aNortheastern Ohio Universities College of Medicine, 4209 State Route 44, PO Box 95, bDivision of Sports Medicine, Akron Children’s Hospital, Sports Medicine Center, 388 South Main Street, Suite 207, Akron, OH 44311, USA The ‘‘win at all costs’’ mentality fuels athletes to seek performance- enhancing substances, such as anabolic-androgenic steroids (AASs), togain an advantage over their opponents. Nonathletes espouse this same at-titude to ‘‘win’’ the battle of attractiveness. They view AASs as the means toachieving what they believe is a more desirable muscular physique. Thesebeliefs have filtered from professional, Olympic, and collegiate levels intohigh schools, middle schools, and grade schools. An enhanced understand-ing of AASs and the motivations behind their abuse will arm the pediatri-cian with the ability to engage one’s patients in a balanced discussion ofthe benefits and costly risks of AASs and successfully deter further use.
High levels of AAS abuse have been attributed to professional football players, bodybuilders, weight lifters, and track and field throwers sincethe 1960s. The exceptional athletic performance of the East German femaleswimmers in the 1976 Montreal Olympics brought further public attentionto AAS athletic use. It was not until the 1980s, however, that the medicalcommunity admitted that these substances were effective . Since thattime, the pervasive use of AASs by professional athletes has garnered signif-icant media attention, culminating most recently in the ongoing investiga-tion of the use of illegal performance enhancing drugs by some ofbaseball’s top players. Juiced, a book by Jose Canseco, details his steroiduse and the widespread use of anabolic steroids in Major League Baseball.
* Corresponding author. Division of Sports Medicine, Akron Children’s Hospital, Sports Medicine Center, 388 South Main Street, Suite 207, Akron, OH 44311.
0031-3955/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved.
doi:10.1016/j.pcl.2007.04.010 The fame achieved by such professional athletes may be what makes tryingAASs so enticing to adolescents.
Several studies have contributed to an enlarging body of evidence regard- ing the anabolic ‘‘tissue-building’’ effects of AASs on their primary target,skeletal muscle. The actions of AASs on the musculoskeletal system havebeen shown to influence lean body mass, muscle size and strength, proteinmetabolism, bone metabolism, and collagen synthesis . Over a periodof 10 to 20 weeks, a supraphysiologic dose of testosterone administered tohealthy young men can increase lean body mass, as well as muscle sizeand strength with or without exercise . These significant increasesare dose dependent and only occur with doses of 300 mg per week andhigher . The most profound effects are noted when supraphysiologicdoses accompany a training program and are used in conjunction witha diet adequate in protein and calories .
Testosterone-induced muscle hypertrophy and increases in muscle strength are the result of increases in the cross-sectional area of muscle fibers and my-onuclear number Research suggests that these anabolic effects are medi-ated by testosterone-influenced increases in muscle protein synthesis,creating a positive nitrogen balance . Androgen receptors in skeletalmuscle regulate the transcription of the target genes that control the accumu-lation of DNA needed for muscle growth. Complementary effects includeglucocorticoid antagonism, which minimizes the catabolic actions of cortico-steroids released during the stress of athletic activity. Similarly, stimulation ofthe growth hormone insulin-like growth factor-1 axis and enhanced col-lagen synthesis and bone mineral density are additional anabolic effects.
AASs induce a state of euphoria and diminished fatigue that enables pro- longation of training sessions by users. Recent data may explain how AASsexert these psychoactive effects on the brain. Henderson and colleagues proposed that AAS-mediated acute and chronic changes in the gamma-aminobutyric acid (GABA) receptor system cause many of the known behav-ioral effects. For instance, the immediate effects of decreased anxiety andenhanced sense of well-being that are experienced by AAS users likely arisefrom enhancement of forebrain GABAergic circuits. In contrast, anxietyand aggression are the result of a down-regulation of GABA receptor expres-sion secondary to chronic AAS exposure. Further study may reveal thatexpression of these behaviors is influenced by the age and gender of theAAS user and the particular chemical composition of the AAS administered.
