Heart Health and Anabolic Steroids
The increasing incidence of unexpected sudden death in certain athlete populations has led to a growing discussion about heart health in sports.
Heart disease is the leading cause of sudden death in both the general population and athletes [1].
Given that the athlete population is constantly engaged in strenuous physical activity, it is commonly assumed that their heart health is optimal.
While this may be generally true, the use of performance-enhancing drugs (PEDs) can skew health outcomes in this population.
The types of PEDs used by athletes vary greatly by sport.
They include anabolic androgenic steroids (AAS), peptide hormones, stimulants, erythropoietin (EPO), and other drugs.
Many of the unexpected deaths that have occurred over the past decade have been among people competing in sports where AAS use is prominent.
These sports are also characterized by the abuse (high-dose use) of these agents, among many others.
The purpose of this article is to evaluate AAS use in athletes in the context of cardiac health and other confounding variables.
Sudden cardiac death and differential diagnosis
The most common cause of sudden cardiac death in the general population is fatal arrhythmias due to coronary artery disease (CAD).
Similarly, older athletes with risk factors for CAD are at increased risk of developing ischemic heart disease, which can lead to dangerous and fatal arrhythmias [2].
Younger athletes can also be at risk for fatal arrhythmias if they have congenital risk factors.
Unlike older athletes, where acquired CAD is more prevalent, younger athletes rarely experience the same conditions, with the exception of coronary artery spasms and vasculitis.
It is important to note that the most common final cause of fatal heart disease is ventricular fibrillation, or pulseless electrical activity.
While CAD is the most common pathologic cause of fatal arrhythmias, there are many different causes to consider.
Acquired Structural Heart Disease
Coronary artery disease/atherosclerosis
Left ventricular hypertrophy (LVH)
Mitral valve prolapse (MVP)
Dilated cardiomyopathy
Myocarditis
Congenital structural heart disease
Hypertrophic obstructive cardiomyopathy (HOCM)
Coronary artery abnormalities
Left ventricular noncompaction
Dilated cardiomyopathy
Arrhythmogenic right ventricular dysplasia
Congenital aortic stenosis
Congenital electrophysiologic disorders
Long QT syndrome
Short QT syndrome
Catecholaminergic polymorphic ventricular tachycardia (CPVT)
Wolff-Parkinson-White syndrome
Brugada syndrome
Idiopathic ventricular tachycardia
Mixed sodium channel disease
Atrioventricular block
These various acute events, structural problems, and electrophysiologic defects can lead to unstable and potentially fatal arrhythmias.
Understanding the various causes of sudden cardiac death is important to provide clinical context for PED-induced cardiac arrest.
Therefore, the clinical conditions in bold highlight potential causes of sudden cardiac death in athletes [4].
While certain acute causes (e.g., trauma or aortic rupture) may be secondary, other causes are typically self-induced.
Electrolyte changes, such as hypokalemia, can be caused by diuretic abuse.
Hypoglycemia can be caused by improper insulin use.
In addition, stimulant overdose can cause unstable tachycardia.
We'll discuss other acquired conditions in more detail in this article, but it's important to understand that all of the other conditions listed can increase the risk of heart disease over a long athletic career.
This occurs independently of PED use, so abusing PEDs in the presence of a pre-existing (or unknown) heart condition can further increase your risk.
Performance-enhancing drugs and heart attacks
There are several long-term mechanisms that can increase the risk of sudden cardiac death in PED users.
These cardiac mechanisms can be categorized as direct structural changes, indirect structural changes, arrhythmogenic, and atherosclerotic disease.
While the use of AAS is primarily related to these potential changes, there are confounding variables that are often underestimated. These include peptide hormones, stimulants, and diuretics.
It is important to note that while peptide hormones (e.g., human growth hormone) may play an important role in cardiac structural changes, the use of stimulants and diuretics can be variables that contribute to heart disease as previously mentioned.
Direct structural changes
The use of AAS has been extensively linked to left ventricular hypertrophy in the literature.
These hormones bind to myocardial androgen receptors in the heart and induce sustained growth.
Certain agents, such as testosterone, induce less significant growth.
Other agents, such as trenbolone, cause severe LVH in the long term.
A significant portion of LVH growth can also be attributed to intensive exercise, but the mechanism is different from AAS-induced LVH growth.
Concurrent use of certain peptide hormones, which is relatively common, is another major factor in left ventricular growth.
Unfortunately, most evidence suggests that these changes are irreversible with long-term abuse [5][6].
The pathologic state of left ventricular hypertrophy typically means that enlarged cardiomyocytes are not accompanied by a relatively uniform increase in capillaries.
This results in a mismatch in oxygen and nutrient supply compared to demand.
In addition, cardiomyocyte death can occur, along with changes in intracellular calcium.
The clinical consequences of increased oxygen and metabolic demands, along with other microscopic changes, can lead to decompensation and heart failure.
Indirect structural changes
Elevated blood pressure is the most common cause of LVH in the general population and is a major antecedent clinical factor leading to heart failure [7].
Anabolic steroids exhibit hypertensive effects depending on the specific agent.
Oral steroids that cause extensive water retention are generally more hypertensive than agents that cause minimal water retention.
Certain steroids have vasoconstrictor effects and can inhibit natriuretic peptides, which can cause hypertension.
These effects are amplified by long-term use of stimulants/pre-workout supplements that directly increase blood pressure.
Similarly, thyroid medications and clenbuterol used for fat loss also contribute significantly to a persistent hypertensive state. In summary, these hypertensive effects contribute to the chronic and often irreversible LVH seen in many AAS users [8].
Arrhythmias
Fatal arrhythmias are the end result before complete cardiac arrest, but there is no significant evidence that AASs can directly cause arrhythmias.
One study has shown prolongation of certain electrophysiologic variables, including QTc, JTc, and Tp-e/QTc.
However, it is difficult to link these changes to an increased risk of ventricular tachycardia [9].
It is worth noting that the dose of testosterone replacement therapy used to normalize testosterone is associated with a reduced incidence of atrial fibrillation [10].
The main variables that can cause arrhythmias in athletes are stimulants and stimulants and diuretics. In athletes with significant structural damage to the heart, arrhythmias can be triggered by increased strain on the heart or suboptimal conditions.
Increased stimulation directly increases heart rate and contractile force, which increases cardiac oxygen demand.
This can then lead to ectopic and irregular heart rhythms.
In addition, the use of diuretics can cause electrolyte changes.
Potassium, magnesium, and calcium are particularly important electrolytes. Hypokalemia, hypocalcemia, and hypomagnesemia increase the tendency for dangerous arrhythmias.
Atherosclerosis
The leading cause of sudden cardiac death in humans is atherosclerotic coronary artery disease.
This disease is caused by years of poorly managed lipid profiles and other risk factors.
Anabolic steroids have been shown to be strongly associated with a decrease in high-density lipoprotein (HDL), a mild to moderate increase in low-density lipoprotein (LDL), and changes in overall cholesterol levels.
One mechanism is that AASs can break down lipoproteins and alter apolipoprotein A-I and B synthesis.
This dysregulated lipid profile leads to the formation of plaque inside the arteries and a long-term risk of ischemic heart disease.
It is important not to ignore other lifestyle factors, such as smoking, which play an important role in this pathological process [11].
Finally, heavy use of aromatase inhibitors (AIs) in combination with AAS leads to a decrease in estradiol to varying degrees.
This can directly worsen the lipid profile, often to a significant degree.
There are also other confounding factors associated with AAS that affect the outcome of atherosclerosis.
One relatively common effect of anabolic steroids is an increase in hemoglobin and hematocrit levels, resulting in polycythemia.
Increased blood viscosity, if severe enough, can induce platelet aggregation, which can increase the risk of ischemic heart disease. Kidney disease is another variable, with focal segmental glomerulosclerosis[12] and cardiorenal syndrome, particularly due to trenbolone, becoming increasingly prominent in AAS users.
Deterioration of the renal system has a significant adverse effect on the cardiac system.
Solutions and preventative measures
Because the earliest symptom of heart disease is sudden death, the best treatment for heart disease is to prevent the disease itself.
Given the categories of AAS-induced heart disease described earlier, these pathologic processes often overlap and require comprehensive management.
It is essential to take a detailed medical history and perform a physical examination to properly assess the cardiovascular system.
The patient should also be screened for a history of syncope, presyncope, chest pain, shortness of breath, or increased difficulty with exertion.
When it comes to heart health, patients should have their lipid profile, complete blood count (CBC), chemistry panel, and kidney function closely monitored (among other lab tests).
The frequency of testing is controversial, but every two years is recommended.
As mentioned earlier, it is very common for lipid profiles to become distorted while using AAS.
If HDL-lowering and/or LDL-raising levels are recorded, it is recommended to start statin therapy.
The medical community is hesitant to start statin therapy in some younger patients in this category, but if anabolic steroids are not stopped, the patient is at increased risk for atherosclerosis.
Statins also have a therapeutic effect on the coronary arteries themselves.
However, taking statins depletes coenzyme Q10 levels.
Therefore, supplementation is a reasonable option [13].
Other treatment options have mixed efficacy for lipid control.
The main exception is PCSK9 inhibitors, but while AAS are known to primarily affect HDL, they may not be as beneficial because of their very strong effect on LDL.
Other supplements that may improve lipid profiles include omega 3s and high-dose garlic [14][15].
The literature consistently shows some improvement in HDL levels after omega 3 intake and LDL levels after high-dose garlic supplementation.
Garlic may also reduce the likelihood of side effects from increased blood viscosity.
