As well as the concerns of WADA in defending the spirit of free and fair competition, awareness is also raised when there are known health consequences of drug abuse. The negative health consequences of doping for athletes and the education of support staff are the focus of this narrative review. Clearly, doping and athlete health is a vast area and so two points of delimitation are made up-front. First, we concentrate on cardiovascular (CV) health consequences of drug use. Second, this review focuses on anabolic agents and stimulants. According to WADA's adverse analytical findings report from 2010, anabolic agents accounted for around 60% of adverse findings, with stimulants contributing around 10%. 4 Consequently, the clinical support teams working with athletes must understand the potential CV health consequences when athletes abuse these drugs. Finally, we will discuss the CV effects of cocaine use, as it is one of the most widely used recreational drugs detected in athletes. 4 As well as reflecting on previous data related to the CV health consequences of anabolic steroid, stimulant and cocaine use we have attempted to provide extra context and information in the form of brief case-study exemplars on anabolic steroid and cocaine abuse.

In a bid to improve performance and/or aid recovery, various pharmaceutical products have been used, both openly (legally) and in a clandestine manner against the rules of governing bodies, by a broad array of athletes. 1 The World Anti-Doping Agency (WADA) strictly regulates the use of pharmaceutical products in competitive sport. WADA produced and regularly updates the World Anti-Doping Code that includes a prohibited drug list. This list dictates what is and is not acceptable, from a doping perspective, within sport ( table 1 ). The list has various subsections with some drugs banned both ‘in’ and ‘out’ of competition, while others are banned ‘in’ competition only (eg, ephedrine and the cannabinoids). The WADA list of prohibited substances is further broken down into several subcategories of specific products, including anabolic agents, peptide hormones and growth factors; β-2 agonists; hormone and metabolic modulators; diuretics and masking agents; stimulants; narcotics; cannabinoids; and glucocortocosteroids ( table 1 ). Despite strict rules and punishments being in place in an attempt to limit doping offences, there continues to be those who choose to try and gain an unfair advantage in sport by taking drugs. 3

Anabolic agents

There are a number of drugs that are used in an attempt to increase lean muscle mass. Of these, the most well known is the steroid hormone testosterone (T) and the various analogues that are based around testosterone, usually referred to as androgenic anabolic steroids (AS). In addition to AS there are non-steroid agents that are used in an attempt to generate the same anabolic effects. These include the β-2 agonist, clenbuterol (which is additionally used as an anorectic agent to reduce body fat), human growth hormone (HGH) and insulin/insulin-like growth factors. Other growth factors are commonly used in between courses of anabolic agent use and these include human chorionic gonadotropin (HCG) and erythropoietin (EPO) and more recently selective androgen receptor modulators. Whatever the classification, the purpose of anabolic and growth factors is to stimulate skeletal muscle growth and promote rapid recovery following intensive training. From a clinical perspective it is also worth noting that EPO is predominantly used to boost endurance exercise performance and in general has not crossed over to amateur and recreational sports performers. AS, HGH, HCG and insulin/insulin-like growth factors, however, are routinely used by professional, amateur and recreational athletes.5 Consequently, the likelihood of clinicians coming across users of these particular drugs is much greater.