The anabolic properties of AASs have proven beneficial for some thera- peutic applications. They have been used in clinical practice since the 1940s for the treatment of trauma, burns, extensive surgery, radiation therapy, andchronic debilitating illnesses . Before the advent of bone marrowtransplantation and synthetic erythropoietin, AASs were used often in thetreatment of various types of anemias. AASs have shown promise in treatingshort stature, as in Turner’s syndrome, or constitutional growth and pubertydelay. Since 1985, the clinical use of AASs has increased 400%, mostly dueto the management of AIDS-associated wasting syndrome. AASs may en-hance the effects of the increased caloric intake and exercise regimen A pilot study in malnourished HIV-infected children as young as 4 yearsold showed that oxandrolone treatment was well-tolerated and improvednutritional status. After 3 months of treatment, the study subjects experi-enced an accelerated rate of weight gain, increased body mass index, in-creased muscle mass, and decreased fat stores as compared withpretreatment values. The results were supported further by the improvedserum albumin levels noted during the course of treatment. Future studiesusing a larger study population and longer- or higher-dose AAS administra-tion would strengthen the current data . In patients with severe burns,AASs may play an important role in reversing the catabolic state. A smallprospective randomized study of patients who had burns showed that thosereceiving oxandrolone in addition to a high-protein diet experienced a signif-icantly greater increase in weight and physical therapy index than didpatients who were treated with diet alone . AAS therapy seems to bepromising in the treatment of malnutrition and muscle wasting seen inpatients who have end-stage renal disease. In addition to the increase inlean body mass, these patients also benefit from a stimulated erythropoiesisresulting from the administration of AASs . Such positive effectswarrant further study The nonmedical use of AASs has been banned by the International Olympic Committee, the United States Olympic Committee, and the Na-tional Collegiate Athletic Association. Such use also is denounced by theAmerican Medical Association, the American College Health Association,the American Academy of Pediatrics, the American College of Sports Med-icine, and the National Strength and Conditioning Association . Steroidsare banned from use by all major sporting leagues, although each has itsown testing and penalization policies . The US Federal Governmentand most state governments have enacted laws regarding the distribution,possession, or prescription of AASs. The Federal Food, Drug, and Cos-metic Act was amended as part of the 1988 Anti-Drug Abuse act, suchthat distribution of AASs or possession with intent to distribute withouta valid prescription became a felony. Such offenses are punishable bya prison term of up to 5 years or fines totaling $250,000 . In 1990, the Anabolic Steroids Control Act was signed into law, thereby classifyingAASs as Schedule III drugs within the Controlled Substances Act. TheDrug Enforcement Agency now controls the manufacture, importation, ex-portation, distribution, and dispensing of AASs Despite the above-mentioned barriers, AASs are still making their way into the hands of adolescents and children. Most commonly, the sourcesare bodybuilding gyms that obtain the drugs by way of a multimillion dollarillicit black market: foreign mail order, Internet dealers, or Internet pharma-cies . Most concerning about such sources is that the purity and actualcontent of the product received cannot be guaranteed.
Prevalence of adolescent anabolic-androgenic steroid use The first reported adolescent use of AASs was in 1959 by a high school football player . Current estimates of high school steroid usage rangefrom 4% to 11% in boys and up to 3.3% in girls The landmark studyof prevalence that was performed by Buckley and colleagues involveda nationwide survey of more than 3000 boys. They found that 6.6% ofmale high school seniors had tried steroids, with 67% initiating use by 16years of age and 40% using multiple cycles. These results have been confirmedin later studies of Indiana high school football players documenting a 6% userate and a 2003 Centers for Disease Control and Prevention report findinga 6.4% use of steroids by 12th-grade boys. The largest nationwide cohort ofnearly 50,000 students is being examined in the Monitoring the Future study. As of 2004, results of this ongoing study indicated a 1.3%, 2.3%, and3.3% annual prevalence of male AAS users in the eighth, 10th, and 12thgrades, respectively. Girls in the 12th grade had a 1.7% use rate in this study,whereas the Centers for Disease Control and Prevention reported a 3.3% life-time prevalence in 12th-grade girls.
