Dr Laura C Sommerfeld, Dr Andrew P Holmes and Professor Larissa Fabritz
Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK
& University Center of Cardiovascular Science, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Our genetic architecture influences the stability of our heart muscle. A few changes to the blueprint could disrupt this stability, increasing the risk of developing heart conditions. Research published in The Journal of Physiology by a team of clinicians and researchers from the University of Birmingham, UK and University Medical Center Hamburg-Eppendorf, Germany, explores the genetic composition of the heart to understand how differences could have dangerous outcomes for people misusing anabolic steroids to build muscle. Furthermore, the increased risk of heart conditions and vulnerability to steroids may not be equal between males and females.
In this blog, the researchers explain how the trend in anabolic steroid misuse has increased with the rise of fitness influencers on social media, heightening the need to understand the risk of the drug for underlying heart conditions that many could be unaware of.
What are anabolic steroids?
The male sex hormone, testosterone and its breakdown product dihydrotestosterone (DHT), are produced naturally in the body. The structure of these hormones has been used to create a class of drugs, called androgenic anabolic steroids (AAS), which promote muscle growth and develop male sexual characteristics. AAS can be prescribed as testosterone replacement therapy (TRT) by medical professionals to restore AAS to normal levels in individuals who don’t make enough of their own.
In addition to their regulated therapeutic use, anabolic steroids are widely misused, predominantly by young men, to increase muscle mass, reduce fat, improve athletic performance and change cosmetic appearance. In these instances, the drugs are obtained through peers, the internet and social media, and are self-administered (via injection into muscles or oral delivery) to achieve very high levels in the blood.
The rise of the social media fitness influencer and steroids
Estimates suggest that 1-5% of people worldwide will use anabolic steroids at some point in their lifetime, however this may be significantly higher in certain groups such as elite male athletes and gym goers. With the rapid emergence of social media fitness influencers, more and more young people might feel the need to become stronger and change their appearance. Some social media influencers may even encourage the use of anabolic steroids to their followers. As such, it is likely that the number of people who misuse the drug could increase in the future.
There are many reports emphasising that high levels of anabolic steroids can have dangerous effects on the heart. However, few studies have explored why some individuals may be at higher risk of developing serious heart problems upon taking anabolic steroids than others. One potential avenue being explored is genetic differences between people. Identifying those most vulnerable to anabolic steroids based on key genetic differences should help with risk prevention and improve clinical outcomes.
Faulty wiring and electrical problems in the heart
Studies suggest that several heart rhythm disorders are more likely to occur in men than women. In our study, we wanted to test if the same was true for arrhythmogenic right ventricular cardiomyopathy (ARVC) and atrial fibrillation (AF), which would implicate that anabolic steroids may increase the risk for men. ARVC is an inherited genetic disorder affecting the connections between the cells in the heart. In the worst circumstances, people with ARVC can experience massive loss of cardiac electrical integrity leading to sudden cardiac death. In our study, we were interested in assessing whether key genetic mutations associated with ARVC increase the risk of developing electrical problems in the heart upon taking anabolic steroids.
Comparing the clinical data
We initially analysed clinical data for 146 patients with ARVC to compare the incidence of the disease between male and females, and to determine if ARVC increased the risk of developing other heart rhythm problems, such as AF. Our human data shows that men are more likely to have ARVC than women. In males with ARVC, there was also a strong likelihood of developing atrial fibrillation (AF).
Graphical abstract of the research. It shows the observations from the clinical analysis, and highlights the experimental set-up and key changes in cardiac function using the mouse model.
Using a model to find mutations in the genetic foundation
Using a genetically altered mouse model of ARVC (plako+/-), we explored if male mice exposed to anabolic steroids for six-weeks produced greater changes in the electrical properties of the atria (the two upper chambers of the heart). We compared the results between young male mice with the plako+/- atria mutation to the mice without this mutation (the control group).
In the mouse experiments, exposure to anabolic steroids caused similar changes in cardiac inflammation, growth and fibrosis in control and plako+/- atria. However, the drug produced more severe electrical dysfunction in the atria of the plako+/- mice, suggesting enhanced risk. Key changes in the plako+/- atria mice exposed to anabolic steroids included exaggerated alterations of the ECG, a significantly slower rate of electrical conduction, more severe depression of electrical currents and greater disorganisation of ion channels. Interestingly, the changes on the ECG that we saw in plako+/- mice exposed to anabolic steroids were similar to those observed in male patients who had ARVC, suggestive of a shared mechanism.
One´s genetic makeup can increase the risk of developing heart rhythm disorders with taking anabolic steroids
The exaggerated electrical changes observed in the atria of ARVC (plako+/-) male mice show that hearts with ARVC-associated genetic mutations are more vulnerable to electrical remodelling upon taking anabolic steroids. Therefore, we suggest that young males with ARVC related genetic mutations are likely to be at a higher risk of developing cardiac electrical problems leading to heart rhythm disorders, such as AF, if they misuse anabolic steroids.
Steroids could trigger underlying heart conditions
Our study is one of the first studies to show that key genetic mutations enhance the risk of heart disease when taking anabolic steroids. Our work focused on evaluating the impact of anabolic steroids on atrial electrical changes in mice with ARVC mutations, but we may have only captured the relatively early stages of cardiac electrical remodelling. We tested the drug response using a short period of six-weeks and assume that the electrical remodelling could be more severe when anabolic steroids are used for longer periods.
Further research is needed to test the findings presented in our mouse model. Clinical research by other groups already confirms increased risk of males with higher testosterone levels for complications of heart disease including ARVC. It is likely that there are other relevant gene mutations/variants that will moderate individual sensitivity to anabolic steroids both in the heart and other organs. More genetic screening could be done to identify those who would be most vulnerable to developing heart rhythm problems. Misuse of anabolic steroids comes with considerable risks and should be avoided.
Read the full paper published in The Journal of Physiology.