Thursday, April 19, 2012

The Steroid Effect


          Just when I thought we had reached the end of the Steroid Era, Ryan Bruan, the Milwaukee Brewers’ star left fielder faced a 50 game suspension for violating Major League Baseball’s performance enhancing drug policy. As a Cubs fan, my initial reaction was excitement, as the Brewers face them nearly 20 times per season within the National League Central Division. However, as more and more players fail drug tests, including potential Hall-of-Famers, the sport is becoming tarnished. With the strictest drug policy in sports, minus the Olympics, players still try to beat the system. I find it quite ironic that steroids are now destroying a sport and its athletes, about a decade after saving it and bringing fans back.

During the mid-1990s, Major League Baseball reached a new low in popularity due to a strike-shortened season caused by labor disputes. However, fans quickly returned during the 1998 season when Ken Griffey Jr., Sammy Sosa and Mark McGwire began hitting homeruns at a greater pace than ever before. The league was now as popular as ever because of this new, higher scoring, faster paced style of play.  While this statistic has slowly been on the rise since the sport began, we have never before seen such a drastic increase. To be sure that my mind wasn’t playing tricks on me, I decided to find out exactly how many homeruns were being hit compared to the past. Sure enough, the total had nearly doubled since 1992 when there were approximately 0.7 hit per game, while almost 1.2 were being hit in by the year 2000, as seen in the figure below. Not only were more homeruns being hit, but the average length of them was increasing as well.



This spike in productivity during the late 1990s is probably just a coincidence, right? Wrong! During the 1998 season, a jar of androstenedione (seen in the jmol below), a steroid precursor was discovered in Mark McGwire’s locker. He would later admit that he used the precursors, which helped him to break the single season homerun record, with 70. Unfortunately, at that time, steroids and precursors were not yet banned. Also, famed steroid abuser Jose Canseco came clean in his tell all book “Juiced” during the 2005 season, shortly after rumors began circulating about the allegations around the league. In his book, he ratted out every player that he knew used performance enhancing drugs, leading to a congressional hearing with some of the game’s best. With each player providing short, indirect answers, it could only be assumed that they were silently admitting guilt. Due to the large numbers of accusations and uncertainty, nearly every player who performed at a high level is met with some question. Throughout this process I had no idea how steroids worked, and what they did to the body. Nearly all of the talk suggested that steroids were a good thing, helping players grow to enormous sizes. However, I wanted to know how this unnatural means of muscle growth negatively affected the body as well, specifically on a molecular level.
                                            
                                

After doing some research, I was able to find that anabolic-androgen steroids (AAS) are substances that mimic the effects of testosterone in the body. To put it simply, steroids increase protein synthesis, resulting in increased muscle production and masculinized secondary sexual characteristics. Testosterone enters the cell through the cellular membrane, due to its hydrophobicity, and binds with high affinity to an androgen receptor on the nucleus. Testosterone can also be transformed into dihydrotestosterone, a more active compound, or estradiol, through the catalyzing effects of the enzymes 5-alpha-reductase and aromatase, respectively. The diagram below shows the different possible routes of testosterone after it enters the cell. These compounds bind to receptors as well in a similar fashion. After the formation of the steroid-receptor complex, protein synthesis is stimulated by interaction with RNA and DNA. 5-alpha-reductase activity is found most commonly in male accessory sex glands, skin, the prostate, lungs, brain, fat cells, and bone. Therefore, these organs react more readily to AAS. Conversely, aromatase is more commonly seen in females for the creation of female sex hormones, estradiol and estrone. This enzyme is most commonly found in fat tissue, Leydig and Sertoli tissue, and in some central nervous system nuclei. All of this new information explained the process on a molecular scale, but I also wanted to know what happened on a larger scale. How were these athletes able to build such a ridiculous amount of muscle, so quickly?


The same article explained that AAS-induced increases in muscle mass were caused by muscle hypertrophy and the formation of new muscle fibers. Also, the process of muscle fiber growth seemed to involve the incorporation of satellite cells into existing fibers to maintain constant nucleus to cytoplasm ratios. This allows each fiber to produce the same amount of protein for muscle production per unit volume. Furthermore, certain muscles, but not all, are stimulated to produce more androgen-receptor containing myonuclei. Also, administration of AAS was associated with an increase in satellite cell number, changes in satellite cell ultrastructure, and a proportionate increase in myonuclear number. Recovery time after workout is also decreased. This helps to explain regional differences in body changes. 

Interestingly enough, other growth factors are also involved with the process of hypertrophy. For example, growth hormone (GH) replacement also improves muscle mass in adults, without significant impact on muscle strength. This would support the idea that GH makes athletes larger without improving abilities. However, the key vector for androgen-associated muscle hypertrophy appears to be the satellite cell. The following diagram outlines the different possible outcomes of steroid use, and some of the different molecules involved, leading to muscle hypertrophy. 


