How do they work? How are they detected? What are their risks?
During the 2024 Paris Olympics, the global sports community centered their attention on the World Anti-Doping Agency because of allegations that twenty-three Chinese swimmers used the performance-enhancing drug trimetazidine (TMZ), a drug which reduces oxygen consumption and improves cardiac function. This case highlights a broader issue in sports: many athletes, driven by the desire to win, often turn to performance-enhancing drugs (PEDs) for a competitive edge. The use of these drugs is known as doping, a widespread phenomenon that plagues not only top athletes, but also amateurs and school-age children (1). So, what exactly makes these drugs so effective and popular?
The main PEDs athletes use are anabolic steroids, which are synthetic versions of testosterone (a kind of androgen, hormones that regulate development of male characteristics). Testosterone is a naturally produced hormone in leydig cells that has many desirable effects on the body, such as increasing muscle strength, bone density, and red blood cell production (2). Its synthetic version can be administered orally, via intramuscular injection, or through gels and creams (3).
Testosterone activates satellite cells, those responsible for the growth and repair of skeletal cells. When existing myonuclei (muscle fiber nuclei) can no longer sustain additional protein synthesis, testosterone also promotes the formation of new myonuclei. Additionally, testosterone encourages pluripotent precursor cells (those that can develop into different types) to form myotubes (mature skeletal cells). Beyond muscle growth, testosterone also inhibits fat cell development, acting through androgen receptors in myonuclei and satellite cells and possibly through other pathways (3).
Chemical structure of testosterone.
This process begins with testosterone first binding to an androgen receptor (AR), which are proteins that allow the body to respond to androgens like testosterone. Together, the testosterone-AR complex travels to the cell’s nucleus and binds to specific DNA sequences called androgen response elements. This leads to the upregulation of genes involved in muscle growth and recovery, increasing contractile protein synthesis and muscle hypertrophy (3).
Research has identified key mechanisms behind the significant myotrophic effects of testosterone in high-level powerlifters who used testosterone (100–500 mg per week) for an average of 9 years. Evidence indicates that the most significant difference in muscle fiber size between steroid users and non-users occurs in slow type I muscle fibers (3).
In the trapezius muscle of steroid users, type I muscle fiber areas are 58% larger than non-users, while type II fibers are 33% larger. A similar pattern is observed in the vastus lateralis, a thigh muscle. Research shows that type I muscle fibers respond more to anabolic agents than type II fibers. Additionally, administering 300 mg and 600 mg of testosterone increases the area of type I fibers, while type II fibers only show enlargement after receiving 600 mg of testosterone (3). This can reap advantageous benefits for the user, as type I muscle fibers are used for endurance activities, and type II muscle fibers are used for short, quick bursts of energy.
Detecting testosterone doping is challenging because the hormone is also produced naturally in the body. Thus, the primary concern in doping control is determining the source of testosterone present in human urine. The urinary testosterone to epitestosterone (T/E) ratio can be used as an indirect test for testosterone doping (3). This test works because the T/E ratio in a healthy human is 1:1, and using anabolic steroids only increases the testosterone amount.
If an athlete’s T/E ratio exceeds 4:1, further testing is done using gas chromatography to measure the Carbon-13/Carbon-12 ratio. The two main isotopes of carbon found in nature are Carbon-12 and Carbon-13, which both have the same amount of neutrons but different amounts of protons. Carbon-12 is much more common, making up about 98.9% of all carbon atoms, while Carbon-13 is rarer, accounting for about 1.1%. Despite their different masses, these isotopes behave the same chemically, meaning they form bonds and participate in reactions in the same way. This method works as external testosterone generally contains less Carbon-13 than naturally produced testosterone (3).
PEDs can result in a large amount of side effects, including hypertension, leukemia, infertility, “Roid Rage,” and much more (4). One primary risk is polycythemia, when testosterone is artificially added to the body (5). This is because an excess of testosterone can cause increased red blood cell production, and although athletes typically want this, too much can make it harder for blood to circulate throughout the body. This results in an increased risk of high blood pressure, blood clots, stroke, and heart attacks (5). Additionally, continued use of PEDs can cause the target hormone to stop being produced naturally, causing organ enlargement, which can result in liver damage and other side effects.
Psychological side effects can also occur, as testosterone is often linked to increased aggressiveness due to its effects on subcortical brain structures such as the amygdala and hypothalamus. Like other anabolic steroids, discontinuing testosterone use may lead to depression and, in severe cases, even suicidal thoughts or actions (5).
PEDs are most prevalent in sports like cycling, which has the most doping cases with 3.6% of positive test results, followed by weightlifting at 3.0%, boxing at 2.9%, triathlon at 2.7%, and baseball at 2.5% (6). From this information, we can see that sports like cycling, boxing, and triathlons are based on extreme endurance, and weightlifting and baseball are based on extremely quick, explosive power, which is likely why doping cases are so common in them.
Despite boosting an athlete’s performance, PEDs, particularly anabolic steroids, are strictly banned from many professional sports and pose significant health risks. These substances can lead to severe long-term health consequences, including cardiovascular disease, liver damage, hormonal imbalances, and mental health issues such as depression and aggression. Moreover, they create an unfair playing field and undermine the integrity of sports, where victory should be earned through natural talent and hard work. Allowing doping to continue would not only endanger athletes’ lives but could also erode public trust in sports, turning competition into a race of who can cheat better. Thus, it is a moral imperative to intensify anti-doping efforts to prevent injuring athletes and protect the integrity of sports.
Sources:
- Mayo Clinic. (2023). Learn about the risks of performance-enhancing drugs. Retrieved from https://www.mayoclinic.org/healthy-lifestyle/fitness/in-depth/performance-enhancing-drugs/art-20046134
- Baum, Z. (2021, July 21). The science behind performance-enhancing drugs. CAS. Retrieved from https://www.cas.org/resources/cas-insights/science-behind-performance-enhancing-drugs
- Kadi, F. (2008). Cellular and molecular mechanisms responsible for the action of testosterone on human skeletal muscle: A basis for illegal performance enhancement. British Journal of Pharmacology, 154 (3), 522–28. https://doi.org/10.1038/bjp.2008.118
- U.S. Anti-Doping Agency (USADA). (2019, May). Effects of performance-enhancing drugs. Retrieved from https://www.usada.org/athletes/substances/effects-of-performance-enhancing-drugs/
- Srakocic, S. (2024, April 15). What’s the link between testosterone and polycythemia? Healthline. Retrieved from https://www.healthline.com/health/low-testosterone/polycythemia-testosterone#understanding-risk
- Sullivan, P. (2013, June 29). What sports have the worst doping problems? Foreign Policy. Retrieved from https://foreignpolicy.com/2013/06/29/what-sports-have-the-worst-doping-problems/
Images: