Adverse Effects
The adverse drug effects of AS can be divided into 5 general categories: hepatic, cardiovascular, reproductive/endocrine, dermatological and psychiatric (table II).
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[Email Jumpstart To Image] Table II. Most common adverse effects of anabolic steroids
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Hepatic Effects
The association between liver function tests (LFT) elevations and AS has been documented in the literature.[20,28,33] Bodybuilders are well versed and quite concerned about this adverse drug effect. Elevations in aspartate transaminase, alanine transaminase, lactate dehydrogenase and alkaline phosphatase have been reported with AS use.[20] Although weightlifting alone can elevate LFT, individuals using AS are at a greater risk of having elevated LFT.[20] However, hepatic enzymes usually return to normal once AS are discontinued. The reversible course of the LFT elevations explains why athletes administer AS in a cyclic pattern.[34] Consequently, if AS are administered continually for at least 1 month, but generally for greater than 2 to 5 months at supraphysiological doses, dose-dependent jaundice and hepatic dysfunction are likely to develop.[34] Death caused by AS hepatotoxicity is extremely rare.[34]
Of the AS, the C-17 alkylated AS are more often associated with liver toxicity.[34] The most common C-17 alkylated AS used by athletes are the oral agents such as methyltestosterone, metandienone, oxymetholone, oxandrolone and stanozolol. Nonalkylated intramuscular agents such as testosterone and nortestosterone are much less likely to produce liver problems.[20,34] However, many AS users misuse other substances including alcohol, which could possibly compound hepatic adverse drug effects. There have been cases of carcinoma of the liver associated with either high dose AS, long periods of administration of AS or in AS users with predisposing medical conditions.[20,34] Cyclic administration of AS reverses the risk of liver toxicity.[3] Additionally, avoiding C-17 alkylated agents (oral agents) is another practice that decreases hepatotoxicity. The ultimate means of preventing liver toxicity are AS abstention and the avoidance of other potentially hepatotoxic agents, such as alcohol. Although accepting of these facts, athletes are not usually concerned since the benefits of increased muscle mass and strength overshadow the known risks.
Cardiovascular Effects
Use of AS can lead to detrimental changes in serum lipid profiles. Potential changes include increases in low-density lipoprotein (LDL) and decreases in high-density lipoprotein (HDL).[27,33,35] Bodybuilders are generally of the opinion that since steroids are chemically similar to cholesterol, they will affect lipids in the same way as eating too much cholesterol. For bodybuilders this effect is not harmful since many of them are on ketogenic diets, which emphasises moderate to high fat, and low to moderate complex carbohydrate foods, while consuming extremely high amounts of protein.[32] Lipid changes are typically unpredictable and are unrelated to dosage and agents administered. A meta-analysis [35] conducted in 1991 reported decreases in HDL of 39 to 70% (mean 52%). These changes generally occur within the first week of administration and normalise within 3 to 5 weeks after AS discontinuation. Conversely, reports of LDL elevations between 11 to 100% have been reported (mean 36%).[35] Since HDL levels decrease and LDL levels increase, total cholesterol levels generally do not reflect these changes and the atherogenic potential of AS can often be overlooked.[35]
Unfortunately, many bodybuilders seem to believe that cholesterol monitoring is all that it required to monitor their lipid status. Triglyceride levels are also decreased by the exogenous androgen administration.[3] The long-term impact on morbidity and mortality of labile lipid profiles is unknown. However, an increase in LDL levels might directly contribute to arteriosclerosis especially if these agents are used over long periods of time.[8] With an increased risk of cholesterol plaques in the coronary vessels, a subsequent thrombus may occur in athletes using AS.[8] AS also stimulate platelet aggregation, increase coagulation enzyme activity, and cause coronary artery vasospasm.[8] Thus, AS have the potential to predispose users to thrombus formation by reductions of HDL, increases in LDL, increased platelet aggregation, coronary artery vasospasm and enhanced coagulation enzyme activity.
