Atherogenic effects of anabolic steroids on serum lipid levels. A literature review.Recent surveys and reports suggest that many athletes and bodybuilders abuse anabolic-androgenic steroids AAS. However, scientific effect of anabolic steroids on lipids on the cardiac and metabolic complications of AAS abuse are divergent and often conflicting. A total of 49 studies describing 1, athletes were reviewed to investigate the cardiovascular effects of the abuse of AAS. Although studies were typically small and retrospective, some associated AAS abuse with unfavorable effects. Otherwise healthy young athletes abusing AAS may show elevated levels of low-density lipoprotein and low levels of effecg lipoprotein.
Recent surveys and reports suggest that many athletes and bodybuilders abuse anabolic-androgenic steroids AAS. However, scientific data on the cardiac and metabolic complications of AAS abuse are divergent and often conflicting. A total of 49 studies describing 1, athletes were reviewed to investigate the cardiovascular effects of the abuse of AAS. Although studies were typically small and retrospective, some associated AAS abuse with unfavorable effects. Otherwise healthy young athletes abusing AAS may show elevated levels of low-density lipoprotein and low levels of high-density lipoprotein.
Although data are conflicting, AAS have also been linked with elevated systolic and diastolic blood pressure and with left ventricular hypertrophy that may persist after AAS cessation. Finally, in small case studies, AAS abuse has been linked with acute myocardial infarction and fatal ventricular arrhythmias. In conclusion, recognition of these adverse effects may improve the education of athletes and increase vigilance when evaluating young athletes with cardiovascular abnormalities.
Anabolic-androgenic steroids AAS are synthetic derivatives of testosterone that were originally developed in the late s. Many effects of AAS abuse are unclear. Although side effects are rare at therapeutic doses, abusers typically use 5 to 15 times the recommended clinical doses of AAS.
Moreover, athletes often abuse AAS for years, prolonging the potential for harm. Review of published reports was limited to the period from January 1, , to December 31, , because widespread testing became available in the United States and Europe at the end of In aggregate, studies evaluated lipoprotein concentrations in subjects, blood pressure in , left ventricular LV dimensions in , and sudden death in We also report 4 key animal studies whose results shed insights into potential mechanisms linking AAS abuse with cardiovascular disease.
AAS include many agents with chemical structures derived from cholesterol that are synthesized in the liver and then metabolized in the adrenal glands and testes to AAS. Their structure resembles that of corticosteroids, explaining some similarities in actions in terms of renal sodium retention and hypertension. AAS are abused by athletes primarily to increase lean muscle mass, enhance appearance, and improve performance. Mortality appears to be significantly higher in AAS abusers than in nonabusing athletes.
In a retrospective case-cohort study of AAS users and 1, controls average age 23 years , 12 AAS users died during the study period, 22 providing a standard mortality ratio of Of the 1, athletes who did not abuse AAS, 22 died during the study period, resulting in a standard mortality ratio of 6. Many mechanisms have been proposed to explain potential adverse cardiovascular events of AAS. The physiologic and pharmacologic mechanisms of action of AAS on vascular structure and function are incompletely understood.
AAS bind to androgen receptors in the heart and major arteries, 26 and physiologic levels e. AAS abuse has been linked with abnormal plasma lipoproteins Table 1. Although some studies have shown an association between AAS and elevated LDL, no definitive mechanism has been established. Baldo-Enzi et al 39 suggested that serum LDL levels may increase through the induction of the enzyme hepatic triglyceride lipase and catabolism of very low density lipoprotein.
Hepatic triglyceride lipase induction may also catabolize HDL and reduce its serum levels. The control group included bodybuilders who denied AAS abuse. Other studies have confirmed these effects Table 1. The relation between AAS abuse and blood pressure is controversial. A link between AAS abuse and elevated blood pressure has been observed in some studies, 14 , 43 , 59 , 60 whereas others have shown no association.
Other studies support these data Table 2. In some studies, AAS remain detectable after self-reported discontinuation. Importantly, the link between AAS abuse and elevated blood pressure is not seen in all studies. Measurements were made when users were taking AAS and during the withdrawal stage of cycling. Misclassification of athletes was minimized by measuring gonadratropin levels, follicle-stimulating hormone, and luteinizing hormone, which decreased significantly in users.
Moreover, Lenders et al 14 did not show elevated blood pressure in AAS users compared with nonusers in a larger population. Another confounding variable that some investigators neglect to report relates to cuff size. In athletes with larger arms, regular sized blood pressure cuffs could overestimate blood pressure.
Analysis is complicated further by variability in exercise regimens, variability in dosing and duration of AAS use, and potential biases in unblended studies. Clearly, additional studies are necessary to definitively reveal a link between AAS and blood pressure.
Possible associations between AAS and LVH may be explained as secondary to hypertension or as a direct effect on the myocardium. Notably, studies in isolated human myocytes have shown that AAS bind to androgen receptors and may directly cause hypertrophy, 73 — 75 potentially via tissue up-regulation of the renin-angiotensin system.
In a retrospective case-control study, Krieg et al 65 performed nonblinded echocardiographic measurements on 14 AAS users, 11 age-matched nonuser strength athletes, and 15 age-matched sedentary controls. In contrast, Dickerman et al 15 and others 77 have reported that AAS abuse is associated with increased LV posterior wall and interventricular septal thickness compared to non-abusing athletes Table 3.
