I had a chance earlier today to visit with the production crew from Mississippi Public Broadcasting. They’re working on an upcoming television program on body building and were looking for information about the cardiovascular effects of anabolic steroids.
Also today, I came across a new study published this week (online, ahead of print) in the medical journal, JAMA Internal Medicine, that reported on a 40% increase in testosterone replacement therapy in middle-aged men during the time period from 2001-2011. The authors noted that testosterone replacement therapy was often prescribed without an established diagnosis of low testosterone levels (hypogonadism).
So….with steroids on my mind, I thought I’d share some information about these drugs, particularly as they relate to athletes.
What are Anabolic Steroids?
The history of anabolic steroids dates to the mid-1930s when the chemical structure of the male sex hormone testosterone was elucidated. Soon afterward, chemical synthesis of testosterone was possible in the laboratory.
The group of medications that we call anabolic steroids are synthetic derivatives of testosterone. These medications have a variety of arcane names including: nandrolone, methandienone, stanozolol, androsterone, and androstane, among others.
The anabolic steroids have 2 major groups of effects: androgenic effects and anabolic effects. The various available steroids differ from one another in the relative potency of these 2 sets of effects. Each manufacturer’s drug might then be targeted toward a specific use that focuses to a greater extent on one or the other of these sets of effects.
Clinically, the U.S. Food and Drug Administration has approved the use of anabolic steroids for: hypogonadism (eg, low testosterone level); generalized wasting in conditions such as human immunodeficiency virus infection (HIV), acquired immunodeficiency syndrome (AIDS), or cancer; hypoplastic anemias that accompany bone marrow failure or renal failure; growth stimulation in children with growth failure; male contraception; induction of male puberty; and gender identity disorder.
These medications can be delivered orally, intravenously, by intramuscular injection, or by transdermal patch.
The anabolic steroids should not be confused with the corticosteroids that are much more commonly used in clinical practice.
In 1990 the anabolic steroids were added to Schedule 3 of the Controlled Substance Act, making it a federal crime to possess these drugs in the United States without a prescription. For context, other drugs in Schedule 3 include the barbiturates, LSD precursors, ketamine, and some narcotic analgesics. The laws regarding the prescription and possesion of anabolic steroids vary from country to country.
Anabolic Steroids and Sports
The anabolic steroids have been used for decades by athletes of many different sports to gain competitive advantage. Used for this purpose, these drugs are often taken at many times the conventional prescription dosage. At these dosages, the anabolic steroids lead to an increase in muscle mass and likely potentiate the effects of exercise on gaining additional muscle mass and strength.
The first reliable tests for the detection of steroids (or their metabolites) became available in 1974 and anabolic steroids were added to the International Olympic Committee’s (IOC) banned substance list in 1976 and have been on the World Anti-Doping Agency (WADA) banned substance list since its inception in 1999. As such, these drugs are banned by the entire Olympic movement and by all sports organizations that adhere to the WADA code. In addition, these drugs are prohibited by the majority of professional sports organizations in the United States, including the National Football League, National Hockey League, National Basketball Association, and Major League Baseball.
How Many People are Using Anabolic Steroids?
The number of Americans currently using anabolic steroids is unknown, but some estimates have placed that number at more than 3 million. In surveys of steroid usage among body-building or power athletes, rates of up to nearly 70% have been reported, with considerably greater usage among male athletes.
What are the General Side Effects?
Many unwanted side effects have been attributed to anabolic steroids. Some are drug-specific and dose-dependent. The list of adverse effects of anabolic steroids includes: in men, enlargement of the breasts (gynecomastia), suppression of naturally-produced testosterone, decreased sperm production, and testicular atrophy; in women, increases in body hair, decreases in menstrual cycles, and lowering of the voice; development or worsening of acne; and alterations in the mood, with increased aggression. In order to avoid the unwanted side effects of gynecomastia and weight retention, men who use steroids sometimes also take drugs (eg, Arimidex) that limit conversion of the steroids to estrogen.
What are the Adverse Cardiovascular Effects?
