Meta-regression analyses provided in R software were conducted to explore the association between studies’ publication year and outcome measures . Data extraction was performed independently by two reviewers (RM and LF), with disagreement resolved by discussion. • Levels of AI detected are not between the acceptable range defined for original productsa (quantitative) • Levels of active pharmaceutical ingredients (AI) detected are between the defined range of the declared formulation defined by the individual studya (quantitative) Injectable testosterone, synthetic AAS, other hormones and adjunctive therapies can easily be purchased over the internet and are delivered to a consumer’s home without prescription 4, 6, 8. Due to lack of reporting, precise prevalence and demographic information on the use of these substances is challenging . Historically, the majority of AAS users were professional or competitive athletes, but nowadays survey data has revealed that over 75% of AAS users are non-competitive bodybuilders or athletes, who are mostly motivated by cosmetic benefits over performance enhancement from AAS use 4, 6, 8–13. AAS belong to the broader group of image and performance enhancing drugs (IPEDs) and are widely used as a convenient and easy method to improve body image and sport performance goals . As discussed earlier in this book, the anabolic steroid market has seen a significant shift from predominantly regulated pharmaceutical and veterinary sources to a sprawling underground laboratory network. All data generated or analyzed during this study is included in this published article and its supplementary information files. To our knowledge, there is currently no published evidence on the controlled use of prescription testosterone through health care channels or drug testing services for AAS and other IPEDs yet. Although striving for abstinence of those substances is the preferred way, this strategy has proven to be inefficient over the past decades, even more leading to a massive unregulated black market for doping agents. Besides the problems with chemical quality, our systematic review provides further evidence of microbiological contamination of those substances. We want to highlight one particular adverse event of those substances that can become a motivator for continued use and an increased risk of continuously being exposed to counterfeit or substandard substances, the "AAS dependence syndrome" . These substances can easily be acquired over the internet, leading to a substantial black market. We strongly oppose the use of anabolic steroids or any illegal or banned substances. We strongly oppose the use of anabolic steroids or any illegal or bannedsubstances. The potential for untested and contaminated products compoundes the health risks. Manufacturing and Quality Control Challenges Unlike their legitimate counterparts, underground labs do not maintain high standards in manufacturing processes. These labs rarely, if ever, test their raw materials or final products. AC provided methodological expertise on biochemical analysis of the samples. This may have resulted in some bias of the studies included and a bias in our statistical summary and conclusions. One strategy could entail the controlled use and availability of these substances through proper health channels. Different harm reduction strategies could be employed to limit this user community from either getting in contact with fake AAS from the black market or to promote safer use and informed decision making. There is a large and increasing number of individuals who are possibly exposed to these fake AAS on the black market. Graham and colleagues demonstrated contamination with bacterial skin commensals during microbiological analysis of their samples. We demonstrate that on some occasions completely different pharmaceuticals were identified during the analysis, such as quinine (antimalarial drug), instead of AAS. In Europe, AAS from the black market appear to be more likely to be substituted and less likely to be inert, but also less likely to be over-concentrated compared to Brazil. Interestingly, this systematic review showed significant differences between the two included world regions. But in addition, products that contain the labeled substances can still be over-concentrated or under-concentrated. Among the included studies, most approaches are based on liquid chromatography coupled to mass spectrometry (LC–MS/MS) 32, 42, 47, 49, 50, or gas chromatography coupled to mass spectrometry (GC–MS) 32, 35, 40, 42, 47, 49, 51–54. There is some evidence within the analyzed literature that the amount of seized or confiscated compounds increased over the observation period 26, 34, with one documented significant, i.e. 5.2-fold increase of seized anabolic steroids (1,468/282) over a 5 year period . We provide evidence that AAS are more likely to be under-concentrated than over-concentrated if they are of substandard quality. In the case of mislabeled AAS acquired on the black market, it is currently not exactly known what is consumed by the user. In this systematic review we demonstrate that the real composition, the type of production, concentration, quantity, quality, and purity are often not declared on the label, and labels are even misleading. Different anabolic steroids come with compound or class-specific and unspecific adverse events. We further show a limited geographical scope of included studies, with all studies being from countries in Europe or Brazil. Underground laboratories emerged both locally and in countries with lax legal regulations and it is described that an 'anabolic steroid tourism' and large networks of online resellers emerged, simplifying the illegal acquisition of anabolic steroids .