Prevalence studies have extended to middle school populations as well. A 1993 study of Modesto, California seventh-grade students was the first todocument the use of steroids in students aged 12 to 15 years The overallrate of use reported was 3.8%, with more male students (4.7% versus 3.2%in female students) admitting to using AASs. A later article published datafrom a study of Massachusetts students between 9 and 13 years of age .
AAS use was reported by 2.7% of all middle school students surveyed, with2.6% of boys and 2.8% of girls reporting use. As in other studies, the prev-alence of AAS use increased with increasing age. Both of these regionalstudies were consistent with data from Yesalis , who reviewed AAS prev-alence rates among junior high school students in the United States (2% forsixth graders and 2.3 to 3% for eighth graders).
AAS use by adolescents is not limited to the United States. Three Cana- dian studies, two Swedish surveys, two South African investigations, oneBritish study, and one Australian investigation reported an overall preva-lence range between 1% and 3%. Although slightly lower, these ratesapproximate those reported in the United States, demonstrating that theimpact of AASs on athletic performance and physical appearance reachesacross cultures Risk factors for adolescent anabolic-androgenic steroid abuse Many studies of adolescent AAS users and abusers have attempted to create a profile of the typical user. The following discussion reviews someof the data relating to demographics, school performance, athletic participa-tion, and personality of AAS users.
Generally, the relative risk of AAS use is at least two to three times greater for male adolescents. The review of numerous studies showsa wide variation in the age range of AAS users. Race and ethnicity ofAAS users is equally unclear. Some studies reported greater use amongminorities whereas others revealed a higher rate among whiteadolescents One regional study reported a significantly higher ratein blacks Other studies reported no racial difference in adolescentAAS use. Likewise, no clear-cut relationship exists regarding geographiclocation, city size, or school size.
There may be some association between AAS use and poor academic performance. In a large national study, DuRant and colleagues statedthat students who reported below-average academic performance had a sig-nificantly higher prevalence of AAS use than did average or above-averagestudents; however, two studies, reported no relationship between academicachievement and AAS use Future studies regarding this question areneeded.
Adolescents use AASs as a method to improve their athletic performance.
AAS users are significantly more likely than are nonusers to participate inschool-sponsored athletic programs . Sports requiring muscu-lar strength and power are those most closely associated with AAS useamong their participants. Such sports include football, wrestling, and trackand field . Faigenbaum and colleagues reported greater AAS use in gymnastics and weight training in their study sample.
Strength undoubtedly is an asset to gymnasts, and, thus, correlates wellwith the observed higher percentage; however, they were concerned withthe suggestion that some young gymnasts may use AASs to stunt theirgrowth because they believe that small stature confers an advantage in gym-nastics. It is important to realize that approximately 30% to 40% of adoles-cent AAS users do not participate in a school-sponsored sport. These userslikely participate in bodybuilding or weightlifting activities .
A considerable percentage of adolescents turn to AAS use to help them achieve an attractive physique. This is the second most popular reason forusing AASs. One study of bodybuilders suggests that the drive for a muscu-lar physique sometimes reaches an unhealthy extreme and likens the use ofAAS to the ‘‘unhealthy extremes’’ that are characteristic of anorexic andbulimic individuals. Just as eating disordered women see their bodies aslarger than they actually are, some men perceive themselves as smallerthan they actually are. Taylor refers to this phenomenon as ‘‘bigamer-exia’’ and suggests that this misperception may be a contributory factor inAAS use. This misperception is likely evident in many ninth-grade boys,whodin the early stages of pubertydare impatient with their muscular de-velopment. Perceiving themselves smaller than their peers, these boys mayengage in AAS use as a shortcut to increasing muscle strength and size. Exposure to the media may intensify this body dysmorphia. Fieldand colleagues examined this possibility in a study of supplement useamong adolescents. They found that girls and boys who reported thinkingfrequently about wanting more defined muscles and those who were tryingto emulate the look of same-gender figures in the media were more thanthree times more likely to use agents to build muscle or improve appearance.