The use of other supplements, such as niacin (which may be prescribed for this purpose), is controversial.
Treating AAS-induced hypertension can present some challenges.
In these situations, the first line of treatment is always to stop taking the offending drug.
This requires proper counseling, and the patient should be advised to stop the specific medication that is causing the hypertension.
Certain oral steroids that induce excessive water retention (e.g., Dianabol) and certain other injectables with key hypertensive properties (e.g., Trenbolone) are often the culprits.
Because these oral agents are taken periodically for short periods of time, they are less of a concern than medications with hypertensive effects.
In addition, continued use of non-caffeinated stimulants should be discontinued, and patients should be advised to use caffeine only in reduced doses.
In addition to stopping the offending medication, it is often essential to start medication to lower blood pressure.
While standard guidelines can be utilized for blood pressure management, it is important to take an accurate medical history when considering the use of diuretics in some AAS users.
For some patients, prescribing an ACE inhibitor or ARB medication is very useful not only to control blood pressure, but also to prevent/reduce left ventricular hypertrophy.
However, depending on ethnicity, ACE/ARB medications may not be well tolerated for blood pressure control; therefore, beta blockers and calcium channel blockers are another potential option.
It is worth noting that beta blockers may provide additional benefits for some AAS users.
If you have pre-existing left ventricular dilatation, beta blockers may improve coronary perfusion and lower the risk of arrhythmias.
In addition to medications, taking supplements can also be helpful.
Garlic can lower blood pressure in addition to its beneficial effects on lipids [14].
Other supplements may intermittently improve blood pressure, but the evidence for their effectiveness is very weak.
And as far as lifestyle factors are concerned, AAS users already have optimal dietary habits and get enough exercise.
The diagnosis and management of left ventricular hypertrophy presents numerous challenges for clinicians.
However, given that left ventricular hypertrophy is a likely cause of sudden death in AAS users, appropriate attention is warranted.
Diagnosing pathologic left ventricular hypertrophy can be challenging because athletes typically experience physiologic levels of left ventricular hypertrophy due to intensive exercise.
The primary mode of cardiac screening is the electrocardiogram (ECG), but the medical community is generally hesitant to perform ECGs extensively.
This is due to the risk of false positives, which can lead to unnecessary testing.
However, in the athlete population, the Seattle criteria have provided a methodology that can be used to perform screening ECGs with minimal false positives.
For ventricular fibrillation (LVH), the Cornell or Sokolow-Lyon voltage criteria or the Romhildt-Estes point system were used.
Interestingly, one aspect of the Seattle criteria is that a positive electrocardiogram for LVH in athletes should be ignored.
Regardless of which criteria are used, clinical judgment should be used [16].
The most reliable and common way to diagnose LVH is by echocardiography.
However, it is impractical to perform echocardiography on all AAS users for obvious reasons.
Therefore, clinicians need to be selective about potential test subjects.
Common things to look for include a very long history of AAS use, concomitant hypertension, extensive use of peptide hormones, and use of certain agents known to cause LVH (e.g., Winstrol).
Overall, most AAS users should not undergo echocardiography unless several key risk factors and/or symptoms are identified.
Once screening is complete, specific markers can be used to differentiate between physiologic and pathologic LVH.
Left ventricular wall thickness greater than 15 mm is diagnosed as pathologic LVH, whereas 11 mm or less is completely normal.
Physiologic left ventricular wall thickness is typically within 11 to 13 mm, with 13 to 15 mm being a "gray area" that requires further evaluation [17].
Once a diagnosis of pathologic LVH is made, it is essential to first discontinue the offending medication and control the patient's blood pressure.
Second, consideration should be given to prescribing ACE/ARB medications and/or beta-blockers, as discussed previously.
These block the cardiomyocyte growth factor angiotensin II, which regresses the actual LVH and concentric remodeling itself. In addition, severe LVH increases the risk of ventricular tachycardia, and the use of beta-blockers can lower the risk of arrhythmias while controlling blood pressure and improving coronary perfusion [18].
Overall, the clinical challenge of preventing and treating heart disease in athletes depends on numerous variables, especially in the context of PED use.
Identifying congenital issues is the most important background issue, as intense exercise in combination with PEDs can exacerbate pre-existing pathologies.
It is also important to prevent PED-induced heart disease, so counseling along with proper screening is essential.
Any identified issues should be treated early to prevent long-term risks.
Achieving optimal results for athletes is a byproduct of a good doctor-patient relationship.
SOURCE: Medically reviewed and prepared by Dr. Khash Farzam on June 5, 2019, based on data from
DISCLAIMER
Dr. Khash Farzam's content is for academic and educational purposes only.
None of the content should be taken as any form of medical advice under any circumstances.
Dr. Khash Farzam does not support or endorse the use of any form of medication, drug, or supplement that is not prescribed and supervised by an individual's physician.
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