Please enjoy this post from the archives dated, April 17, 2013
By David G. Rosenthal and Robert Gianotti, MD
Faculty Peer Reviewed
Case: A 33-year-old man comes to your clinic complaining of worsening acne over the last 6 months. You note a significant increase in both BMI and bicep circumference. After several minutes of denial, he reveals that he has been using both injectable and oral anabolic steroids. He receives these drugs from a local supplier and via the Internet. He confides that his libido has dramatically increased and he feels increasingly pressured at work, describing several recent altercations. He admits that these symptoms are a small price to pay for the amazing performance gains he has seen at the gym. He plans to compete in a local deadlifting tournament at the end of the month. He asks you if he is at increased risk for any health problems and whether short-term use is associated with any long-term consequences. You quickly realize that you have no idea what literature exists on the health consequences of anabolic steroids. Fortunately, you have set the homepage on your web browser to Clinical Correlations. Together, you read…
The recreational use of anabolic steroids has drawn increasing international attention over the last decade due to their use and abuse by athletes and bodybuilders. Athletes including Arnold Schwarzenegger, cyclist Lance Armstrong, baseball slugger Mark McGuire, and Olympic gold medal sprinter Marion Jones have all come under scrutiny for using steroids to gain a competitive advantage and shatter records. In fact, the 1990’s are notoriously known in Major League Baseball as the “Steroids Era.” Critics argue that the use of these substances contradicts the nature of competition and are dangerous given the abundance of reported side effects. Accordingly, the vast majority of sporting associations have banned the use of anabolic steroids, and their possession without a prescription is illegal in the United States, punishable by up to one year in prison. Nevertheless, the performance-enhancing, aesthetic, and financial benefits of anabolic steroids has led to rampant abuse by both professional and high school athletes with an astonishing 3.9% of students having tried anabolic steroids at least once during high school 1, 2.
Anabolic steroids are synthetic derivatives of testosterone, the primary male sex hormone. Androgenic effects of testosterone include maturation of secondary sex characteristics in both males and females, development of typical hair patterns, and prostate enlargement, while its anabolic effects include strength gains and bone maturation via regulation of protein metabolism 3. Administration of exogenous testosterone causes upregulation of the androgen receptor in skeletal muscle, resulting in increased muscle fiber size and number 4. Anabolic steroids can be absorbed directly into skin, injected, or taken orally. Synthetic oral steroids, including methyltestosterone and fluoxymesterone, are 17-alpha alkylated which prevents first-pass metabolism by the liver and may contribute to increased hepatotoxicity 5.
Much of the public opinion about anabolic steroids has been obtained from individual testimonies and well-publicized user narratives. While thousands of articles have been published in scientific journals describing both the desired and adverse effects of anabolic steroid abuse, a number of these studies have drawn questionable conclusions due to flawed methodologies, inadequate sample sizes, study biases, and most importantly the inability to replicate the actual drug dosages used by many athletes. The regimens of many steroid users often consist of twenty-fold higher concentrations than have been previously examined in the literature 6. Hence, the precise effects of the supraphysiologic doses of steroids that are commonly abused may never be known.
Strength, endurance and reduced recovery time are all attributes that the competitive athlete strives to obtain. Historically, institutions and even governments have dabbled in performance enhancement for competitive athletes. It has been well documented that Communist-era East Germany sought to build superior athletes to compete in the Olympic Games and flex their muscles on the world stage. Documents studying the effects of anabolic steroids, including oral Turinabol on Olympic athletes in East Germany from 1968-1972 showed remarkable improvements in strength sports: Discus throws increased by 11-20 meters; shot put distance improved by 4.5-5 meters; hammer throw increased by 6-10 meters; and javelin throw increased 8-15 meters 7. The strength gains among East German female athletes were most notable, as were the side effects including hirsutism, amenorrhea, severe acne, and voice deepening. In fact, when a rival coach commented on the voice changes of the competitors, the East German coach responded “We came here to swim, not sing”8. Following the implementation of “off-season” steroid screening by the International Olympic Committee and other competitive organizations in 1989, track and field sports saw a dramatic reduction in performance. Notably, the longest javelin throw by a female in the 1996 Olympics was 35 feet shorter than the world record of 1988.