Adolescent AAS use has been associated with the use of other harmful drugs, including cigarettes, smokeless tobacco, marijuana, alcohol, cocaine,and injected drugs. These behaviors support a risk behavior framework hy-pothesized by Jessor in his Problem Behavior Theory. He proposed thatthere are intraindividual similarities among adolescent problem behaviorssuch that they cluster to form a ‘‘risk behavior syndrome.’’ Thus, AASuse would be considered a part of this cluster rather than an isolated behav-ior. Middleman and colleagues applied this theory to a study of Massa-chusetts high school AAS users. They noted that the frequency of AAS usewas associated with driving after drinking alcohol, carrying a gun, sexualpromiscuity, unprotected intercourse, injury in a fight requiring medical at-tention, history of a sexually transmitted disease, not wearing a helmet ona motorcycle, not wearing a passenger seatbelt, and a suicide attempt requir-ing medical attention. Another concerning health-compromising behavior isthe sharing of needles and multidose vials by between 25% and 33% of adolescent AAS users. This practice contributes to the risk for acquiringinfections, such as HIV, hepatitis B, and hepatitis C .
Anabolic steroids may be taken orally or injected intramuscularly and are grouped into three main classes Testosterone esters, such astestosterone propionate, are injected compounds and constitute class I. ClassII agents include the nortestosterone derivatives (eg, nandrolone decanoateand nandrolone phenpropionate). Class I and II AASs exert effects at andro-gen receptors as well as at estrogen receptors by way of aromatization to estra-diol . The third class of AASs are those alkylated at C-17 and are the orallyadministered compounds oxymetholone, methandrostenolone, and stanozo-lol. Alkylation of these compounds involves the addition of a methyl or ethylgroup to the carbon at position 17 of the steroid backbone. The alkylationslows the hepatic metabolism of these agents . These and other commonoral and injectable preparations are listed in A typical pattern of use consists of a combination of injectable and oral ste- roids taken during 6- to 12-week cycles. Injectable forms tend to be favored byusers because they are less hepatotoxic than the oral forms Because oral Table 1More commonly abused anabolic steroids phenyl propionate,isocaporate, decanoate (I) Abbreviations: O, oral; I, injectable.
a Abused dosages may vary greatly by gender, personal experience, availability of specific steroids, performance and appearance goals, and the simultaneous use of several steroids.
Data from Bahrke MS, Yesalis CE, Brower KJ. Anabolic-androgenic steroid abuse and per- formance-enhancing drugs among adolescents. Child Adolesc Psychiatr Clin N Am1998;7(4):826.
preparations are cleared from the system more quickly, they are the preferredform of steroids when drug testing is anticipated. The simultaneous use of mul-tiple steroids is referred to as ‘‘stacking.’’ A pattern of increasing a dosethrough a cycle is called ‘‘pyramiding.’’ Pyramiding can lead to doses 10 to40 times greater than the dose recommended for medical indications. By stack-ing and pyramiding doses, the user hopes to maximize steroid receptor bind-ing, thereby reducing toxic side effects. These patterns have remained popular,despite the lack of scientific evidence of a benefit Some users take otherdrugs concurrently in an effort to minimize side effects. These ‘‘accessory’’medications include clomiphene and human chorionic gonadotropin andare administered to reverse the endogenous testosterone production. Addi-tionally, tamoxifen and antiaromatase drugs can prevent or decrease gyneco-mastia by limiting estrogenic effects and the metabolism of excess testosteronederivatives to estradiol It is not uncommon for users to take other legalperformance-enhancing substances and dietary supplements, such as creatine,glutamine, and protein, while using AASs .
For years, scientists have attempted to dissociate the anabolic properties from the androgenic characteristics of AASs, to no avail. Therefore, bothcomponents exert adverse effects on various tissues and body systems.
Various studies have shown transient elevations in liver function tests in conjunction with AAS use The C-17 alkylated oral preparationsare associated most often with liver toxicity Elevations in aspartate trans-aminase, alanine transaminase, lactate dehydrogenase, and alkaline phospha-tase have been reported Values measured can be two to three times thenormal range, peaking within 2 to 3 weeks of consumption. Usually, a returnto baseline is seen within several weeks of discontinuation . Many AASusers also abuse alcohol, thus compounding the hepatic adverse effects.
