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Harry Rashid is an innovative general practice registrar with an honorary contract with Birmingham Heartlands and Solihull NHS Trust, having initially worked in general adult psychiatry for the Birmingham and Solihull Mental Health NHS Trust. He has a specialist interest in sports medicine and anabolic steroid misuse. Sara Ormerod is a specialist registrar in old age psychiatry currently working for Birmingham and Solihull Mental Health NHS Trust. Her clinical and research interests include the interface between physical and psychiatric disorders. Ed Day is a senior lecturer in addiction psychiatry at the University of Birmingham (Department of Psychiatry, Queen Elizabeth Psychiatric Hospital, Mindelsohn Way, Edgbaston, Birmingham B15 2QZ UK. Email: e.j.day{at}bham.ac.uk), and an honorary consultant psychiatrist with the Birmingham and Solihull Mental Health NHS Trust. His research interests include developing innovative pharmacological and psychological treatments for alcohol and drug dependence.
| Abstract |
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Anabolic androgenic steroids (which for conciseness we will call anabolic steroids hereafter) are prescribed for the treatment of male hypogonadism, and there is evidence for their efficacy in the treatment of cachexia associated with HIV, cancer, burns, renal and hepatic failure, and anaemia associated with leukaemia and hepatic failure (Basaria et al, 2001). To the general public anabolic steroids are more commonly known as drugs used by competing athletes as a performance-enhancing (ergogenic) aid. However, the misuse and harmful use of anabolic steroids is no longer the sole domain of elite professional athletes. In recent years the recreational use of these drugs has increased significantly, usually for the cosmetic purpose of enhancing appearance (Johnston et al, 2003). Misuse is also no longer limited to a predominately male population, as females are becoming increasingly involved in using anabolic steroids.
Unless otherwise stated, reference in this article to steroid use in general indicates the taking of steroids without prescription. In particular, misuse indicates that the drug is being taken in a way that would not comply with medical recommendations and harmful use indicates a pattern of use that is causing damage to health but does not meet ICD10 criteria for dependence (Box 1
).
| Box 1 ICD10 criteria for dependence ICD10 criteria include experience of at least three of the following during the past year:
(World Health Organization, 1992)
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| Anabolic steroids and the law |
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Box 2 Controlled drugs in the UK
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In the USA, the Anabolic Steroid Control Act of 2004 was introduced in response to the growing use of steroid precursors (pro-steroids) by professional athletes in particular, thus expanding the list of substances available on prescription only.
| How common is steroid misuse? |
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Over the past decade the harmful use of anabolic steroids has increased both in the UK and in the USA. This was highlighted in a report by the British Medical Association in 2002, which classified steroid misuse as a public health risk. The report (British Medical Association Board of Science and Education, 2002) found that as many as half of the members of dedicated bodybuilding gyms admitted to taking anabolicagents, and that steroid use ran as high as 13% even in some high-street fitness centres. A third of all general practitioners were treating patients who took steroids, and needle-exchange programmes for heroin addicts were reporting increasing numbers of steroid users among their clients.
An annual survey of adolescent drug use in the USA in 2002 found a sharp increase in the lifetime use of anabolic steroids, with lifetime prevalence increased by 1.7% in 10th graders (1516 years old) and 2.9% in 12th graders (1718 years old) over a 10-year period (Johnston et al, 2003). Recent data from the UK suggest a large rise in anabolic steroid misuse over the past year by a group of people who are distinct from users of other illicit drugs (Druglink News, 2006).
| Who misuses steroids? |
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Recreational users of anabolic steroids are the most rapidly expanding group, and their aim is to enhance their physical appearance in order to receive the admiration that Western societies give to a perfectly toned body. A much smaller proportion of those who misuse steroids have experienced physical or sexual abuse, and are trying to increase their muscle size to protect themselves. A further group (possibly between 5 and 10%) includes people who have a form of body dysmorphic disorder (sometimes called reverse anorexia nervosa), in which they believe that they look small and weak, even if they are large and muscular (Brower et al, 1991).
| How are anabolic steroids used? |
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Stacking is the use of more than one steroid at a time, to maximise increases in lean muscle mass, weight gain and strength. The drugs may be administered by different routes, for example as a combination of injectable and oral steroids.