Elevations in blood pressure in AS users have been reported and most likely result from blood volume increases and fluid retention.[8,27] This effect has not been well studied in humans, although is well-documented in animal studies.[8,27] Anecdotally, bodybuilders will complain of feeling an increase of pressure in their head and body resulting from what they believe is elevated blood pressure. AS also increase heart rate, which may lead to hypertrophy of the left ventricle.[8,36] Case studies of AS users at autopsies have found cardiac hypertrophy in these patients.[8] The consequences of cardiac hypertrophy can lead to decreased maximal oxygen uptake, remodelling of the heart, myocardial ischaemia and cardiomyopathy.[8] These effects are serious and can lead to sudden cardiac arrest, and will persist well after cessation of AS.[8] Unfortunately, it is difficult to ascertain whether the effects of AS on the heart are independent of the other agents present in the polypharmacy regimens of many AS users such as amphetamines as weight loss agents, as well as alcohol and tobacco cigarettes.
Reproductive/Endocrine Effects
In men, AS administration produces a predictable, dose-dependent depression of luteinising hormone (LH), and follicle-stimulating hormone (FSH) via the negative feedback loop of the hypothalamic-pituitary-gonadal (HPG) axis.[30,37,38] As both LH and FSH are required for spermatogenesis, AS administration can lead to hypogonadotropic hypogonadism. The resulting effects of these physiologic changes include declines in sperm density and sperm count, decreased sperm motility, abnormal sperm morphology, testicular atrophy, and no change in libido.[10,27,39,40] However, the observed effect on libido was based on testosterone doses not exceeding 500 mg/wk. These effects generally worsen with increased use of AS, and severe oligospermia can lead to infertility.[41] Bodybuilders are usually aware of these effects and often use agents such as chorionic gonadotropin (hCG) to stimulate LH production and testicular testosterone production.[32] Turek et al.[41] described a case report of an AS user who was administered hCG 2000 to 3000 units three times a week. Following 3 months of treatment, the patient's wife became pregnant, reportedly due to LH and sperm normalisation. FSH activity is required for completion of spermatogenesis. However, FSH activity is not precipitated by hCG. This leads to the belief that sperm counts are increased by hCG, but they may not be 100% viable. Many athletes who discontinue AS have their sperm morphology normalise within 4 months. However, this is not necessarily always the case since normalisation is a function of both the magnitude and duration of AS exposure.[38] Some individuals required up to 1 year for normalisation of morphology and motility.[37,38]
AS can also lead to feminisation in males from the conversion of testosterone to estrogen metabolites (aromatisation).[27] As a result, many AS users report increased voice pitch and gynaecomastia, although these effects are unpredictable. Our experience notes that many users of AS self-administer the antiestrogenic agent tamoxifen to antagonise these effects. Unsurprisingly, the efficacy and safety of this practice remains to be confirmed. Our experiences with AS-using bodybuilders indicate that hair loss is minimal with testosterone ester doses of less than 600mg/wk. The adverse effect is reversible on discontinuation of the AS.
AS use in women can lead to hirsutism, acne, deepening of the voice, clitoral hypertrophy, decreased breast mass, decreased menstruation or amenorrhoea, increased appetite and male pattern baldness. Even after discontinuation of the causative agents, these effects are sometimes irreversible.[42] The willingness to tolerate any physical and/or reproductive adverse drug effect to achieve an athletic goal is unique among AS administrating athletes.
Other endocrine effects include decreased thyroid function and decreased serum T-4 binding globulin concentrations.[3] AS is known to cause acne and other skin changes including, but not limited to, oily hair and skin, alopecia, sebaceous cysts and hypertrophy of sebacious glands. High doses of AS increase the amounts of Propionibacteria acnes, free fatty acids and cholesterol in the skin, which lead to these dermatological changes.[3]
Psychiatric Effects
Aggressive behaviour and mood changes have been linked to use of AS in case reports, animal studies and controlled clinical trials.[43,44] Although these reports describe increases in aggression and violent behaviour with AS use, there are relatively few controlled studies relating aggressive behaviour and mood changes to AS use among a bodybuilding and/or weightlifting population. Despite the nature of various reports on mood changes with AS administration, many bodybuilders report that they feel AS elicit an antidepressant-like feeling. This observation was recently challenged when Seidman et al.[45] reported no antidepressant effects of testosterone replacement in men with major depressive disorder. Conclusions of this study are limited and future studies of AS use in depression are needed.
Six randomised controlled studies have administered supraphysiologic doses of testosterone to healthy male participants and observed them for changes in their mental status.[40,46-50] In general, these studies indicate little risk of mood changes or aggressive behaviour with doses of up to 300 mg/week. However, with larger doses, changes in various mood and aggression subscales have been observed.