Anabolic-related cholestasis has been reported to occur in varying frequency from a few cases to up to 17.3% in some studies . The tran-sient jaundice that results is secondary to biliary stasis rather than structuralhepatic injury. Structural lesions have been studied in case reports of theblood-filled cysts of peliosis hepatis Internal hemorrhage or hepaticfailure can occur secondary to such lesions.
Hepatocellular adenomas have been associated with high-dose AAS, long periods of administration of AAS, or in AAS users with a predisposing med-ical condition . It is particularly difficult to differentiate adenomasfrom hepatocellular carcinoma by ultrasound. Prompt identification of theselesions is critical because the potential for malignant transformation mayincrease if a late diagnosis is made Altered lipid profiles in AAS users are reflected in increased low-density lipoprotein and decreased high-density lipoprotein The oral C-17alkylated steroids seem to exert the greatest effects on the lipid profileThrombus formation has been postulated by way of these ad-verse lipid changes and is supported further by findings of AAS-induced in-creased platelet aggregation, enhanced coagulation enzyme activity, andcoronary vasospasm .
Hypertension in AAS users has been reported and is likely the result of blood volume increases and fluid retention This effect, as well asthe finding of increased septal thickness and left ventricular mass reportedin AAS users can lead to significant detrimental cardiac remodeling.
Exogenous steroid administration provides feedback inhibition of lutei- nizing and follicle-stimulating hormones, which leads to testicular atrophyand decreased spermatogenesis. This testicular impairment is reversedupon cessation of AAS use. Excess steroids undergo peripheral aromatiza-tion to estrogens, which results in feminizing changes of high voice pitchand male gynecomastia . In long-term AAS abuse, this gynecomastiais irreversible, leaving surgical correction as the only solution . In addi-tion to the female side effects of decreased menstruation and breast tissueatrophy, virilizing effects also occur and include deepened voice, clitorome-galy, and hirsutism. Sometimes these effects are irreversible, even after dis-continuation of AAS use Experimental evidence exists that the use of AASs combined with intense exercise can cause structural and biomechanical alterations of tendons re-sulting in rupture. Structurally, the collagen fibril alignment is highly disor-ganized. From a biomechanical perspective, when muscle strength isincreased with AAS use, the tendon becomes stiffer, absorbs less energy,and is more likely to fail during physical activity Premature growth cessation due to physeal closure in younger users has not been studied systematically. Such case reports of the resultant perma-nent short stature have been described for several decades .
Severe cases of acne, especially on the face and back of AAS users, are common dermatologic findings. Premature baldness is noted as well. Dick-inson and colleagues reported multiple cases of serious muscular ab-scesses resulting from the common practice of shared needles and shared steroid vials among adolescent AAS users. A limited knowledge of sterile in-jection technique, as well as limited access to sterile needles and syringes arelikely additional causative factors in these infections.
AAS use has been associated with self-reported changes in mood and be- havior. A study by Pope and Katz identified psychiatric syndromes inweightlifters using AASs. Twenty-three percent of AAS users experiencedmajor mood changes of mania, hypomania, or major depression. Also com-mon in AAS users was aggressive behavior resulting in fights, domestic dis-turbances, assaults, and arrests. Data from the National Household Surveyon Drug Abuse have demonstrated a strong association between AAS useand self-acknowledged acts of violence against people and crimes againstproperty . In general, the behavioral effects of AASs are variable,short-lived on discontinuation, and seem to be related to the type and dos-age of AAS.
The potential for physical dependence upon AASs does exist. In one study of AAS users, 50% of them met the Diagnostic and Statistical Manual of Men-tal Disorders, Fourth Edition criteria for dependence or abuse of steroids .
Physical symptoms of withdrawal are similar to those seen during alcohol andopioid withdrawal, including diaphoresis, myalgias, nausea, and increases inblood pressure and heart rate . Withdrawal may also be characterizedby depressive symptoms . Deeply entrenched body dissatisfaction andbody dysmorphic disorder may underlie a psychologic dependence. Clearly,the addictive potential of AASs cannot be discounted The implementation of drug-testing policies has been considered as a pos- sible preventive strategy. Data from the National Federation of State HighSchool Associations indicate, however, that only 13% of schools test ath-letes and, of those schools, only 29% test for AASs. The reasons for thelow number of testing programs include financial constraints (w$120 pertest) and the fact that testing often can be circumvented by the user. Dosetitration with newer transdermal delivery systems of testosterone or discon-tinuation of use before a scheduled test can maintain levels below a testingthreshold . Testing only athletes also will miss a significant percentage ofnonathlete users.