After reading about all the positives about steroids, I began to wonder, why don’t all athletes take advantage of these amazing drugs? That’s when I started to read about all the adverse effects caused by steroids. One major, yet obvious effect is seen in the reproductive system. This occurs because exogenous administration of AAS disturbs the body’s production of testosterone and gonadotrophins (LH and FSH). The ladder induces testicular atrophy and reduces semen quality and quantity. This can lead to infertility within months. An additional concern found with steroid abusers is hepatic effects. Liver disturbances and other diseases have been found to be associated with AAS, even in young, healthy athletes. The type most commonly associated with these conditions are 17-alpha-alkylated  steroids such as methyltestosterone, oxymetholone, fluoxymesterone, norethandrolone, and metandienone. While each of these conditions are terrible, there is one in particular that I was interested in exploring: altered mental states/behaviors.            

Case reports have shown that self-administration of AAS is associated with the occurrence of schizophrenia, steroid dependence, affective and psychotic symptoms, and homicide. Other symptoms that have been reported include hypomaniac episodes, violent murder, child abuse, and spousal battery. These cases are most likely attributed to an increase in aggression and hostility, along with mood swings, which are all related to levels of testosterone. Interestingly enough, it has also been shown that many steroid users often do so because of a previously unrecognized lack of self-esteem. Often called reverse anorexia, and later called muscle dysmorphia, these individuals believe they have small, disproportionate bodies that need an increased muscle mass. This pathological preoccupation with their degree of muscularity increases the susceptibility of steroid use. In addition, steroid users possess a narcissistic personality relative to non-users. My source went on to conclude that supratherapeutic doses of AAS may increase muscular strength and lean body mass, leaving endurance performance and fat mass unaffected. This could be why athletes in more cardiovascularly strenuous activities such as running or basketball, refrain from taking part in this activity. 

            With all of this new information at my finger tips, I knew that steroids clearly had a negative impact in the body. Nevertheless, I wanted actual numbers to back up some of the findings. I needed to know to what extent steroids destroyed the body. I was able to find a study that compared different statistics among regular weight lifters, heavy lifters, steroid users, and runners. An effect seen in steroid abusers is increased blood pressure. This could be potentially caused by a larger left ventricular mass, larger posterior wall and larger interventricular septum thickness. Additionally, steroid users experienced a slower recovery in blood pressure after finishing an exercise. However, this appeared to be dose related, as some subjects experienced fewer effects with smaller injections. Finally, steroid users are at a much greater risk for cardiac disease caused by lipoprotein cholesterol. Compared to the other three test groups, steroid users had much higher levels of total cholesterol, LDLs (Low-Density Lipoprotein), and triglycerides. They also had lower levels of high-density lipoproteins, which are considered “good” cholesterol. LDLs are responsible for transporting cholesterol into the artery wall, leading to the formation of plaque, and eventually atherosclerosis, heart attack, stroke, or peripheral vascular disease. Each value that I mentioned can be explicitly found in or inferred from the tables below. 






When I finally came to terms with the idea that most athletes are money hungry cheaters, Ryan Braun’s suspension was overturned. There were alleged problems with the chain of custody of his urine samples, causing them to be invalid and not suitable for testing. Somehow a judge found this excuse to be good enough, even though no seals were broken, and Ryan Braun willingly gave his signature every step of the way. Even with no experts agreeing with his case, the judge believed that the samples could have elevated levels of testosterone just by sitting in a man’s apartment for an extra 48 hours. This was the first time any player had been relieved of a suspension after appealing. I am now forced to watch a likely steroid user tear apart Cubs pitchers, when he really should be suspended. 

Resources
http://www.afboard.com/library/Effects%20of%20Androgenic-Anabolic%20Steroids%20in%20Athletes.pdf
http://jcem.endojournals.org/content/91/1/320
http://www.eje-online.org/content/128/4/313.abstract
http://bjsm.bmj.com/content/37/2/100.full.pdf+html
http://msscentershop.info/content/30/1/11.full.pdf+html
http://milwaukee.brewers.mlb.com/news/article.jspymd=20111210&content_id=26144628&vkey=news_mil&c_i  d=mil
http://www.sabernomics.com/sabernomics/index.php/2006/05/pictures-of-deception/
http://thesteroidera.blogspot.com/2006/08/baseballs-steroid-era-timeline.html
http://joe.endocrinology-journals.org/content/191/2/349.full.pdf+html

1 comment:

  1. These are really helpful information. Steroids are good muscle enhancers, but one has to follow all the precautions to see great effects.


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