Pope et al.[48] described significant increases in the Point Subtraction Aggression Paradigm (PSAP), and the Young Mania Rating Scale (YMRS) among recipients of higher testosterone doses (600 mg/wk) compared with placebo.[48] While between-group differences were observed, the distribution of individual scores was also important. On average, the endpoint YMRS scores were 3 points higher in recipients of testosterone. However, this difference does not indicate that all participants had a 3-point increase, but rather that most participants experienced no change, while a few individuals experienced marked changes. While Pope et al.[48] was able to demonstrate significant alterations in aggression and mood endpoints, the majority of controlled studies have not. This may be because psychiatric adverse drug effects are dose-dependent and all of the negative studies did not expose the participants to large enough doses to induce a change in the participants' mental status. Additionally, the negative studies indicate that individuals with a positive psychiatric history including personality disorder may be more susceptible to changes in mood and aggression.[40,46,47,49,50]
Although AS use promotes aggression and mood changes, there are several limitations to the data. First, many of the studies did not enrol bodybuilders and/or weightlifters as participants.[40,46,47,49,50] The inclusion of healthy male participants does not represent individuals who are likely to use AS such as weightlifters, bodybuilders and other athletes. The second limitation is the exclusion of individuals with psychiatric disorders, particularly personality disorders. Such individuals may be more susceptible to AS-induced psychiatric changes than normal control participants. Finally, AS regimens were limited to a single agent administered weekly at doses less than 600 mg/week.[40,46-50] These regimens do not represent the multidrug combinations (stacks) and/or mega-doses of AS used by bodybuilders. Furthermore, the maximum dose given in clinical trials was 600 mg/week for 2 weeks, which is far below the doses commonly used by bodybuilders.[46,48]
Data regarding AS use in bodybuilders and/or weightlifters and associated psychiatric changes are limited. Yates et al.[6] compared weightlifters that were either AS users (n = 20) or non-AS users (n = 20) to alcoholics (n = 20) and non-weightlifting community controls (n = 20). Personality disorders were assessed using the Diagnostic and Statistical Manual of Mental Disorders (3rd edition, revised) [DSM-III-R] criteria for cluster A, B and C personality traits, and the self-report personality diagnostic questionnaire. Forty-five percent of AS users demonstrated antisocial personality traits compared with 0% of community controls (p < 0.001).[6] In a later study, Yates et al.[51] examined the Buss-Durkee Hostility Inventory (BDHI) scores for eight AS users, four previous AS users to 25 non-AS using weightlifters. There were no significant differences among AS users, non-AS users and previous users on overall BDHI scores, but there were significant elevations on the BDHI subscores of assault, indirect aggression and verbal aggression among AS users.[51]
A more recent study by Pope and Katz [52] conducted interviews with weightlifters using AS (n = 88) and non-users (n = 68). DSM-III-R criteria were applied to identify psychiatric syndromes. Twenty-three percent of AS users experienced major mood changes of mania, hypomania or major depression. In contrast, the rate of major mood changes was only 6% among non-AS users (p < 0.07). Aggressive behaviour, including fights, domestic disrupts, assaults and arrests, was common among AS users. All participants denied previous behaviour of this type before AS use.[52]
Our experiences with AS users indicate that psychiatric effects are unique to each individual and overall conclusions are difficult to make. However, there are data suggesting that AS administration may be addictive. In interviews with 49 AS users, at least one DSM-III-R symptom of dependence was reported by 94% of the sample, while three or more symptoms were reported by 57% of the sample.[53] Three symptoms are required for a diagnosis of drug dependence. A recent article [54] reported that 23% of AS using participants met DSM-IV criteria dependence, while 25% met DSM-IV criteria for abuse. The authors concluded that AS were addictive and suggested that dissatisfaction with body size might lead to dependent patterns of use.[33] Our experience with many athletes using AS suggests that dissatisfaction with their body size and increases in strength and size obtained from AS are the primary stimuli for continued usage of these agents. Although these observations may be related to an underlying body dysmorphic disorder diagnosis, and unrelated to AS usage, no studies have been conducted addressing this issue in this population. Clinicians should not discount the addictive potential of these agents, as competitive athletes are often willing to use any substance to obtain their goals.