The gains seen with anabolic steroid use extend beyond the Olympic athlete to recreational body-builders and gym-rats. In a small placebo controlled study from the Netherlands, a ten-week course of injectable nadrolone in a cohort of recreational body builders increased lean body mass by an average of 2-5 kg, with no accompanying increase in fat mass or fluid retention 9. These effects persisted for more than 6 weeks after the cessation of nandrolone. Surprisingly, performance enhancement can be seen with anabolic steroids even in the absence of exercise. In fact, one study including healthy, young men between the ages of 18 and 35 who had endogenous androgen production suppressed with GnRH showed that supraphysiologic doses of testosterone enanthate administered for 20 weeks caused a 15% dose dependent increase in muscle size and a 20% increase in muscle strength without any exercise 10. This study came as a logical follow up to a smaller study published in the New England Journal of Medicine in 1996 that showed impressive performance gains compared to placebo among both exercising and sedentary subgroups. At 10 weeks, the testosterone + exercise group was able to bench press a mean of 10kg more than both the testosterone alone and exercise alone subgroups11.
The performance gains from steroids have also been shown to extend into the eighth and ninth decades of life. A 2003 study in men aged 65-80 showed significant gains compared to placebo in both lean body mass and single repetition chest press after receiving either 50mg or 100mg of the orally bioavailable steroid, oxymethalone. The men in the 100mg group were able to chest press 13.9% +/- 8.1% (p<0.03) compared to placebo and had a 4.2 +/- 2.4 kg (p<0.001) increase in lean body mass 12. Many athletes also report that anabolic steroids increase endurance and decrease recovery time after workouts. This has been supported in the literature where indirect measures of fatigue, such as increased serum lactate and elevated heart rate were delayed after the injection of nandrolone decanoate with a notable improvement in recovery time4.
We now know from a small, but significant pool of data that the performance gains from anabolic steroids are real and can be seen not only in elite athletes but casual users as well. The existing data regarding the side effects of anabolic steroid is varied and relies heavily on self-reported outcomes and dosing regimens that are often variable and combine multiple unique drugs.
One method of obtaining data regarding the adverse effects of anabolic steroid abuse is by employing questionnaires. While this method is inherently biased, it may the only way to obtain data from subjects using very high doses that are considered unsafe or unethical for higher quality studies. Regardless of the method of data collection, it has been well established that up to 40% of male and 90% of female steroid users self-report adverse side effects including aggression, depression, increased sexual drive, fluid retention, hypertension, hair loss, and gynecomastia4. Other reported side effects include: increased levels of the hormone erythropoietin leading to an increased red blood cell count; vocal cord enlargement, leading to voice deepening; and increased risk of sleep apnea.
Exogenous administration of steroids can have immediate and profound effects on the reproductive system, largely mediated through disruption of the hypothalamic-pituitary-adrenal-gonadal axis. Within 24 hours of use, steroids cause a dramatic decrease in follicle stimulating hormone and luteinizing hormone, which can result in azospermia in males and menstrual irregularities in females within weeks, and infertility within months 13, 14. Supraphysiologic testosterone concentrations result in virilization of females, which is characterized by hirsutism, clitoromegaly, amenorrhea, and voice deepening 15. When steroids are abused for longer periods of time, men can suffer from hypogonadotropic hypogonadism, manifested by testicular atrophy, as well as gynecomastia due to peripheral conversion of the exogenous testosterone to estrogen 15. Some athletes try to increase their sperm count by using human chorionic gonadotropin or clomiphene, both commonly used female fertility drugs, but the efficacy of these hormones are debated; moreover, they do not reduce gynecomastia4. Commonly, drugs such as Propecia, routinely used to treat male-pattern baldness and benign prostatic hypertrophy, are used to increase testosterone levels. Although there have been reports of prostatic hypertrophy in steroid users, there is no known associated risk with the development of prostate adenocarcinoma 16, 17.