Our understanding of the cardiovascular effects of the anabolic steroids comes from a relatively small set of observations made in athletes taking these medications and from a small number of animal studies. Retrospective human studies in this area suffer from important methodologic problems such as: incomplete or inaccurate reporting on drug dosages by athletes; confounding influences of other supplements or medications that athletes may be taking; and the cardiovascular effects of an athlete’s training routine that may mimic some of the effects of steroids.
Some, but certainly not all studies, have shown an increase in blood pressure attributed to anabolic steroids. This issue has been difficult to study in power athletes because of the myriad of factors that influence the blood pressure, including weight-lifting itself. There are certainly anecdotes of finding cases of severe hypertension in athletes who have no other obvious cause than steroids. The amount of blood pressure elevation associated with long-term use of steroids appears to be mild to moderate and the effect may subside if the steroids are stopped.
The majority of studies show that anabolic steroids have an unfavorable effect on the serum lipid profile. These medications can lead to a 20% increase in the unhealthy, “bad” cholesterol (LDL) and also a 20% decrease in the healthy, “good” cholesterol (HDL). The exact mechanism for these changes has not been established. These changes are thought to develop within weeks of starting steroids and can linger for months after these medications are stopped, despite a relatively short pharmacologic half-life measured in days. Some studies have suggested that the oral route of administration may be worse in this regard than the injectable route. These unfavorable changes in the serum lipid profile are noteworthy because there is considerable evidence that high LDL and low HDL levels are associated with increased risk for coronary artery disease, heart attack, and stroke.
Athletes who use anabolic steroids are often found to have thickening of the muscular walls of the left ventricle that we call left ventricular hypertrophy (LVH). The degree of hypertrophy can range from mild to severe. But to date, there has not been a long-term, carefully controlled, prospective study to help sort out the precise effects of steroids. The data regarding which portions of the left ventricle become hypertrophied have been inconsistent, but it appears that the resulting LVH may not be uniform throughout the chamber. It’s important to remember, though, that power exercise alone can produce LVH and that elevated blood pressure alone can produce LVH, and both of these influences will be in play in power athletes.
Sudden cardiac death (SCD) may occur in athletes who are taking anabolic steroids. This appears to be a rare event. In the absence of any other explanation, it might be easy to ascribe such deaths in otherwise healthy athletes to the steroids. But we can only speculate now about the mechanism by which steroid use might predispose the athlete to SCD. Nonetheless, there have certainly been athletes with SCD where autopsy findings have shown severe LVH or cardiac fibrosis (which might predispose to arrhythmias) where no potential cause except the steroids was obvious.
Acute myocardial infarction (MI), or “heart attack” may occur in young athletes who are taking anabolic steroids, often without any prior indication of heart disease. The cause-and-effect relationship between steroids and MI is not completely understood, but we know from animal studies that the steroids may increase platelet aggregation–a step that occurs clinically during sudden blockage of one of the coronary arteries during acute MI. We also know from animal studies that the steroids may increase oxygen demand of the cardiac muscle, potentially leading to a mismatch in blood/oxygen supply and demand during exercise. This may also play a role.
The precise epidemiologic link between steroid use and mortality is yet to be established. Small studies have shown that among users of anabolic steroids, the cause of death, perhaps not surprisingly, is cardiac in up to two thirds. One interesting recent study from Sweden identified users of anabolic steroids by blood tests (toxicology screen) that were administered during evaluations for some other medical problem. The investigators found that, over a several-year period, the mortality rate for users was 2-5 times that for non-users. The study was not controlled, though for many other, potentially important, factors that influence mortality.
To reiterate, our current understanding of the adverse cardiovascular effects of anabolic steroids is based on rather limited information gathered from a small number of research studies. The available reports, though, certainly give a glimpse of unwanted cardiovascular effects that may occur, even if the causal mechanisms are not yet understood. Going forward, we are unlikely to have large-scale prospective studies to gather more information and additional retrospective studies are likely to have the methodologic pitfalls I mentioned above. Given our current understanding, athletes who choose to use anabolic steroids should be aware of the possibilities of high blood pressure, unfavorable lipid profile, structural changes in the heart, and even heart attack or SCD.