It is worthy to note that the classification of AS covers a number of structural variants. Classically, AS are classified as water-soluble orally active forms (17-α-alkylated) and lipid-soluble parenteral forms (17-β-esterified). In addition, they are often also classified as either testosterone-based, dihydrotestosterone-based (DHT) or 19-nortestosterone-based (Nandrolone) all of which have differing properties and expected side effects. The situation is further complicated by belief among users, often stemming from anecdotal advice, that some AS are better for predominantly ‘bulking’ (eg. Deca-Durabolin) while others are better suited to losing body fat or ‘cutting’ (eg. Winstrol). Users will often use these different forms of AS in varying quantities. The use of AS is also characterised by periods of use followed by periods of abstinence, or ‘cycles’. This helps to maximise the effects of the drugs while also limiting the negative consequences and allowing the body to normalise following an ‘on’ cycle. Furthermore, users will often supplement their cycles with additional pharmaceutical agents both when bulking (eg, Insulin, human growth hormone) and when losing body fat (clenbuterol, cytomel, 2,4, dinitrophenol). Finally, there are a surprising number of drugs used to attempt to limit side effects of AS use or normalise the hypothalamo-pituitary-gonadal (HPG) axis following an AS cycle. These include estrogen receptor antagonists (tamoxifen), selective estrogen receptor inhibitors (clomifene), aromatase inhibitors (arimidex), 5-α reductase inhibitors (finesteride) and HPG axis stimulators such as HCG.

Evidence of athlete use of AS has been available since the 1950s with AS contributing to c. 60% of adverse findings according to recent WADA reports.6 In the general population there are data showing an increase in the prevalence of AS use.7 Despite such widespread use there is still some controversy as to the CV health consequences of taking AS.8 Large sample epidemiological evidence of the CV health consequences of long-term AS use is lacking, likely because of the reluctance to admit use and/or possession. In addition, evidence for a link between AS use and CV disease outcomes or end-points is mostly limited to case study reports. Published case studies include AS use associated with myocardial infarction,9 stroke,10 embolism11 and other CV health issues (table 2). Although caution should be expressed in implying cause and effect from case studies,8 they can provide direction for case series and experimental studies as well as informing/educating clinical practitioners.

Table 2 Cardiovascular events and risk factors from AS use

Significant research attention has focused on the impact of AS use on CV disease risk factors namely blood pressure, lipid profile, left ventricular (LV) mass, cardiac function and arterial function. Elevated systemic arterial blood pressure is associated with an increased CV disease risk. Compared to healthy controls, AS users have increased resting22 ,26 and exercise22 systolic blood pressure. Conversely, other studies have not observed increased blood pressure in AS user.6 ,24 Differences in the training level of the participants along with age could be responsible for the differences seen in these studies.

AS have also been associated with negative alterations in lipid profiles.27 Changes reported include a decrease in high-density lipoprotein (HDL),28 an elevation in low-density lipoprotein (LDL)24 and reduced apolipoprotein levels,29 possibly through up-regulation of hepatic triglyceride lipase.30 The changes in lipid profiles indicate an increase in atherosclerotic risk. Increases in homocysteine, a naturally occurring amino-acid thought to have a role in vaso-control, and C-reactive proteins (CRP), an acute-phase protein that rises in response to inflammation, have been implicated as risk factors for CV disease. Grace and Davies25 demonstrated a significant increase in CRP in AS users. While Zmuda et al31 observed no significant increases in homocysteine in a group of AS users, Graham et al32 noted a significant elevation in homocysteine in AS users as well as those who had abstained from AS use for 3 months, indicating a possible effect of AS on vitamin B absorption. Previous studies have also suggested a possible link between AS use and thrombotic risk through alterations in haemoglobin levels.33

An increase in LV mass is an independent risk factor for CV disease.34 AS use has been associated with an increase in LV mass,35 ,36 but there is conflicting data.27 ,37 ,38 There are some data in AS users that suggest a reduction in systolic cardiac function38 although this is not a consistent finding between studies.8 A reduction in diastolic function has been observed more frequently and it has been suggested that a reduction in myocardial relaxation/elastance is associated with AS use.27 ,37 ,38 AS use has also been associated with reduced endothelial function in conduit arteries.6 ,24 ,39 Ebenbichler et al40 and Sader et al6 noted a reduced flow-mediated dilation in AS users as well as a reduced vasodilator response to glyceryl-trinitrate.

There is a growing evidence base that AS use can have a negative effect on multiple CV disease risk factors. We present a case study exemplar to illustrate the broad effect of AS use on the CV system.