cardiac impairment in long-term AAS users may be more severe than previously reported. Specifically long-term AAS users were found to have significant LV systolic dysfunction – both by relative standards (in comparison to the AAS non-users cohort) and absolute standards (as defined by current clinical practice). To our knowledge, this is the first study demonstrating an association between long-term AAS use and a clinically relevant reduction in LV ejection fraction.
There is a well-established relationship between LV dysfunction and exposure both to certain medications29
and to some drugs of abuse.30–30
Further, the prognostic importance of toxin-induced cardiac dysfunction has been well documented.33–36
Data from this study suggest that AAS, particularly when used over long durations, may be another important cause of toxin-mediated myocardial impairment. Although confirmatory data are required, results from this study suggest that AAS exposure should be a diagnostic consideration among individuals with asymptomatic LV dysfunction or incident heart failure.
Although several previous studies have reported mild cardiac dysfunction, LV dysfunction among our AAS users was more severe than previously reported. Several hypotheses might explain this discrepancy. First, our AAS users were several years older, on average, than those in two of the three most recent previous studies.10,12
Second, these previous studies selected “top-level competitive bodybuilders,”10
or individuals from “bodybuilding studios,”12
– thus possibly favoring healthier individuals with better cardiac function than the largely non-competitive individuals21
in our study. Finally, the specific AAS compounds and dosages typically used by our American participants may have differed from those of participants in previous studies, which were largely conducted in Europe.
It is noteworthy that our analysis revealed no significant relationship between cumulative AAS use and cardiac dysfunction. This observation suggests that AAS-associated cardiotoxicity might perhaps be only partially and unpredictably related to lifetime dose, in a manner similar to the cardiac toxicity of alcohol.37
Further work is required to determine whether cardiac function is influenced by factors such as the recency of AAS use (e.g., current vs. long past), specific AAS used (e.g., possibly more toxic oral agents5,38
versus injectable agents), duration of exposure to very high doses (e.g., ≥ 2000 mg per week), or concomitant use of other drugs (e.g., human growth hormone39,40
There are several important limitations to this study. First, our sample might not be representative of the overall source population of long-term AAS users or comparison weightlifters. Although we used recruitment procedures designed to generate a sample that is maximally representative,20,21
it is possible that the group of AAS users in the present study is not entirely representative of the overall population. Second, our sample sizes were small and unequal. However, this limitation would likely produce false-negative
findings (i.e., type II errors) rather than false-positive results due to the reduced statistical power afforded by small sample sizes. Therefore, the highly statistically significant findings in the present study, despite small sample sizes, suggest that the association between AAS use and cardiac pathology may be particularly strong (i.e., a very large effect size). Conversely, the possibility of a type II error must be considered in instances where group comparisons were not significant. For example, the lack of association between AAS exposure and cardiac dysfunction must be interpreted with caution. Future study with adequate statistical power is warranted to examine this issue. A third limitation is our reliance on participants’ self-reporting of AAS use. We recognize that errors based on self-report could have arisen if: 1.) actual AAS users denied use and were misclassified as non-users; 2.) individuals classified as non-users had unknowingly ingested supplements contaminated with actual AAS; or 3.) individuals classified as users had ingested only counterfeit black-market AAS and hence not used genuine drugs. However, each of these forms of misclassification would only narrow the differences between groups, causing us to underestimate the true association of AAS use with cardiac pathology. A fourth limitation is our use of retrospective exercise exposure assessment and the possibility that AAS-users differed from non-users with respect to exercise intensity. However, it is unlikely that this factor contributed to our observations as no prior studies have demonstrated LV dysfunction secondary to intense, sustained exercise training. Finally, the cross-sectional nature of this exploratory study does not permit definitive conclusions about the long-term clinical implications of our findings. This represents an important area of future work.
In summary, data from the present study suggest that AAS-induced LV dysfunction may be greater than previously reported. The reductions in LV systolic function observed in this group of AAS users are of a magnitude shown to increase the risk of heart failure and sudden cardiac death in other populations.41,42
Further work is needed to confirm our findings and to determine the extent to which AAS-associated cardiac dysfunction leads to adverse clinical outcomes.