A variety of agents and doses were noted in the abusers. However, these studies are somewhat difficult to interpret, because most studies did not account for differences in exercise protocols, and most were not blinded.
As always, however, an important caveat is the lack of control for occult AAS abuse. Chung et al 82 conducted a randomized, double-blind, placebo-controlled study in which 30 healthy men were separated into 3 groups receiving weekly testosterone mg, nandrolone decanoate mg, or matching placebo injections for 4 weeks. After 4 weeks, blinded echocardiography showed that only the testosterone group had a significant increase in LV end-systolic diameter, although this remained within the normal range.
Studies observing LVH related to AAS abuse reported that it likely reverses after discontinuing the agent, although with persistent effects for a prolonged period. Alarming data have linked AAS with fatal events, although these are mostly case-control studies and case reports of acute coronary syndromes, MIs, and ventricular arrhythmias.
In the absence of carefully conducted animal experiments, it is felt that AAS abuse may cause cardiac ischemia by exaggerating oxygen demand at peak exercise, potentially precipitated by accelerated atherosclerosis from lipoprotein abnormalities over years of abuse. The relative clinical contributions of these mechanisms are unclear. Nevertheless, their combination may plausibly explain MIs or ventricular arrhythmias in young athletes with no cardiac risk factors, 83 , 91 in many of whom AAS abuse has been ruled the primary cause of death.
Similar cases have been reported by others. Acute angiography revealed extensive left anterior descending coronary artery thrombosis, which was managed by thrombolysis. Angiography in the subacute phase confirmed very mild luminal irregularity at the site of previous thrombosis.
Electrocardiogram of a year-old male athlete presenting with acute MI, showing anterior precordial Q waves and ST-segment elevation. The patient, who admitted to recent nandrolone abuse, had been previously healthy and without cardiac risk factors. Angiography revealed thrombosis in the left anterior descending coronary artery but no significant atherosclerotic narrowing. Reproduced from Recent Prog Horm Res. Finally, there are numerous anecdotes of potentially lethal ventricular arrhythmias in AAS-abusers.
The most commonly observed arrhythmias, typically occurring during physical exertion, include atrial fibrillation, ventricular fibrillation, ventricular tachycardia, and supraventricular and ventricular ectopic beats. Postmortem examination revealed ventricular hypertrophy, myocardial fibrosis, and acute MI, and the cause of death was attributed to arrhythmic sudden death secondary to AAS abuse.
More organized case series are needed to define to what extent such cases represent occult forms of hypertrophic cardiomyopathy or other arrhythmogenic conditions. This review included 1, subjects, but the major variables discussed included only a fraction of these subjects. Many studies that were reviewed were observational, cross-sectional studies with small sample sizes and single case reports that may explain variability in the reported data. Although prospective, randomized controlled studies would be ideal, such studies are also difficult to conduct because they must control for occult AAS use and recruit large samples of competitive athletes willing to disclose their illegal use of AAS.
Many studies were not blinded, particularly with regard to blood pressure and echocardiographic assessment.
Others did not account for variability in AAS dosage and cumulative duration of use or compared dissimilar exercise regimens e. Many studies also did not specify the reasons for the discontinuation of AAS and whether such athletes continued exercising to the same degree. In addition, most studies followed AAS abusers for short periods, and many were too small to perform multivariate corrections for other risk factors.
Some studies on the adverse cardiometabolic effects of AAS may also reflect publication bias. Finally, AAS are often coabused with growth hormone, erythropoietin, and agents including creatine, ephedra alkaloids, and herbal supplements, although most AAS reports neither documented nor controlled for these agents. This is important because growth hormone may lead to cardiomyopathy, abnormal lipoprotein profiles, 97 , 98 and LVH.
Nevertheless, AAS alter lipids, may affect LV dimensions, and have an unclear role in blood pressure elevation in athletes.
Physicians should consider the possibility of AAS abuse when treating young athletes with abnormal lipids, LV dimensions, and potentially even blood pressure elevation.
National Center for Biotechnology Information , U. Author manuscript; available in PMC Jul Narayan , MB, MD. The publisher's final edited version of this article is available at Am J Cardiol. See other articles in PMC that cite the published article. Abstract Recent surveys and reports suggest that many athletes and bodybuilders abuse anabolic-androgenic steroids AAS.
Clinical pharmacology of AAS AAS include many agents with chemical structures derived from cholesterol that are synthesized in the liver and then metabolized in the adrenal glands and testes to AAS. The public health problem: Mortality in AAS abuse: Potential mechanisms The physiologic and pharmacologic mechanisms of action of AAS on vascular structure and function are incompletely understood. Open in a separate window. AAS, acute MI, and sudden death Alarming data have linked AAS with fatal events, although these are mostly case-control studies and case reports of acute coronary syndromes, MIs, and ventricular arrhythmias.
Discussion Limitations This review included 1, subjects, but the major variables discussed included only a fraction of these subjects. Hoberman J, Yesalis CE. The history of synthetic testosterone. Appetite stimulants and anabolic steroid therapy for AIDS wasting. J Clin Endocr Metab. Sports Illustrated, the mainstream press and the enactment of drug policy in major league baseball.
Behavioral and physiological responses to anabolic-androgenic steroids. Parkinson A, Evans NA.