Educational programs have been suggested as a more effective means of deterring AAS use. Goldberg and colleagues tested a team-based educa-tional intervention designed to reduce Portland, Oregon high school footballplayers’ intent to use AASs. The Adolescents Training and Learning toAvoid Steroids Program consisted of 50-minute class sessions that were de-livered over a 7-week period by coaches and athlete team leaders. The sessions combined drug education with attainment of personal skills to as-sist athletes in resisting the social influences that fuel an athlete’s desire touse AASs. Athletes in this intervention group gained a greater knowledgeof the consequences of AAS use, were more skeptical about the media’s pro-motion of AASs, and had improved drug-refusal skills. These results are cer-tainly encouraging and follow-up data are eagerly anticipated.
The pediatrician’s office can be a valuable educational setting as well. Us- ing ‘‘scare tactics’’ as a prevention effort to dissuade adolescents from be-coming AAS users has been proven to weaken physician credibility andmay even encourage use Rather, Metzl offers the concept of‘‘thoughtful discouragement’’ as the key to effective prevention. He recom-mends that the clinician first recognize that a patient may be using AASs.
The sports preparticipation physical examination offers an ideal opportu-nity to note any physical changes suggestive of AAS use and to ask whetherthe patient is using a performance-enhancing substance. Education is thenext step and should be a balanced discussion focusing on the current re-search, the physiologic effects, and the adverse events. A concerning trendin 12th graders showed a steadily decreasing perceived risk for steroid useyearly since 1993. Only 55% of seniors now consider steroid use as a greatrisk . Finally, healthy alternatives to AAS use must be presented. A su-pervised strength-training program among children as young as 8 years ofage is a safe and effective means of increasing strength and improving ath-letic performance . By emphasizing repetitions rather than maximumweight lifting, baseline strength can be increased by 30% to 40% Our society equates success with winning. The drive to win athletic com- petitions or the obsession with achieving the perfect physique has made ad-olescents and children increasingly vulnerable to the lure of AASs. Theincreases in muscular size and strength that are characteristic of AASs occurwith attendant short-term adverse effects and the potential for long-termhealth consequences. A mindset of invincibility that is typical of many ado-lescents allows them to be willing to pay the price of these negative eventsfor the chance to gain a competitive edge.
Educational programs addressing the social, media, and peer influences that perpetuate adolescent use of AASs have shown promise in decreasingthe intent to use. Such educational programs need to be directed towardmiddle school classrooms to decrease the rate of first use in this age group.
Physician dissemination of accurate information to parents, coaches, andschool administrators is vital to the creation of intervention programs. Bydemonstrating a knowledge base that earns adolescent respect, the pediatri-cian will be able to effectively discourage AAS use and convince the patientthat there is no substitute for sound nutrition and a sensible strength-train-ing program.
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MPMI Vol. 13, No. 12, 2000, pp. 1356–1365. Publication no. M-2000-1002-01R. © 2000 The American Phytopathological Society Restriction Enzyme-Mediated Integration Used to Produce Pathogenicity Mutants of Colletotrichum graminicola M. R. Thon, E. M. Nuckles, and L. J. Vaillancourt Department of Plant Pathology, S-305 Agricultural Sciences Center-North, University of Kentucky, Lexington We

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SELECTION OF SUSCEPTIBILITY TEST BROTH Use Sensititre CAMHBT for rapid growing mycobacteria, Nocardia and other aerobic Actinomycetes or Mueller Hinton broth with OADC for slow growing mycobacteria. Sensititre broths are performance tested for use with SENSITITRE® Broth Microdilution (MIC) Method: INOCULATION AND INCUBATION For Rapidly Growing Mycobacteria (RGM), Slowly

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