Adverse cardiovascular outcomes in steroid abusers have been published, including cardiomyopathy, arrhythmia, stroke, and sudden cardiac death18. However, causation has often been inappropriately attributed solely to anabolic steroid use and the data can be misleading due to confounding variables and study biases 4. The structural, functional, and chemical changes associated with steroid abuse are crucial to consider because many of the reported effects are independent risk factors for cardiovascular disease.
A study published in Circulation in 2010 evaluated left ventricular function in a cohort of weightlifters (n=12) with self-reported anabolic steroid use compared to age-matched weightlifting controls (n=7). After adjusting for body surface area and exercise, the investigators found a significant reduction in left ventricular systolic function (EF= 50.6% vs. 59.1%, p=0.003) 19, and the association remained statistically significant even after controlling for prior drug use including alcohol and cocaine. Interestingly, there appeared to be no relationship between cumulative anabolic steroid use and ventricular dysfunction, although the authors note limitations due to small sample size and the bias of self reported data.
Other studies investigating cardiovascular outcomes of anabolic steroid suggest a transient increase in both systolic and diastolic blood pressure in steroid users, although these values return to baseline within weeks of cessation 20. In addition, long term use of anabolic steroids can lead to increased platelet aggregation, possibly contributing to increased risk for myocardial infarction and cerebrovascular events 18.
Anabolic steroids cause a variable increase in LDL and up to a 40-70% decrease in HDL, often resulting in the misleading finding that steroids do not affect total plasma cholesterol 21. Fortunately, these effects are reversible within 3 months of cessation of the agent 22. The use of the 17-alpha-alkylated steroids can cause a 40% reduction in apolipoprotein A-1, a major component of HDL, while an injectable testosterone has been shown to have a tempered 8% reduction 23. Although these effects are reversible with cessation, they underscore the importance of screening anabolic steroid users for lipid abnormalities.
Steroid use has been linked with a number of hepatic diseases. The use of oral steroids is associated with a transient increase in transaminase levels, although some data suggest that this may be due to muscle damage from bodybuilding rather than from liver damage 24. The link between 17-alpha-alkylated steroids and hepatomas, peliosis hepatis (a rare vascular phenomenon resulting in multiple blood filled cavities within the liver), and hepatocellular carcinoma has been suggested in case studies, but no causal relationship has been established 25.
Possibly the most publicized adverse effect of steroid use is psychological, publicly coined “roid rage.” In one study using self-reported data, 23% of steroid users acknowledged major mood symptoms, including depression, mania, and psychosis 26. However, most studies report only subtle psychiatric alterations in the majority of patients, with few patients experiencing significant mood disorders 27. However, a 2006 cohort study from Greece found a dose dependent association between steroid use and psychopathology that was driven by significant increases in hostility, aggression and paranoia (P<0.001) 28. While this topic needs further research, it does lend credence to the theory that “’roid rage” exists, and its effects are exacerbated by higher doses of steroids.
Conclusion:
The former baseball all-star Jose Canseco once claimed that “steroids, used correctly, will not only make you stronger and sexier, they will also make you healthier 29.” Although current research reveals that steroid abuse is not independently associated with increased mortality 16, and many of the adverse effects are rare and reversible with cessation of use, there is a dearth of knowledge about the effects of the actual regimens used, and the long-term side effects of these drugs are largely unknown.
Based on the paucity of quality data and frightening implications of metabolic derangements, heart failure, and infertility, your patient leaves convinced that he has made a poor decision in choosing to use anabolic steroids. He pledges to quit immediately and defer competing in the deadlifting tournament until next year after a “washout” period. He is eager to disseminate his new found knowledge at the local gym, but not before he makes a stop at GNC to load up on creatinine supplements and whey protein.
David G. Rosenthal is a 4th year medical student at NYU Langone Medical Center and Robert Gianotti, MD is Associate Editor, Clinical Correlations
Peer reviewed by Loren Greene , MD, Clinical Associate Professor, Department of Medicine (endocrine division) and Obstetrics and Gynecology
Image Courtesy of Wikimedia Commons
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