doping

Triathletes and Doping

January 29, 2014 By Larry Creswell, MD Leave a Comment

At my column this month at Endurance Corner, I wrote about age group triathletes and doping. Based on athlete questionnaires, a recent study found that about 15% of age group triathletes at three long course events in 2013 reported some form of doping in the preceeding year. I shared some information about the study and its findings as well as some of the cardiovascular concerns with the common doping agents.

Looking at the Tweets and comments today, some are surprised the rate is so high….and others are surprised it’s so low. I’m not surprised.

Adderall, Athletes, and the Heart

November 2, 2013 By Larry Creswell, MD 2 Comments

Last week I got an inquiry from a reader about the prescription drug Adderall, asking in particular about the heart risks for athletes who might be taking the drug.

Although we’ll be talking about Adderall in particular, much of the information here will apply to other stimulants as well.

My quick take….

Like any drug, there’s both good and bad with Adderall. For athletes who legitimately need the drug, though, the heart risks appear to be small provided that the athlete doesn’t have any serious underlying heart problems. The drug can probably be used safely if both athlete and physician are aware of the potential risks.

What is Adderall?

Adderall is the brand name for a central nervous system stimulant composed of a 3:1 mixture of the salts of d-amphetamine and l-amphetamine. The U.S. Food and Drug Administration (FDA) has approved its use for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy.

The drug is available in immediate release and extended release forms (Adderall XR) in dosages of 5-30 mg. Generic formulations are also available.

The U.S. Drug Enforcement Agency (DEA) has placed Adderall on its Schedule 2 list of drugs–those with a high potential for abuse, with the potential for leading to severe psychological or physical dependence. There are both federal and state regulations that apply to prescriptions for Schedule 2 drugs. In my home state of Mississippi, a handwritten prescription is required, refills are not permitted, and the prescription must be filled by a pharmacy within 90 days. There are stiff penalties for trafficking in Schedule 2 drugs.

In the United States, the prevalence of ADHD in children age 4-17 is nearly 10% and the prevalence in adults is nearly 5%. About two thirds of affected children are treated with prescription drugs.

Adderall and the Athlete

For athletes, there seem to be 3 relevant questions:

What are the rules governing the use of Adderall by athletes?
Does Adderall provide a competitive advantage?
What are the risks?

The Rules

For NCAA athletes, all stimulants are banned. There is a policy which allows for medical exceptions for banned substances that are used for legitimate medical purposes. In the case of Adderall, pre-approval from the NCAA is not needed for use, but the athlete must maintain documentation from his/her physician in the on-campus medical record that includes the diagnosis, course of treatment, and current prescription. If such an athlete is tested positive for the stimulant, the documentation is then used, after the fact, to obtain an exception from penalty.

All stimulants are included in the World Anti-Doping Agency’s list of substances that are banned in-competition. The WADA banned substance list has been adopted by all sports federations of the Olympic movement and many others as well. A complete list of signatories can be found at the WADA website. Athletes with a legitimate medical need for a banned substance can apply for a therapeutic use exemption (TUE). Information about the process for obtaining a TUE is posted at the WADA website. WADA recommends reassessment for the need for continued treatment every 3-4 months.

Adderall and other stimulants are banned by the National Football League (NFL), Major League Baseball, National Basketball Association (NBA), Major League Soccer, but athletes can obtain a therapeutic use exemption. Interestingly, nearly 10% of Major League Baseball players have obtained such an exemption. The drug is banned completely in the National Hockey League (NHL).

Competitive Advantage?

When used to treat ADHD, particularly as part of an comprehensive treatment plan that includes psychological, educational, and social measures, Adderall can be effective in reducing the inattentive or hyperactive-impulsive symptoms that are characteristic of the disorder.

In individuals without ADHD, the effects of Adderall are not characterized as completely. Nonetheless, there is reportedly increasing use of Adderall in this situation, particularly among college students and various athlete groups. In the college setting, students take stimulants like Adderall to increase their attentiveness and reduce their fatigue, especially in situations such as studying for exams or completing end-of-term projects.

There is also ample reason to believe that stimulants such as Adderall might provide a competitive advantage for athletes. From my vantage point, this issue doesn’t seem to be very well studied (in large part because of the bans), but there is at least some evidence to show that these drugs can produce increases in both strength and endurance, better concentration, and improve reaction time, especially when fatigued.

The Risks

For Adderall, like any prescription drug, information about the known risks can be found in the drug’s package insert.

Let me quote the entire black box warning:

Amphetamines have a high potential for abuse. Administration of amphetamines for prolonged periods of time may lead to drug dependence and must be avoided. Particular attention should be paid to the possibility of subjects obtaining amphetamines for non-therapeutic use or distribution to others, and the drugs should be prescribed or dispensed sparingly. Misuse of amphetamine may cause sudden death and serious cardiovascular adverse events.

A variety of side effects are mentioned in the package insert, including emergence of new psychotic or manic symptoms, aggression, long-term suppression of growth, seizures, and visual disturbances. Mention is also made that the effects of long-term usage are not well studied and that the usefulness of the drug for any particular patient should be carefully assessed periodically.

The package insert goes on to discuss cardiovascular warnings.

In children and adolescents, sudden death has been reported in patients treated with Adderall who also have heart problems like structural heart abnormalities, cardiomyopathy, or heart rhythm abnormalities. Patients with any of these heart problems are advised NOT to take Adderall.

In adults, sudden death, stroke, and heart attack have all been reported in patients taking Adderall at typical prescription dosages. It is recommended that patients with structural heart abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or coronary artery disease should NOT take Adderall.

For any patient with high blood pressure, special precaution is advised when prescribing Adderall. Because Adderall is known to increase both the heart rate and blood pressure, special caution and careful follow-up is recommended.

Recommendations are offered for the cardiac evaluation of patients who are being considered for treatment with Adderall. Attention should be devoted to a careful medical history, family history (with particular attention to sudden death, ventricular arrhythmias), and physical exam that focuses on heart and vascular health. Additional investigation with EKG and echocardiogram may be indicated depending on the findings. Finally, patients treated with Adderall who develop any serious warning signs of heart disease (eg, exertional chest pain/discomfort, syncope or blacking out) should be re-evaluated.

Summary

In summary, Adderall is a stimulant that is effective for the treatment of patients with ADHD. Although prescription use of the drug is tightly controlled, there is ample prescription mis-use of the drug among individuals without ADHD or other medical reason for its use. For athletes, the drug is performance-enhancing and is banned by many sports organizations. Whatever its use, Adderall carries a small but real risk of serious cardiovascular side effects, especially among users with underlying heart conditions, whether known or unknown. Athletes and their doctors should be aware of these risks and consider cardiovascular screening and careful cardiovascular follow-up when this drug is used.

Related Posts:
1. Heart Medications, WADA, and the Athlete

Anabolic Steroids and the Heart

June 12, 2013 By Larry Creswell, MD 8 Comments

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.

Some Thoughts

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.