In pyramiding the user follows a cycle of building up to a peak dose and then tapering back down towards the end of the cycle, in the hope of allowing the bodys hormonal system time to recuperate and maintain homoeostasis.
Some people use anabolic steroids continuously for years. Various additional drugs are taken to combat the side-effects of the steroids, and these include human chorionic gonadotrophin, diuretics, thyroid hormones, growth hormone and insulin (Table 2
).
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| Psychiatric complications |
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Aggression and violence
Empirical studies in both animals and humans have shownan increase in aggression in both males and females exposed to anabolic steroids (Eisenberg & Galloway, 2005), and self-reported aggression may be the only sign of steroid misuse (Copeland et al, 2000). Moderately high doses of testosterone cypionate have been shown to increase aggressive responding in individuals who have not used steroids before (Kouri et al, 1995), and increasing doses of methyltestosterone have been correlated with increasing irritability, mood swings, violent feelings and hostility (Su et al, 1993). Misusers of anabolic steroids subjectively report significantly more fights, verbal aggression and violence towards their significant others during periods of use compared with periods of non-use (Choi & Pope, 1994). There have been several case reports of what users call roid rage, frenzied violent behaviour during the high-dose cycles of steroid use (Lukas, 2003). In 88 athletes who were using anabolic steroids Pope & Katz (1994) found that aggressive or violent behaviour often accompanied steroid-associated manic or hypomanic episodes. Participants admitted to a range of serious episodes, including property damage, assault, being involved in a murder plot and beating a pet dog. Several of the sample had been expelled from home by parents, wives or girlfriends because of their intolerably aggressive behaviour. Nearly all denied comparable behaviour before steroid use. Other work has suggested that adolescents who abuse anabolic steroids have nearly triple the incidence of violent behaviour (Dukarm et al, 1996).
Psychosis
In earlier research, Pope & Katz (1988) studied 41 individuals who used anabolic steroids. Of these, 5 (12.2%) had psychotic symptoms and 4 (10%) had sub-threshold psychotic symptoms while taking steroids: none had these symptoms when not taking them. A subsequent larger study (Pope & Katz, 1994) found similar results, with psychotic symptoms diagnosed in 3% of the 88 users on-cycle, but in none off-cycle. The risk of developing psychotic symptoms may be related to high-dose testosterone (Pope & Katz, 1994; Hall et al, 2005).
Clinical presentations include grandiose and paranoid delusional states that often occur in the context of a psychotic or manic episode. Symptoms usually resolve in a few weeks if steroid use is discontinued, although may persist for as long as a month even if adequately treated with antipsychotics (Hall et al, 2005).
Personality disorders
Self-report questionnaires and informant histories have been used to retrospectively assess the personality type of anabolic steroid misusers before their first use. Such work suggests that they start out with personalities similar to those of non-using bodybuilders, but develop abnormal personality traits that could be attributed to steroid misuse (Eisenberg & Galloway, 2005). Cooper et al(1996) identified a high rate of abnormal personality traits in a sample of 12 bodybuilders who had used anabolic steroids compared with a matched group who had not. The reported personality traits of the steroid users before the onset of use did not differ from those of the non-users, but in the user group there were significant differences between the before and after traits. During steroid use, individuals were more likely to score higher on paranoia, schizoid, antisocial, borderline, histrionic, narcissistic and passive aggressive personality profiles. Other studies have suggested that antisocial personality disorder is slightly more likely among anabolic steroid users than among non-users (Pope & Katz, 1994). Steroid users have been shown to have a higher prevalence of cluster B (histrionic, narcissistic, antisocial and borderline) personality traits than community controls (Yates et al, 1990).
Mood and anxiety disorders
Affective disorders have long been recognised as a complication of anabolic steroid use. Case reports describe both hypomania and mania, along with irritability, elation, recklessness, racing thoughts and feelings of power and invincibility that did not meet the criteria for mania/hypomania (Eisenberg & Galloway, 2005). Of 53 bodybuilders who used anabolic steroids, 27 (51%) reported unspecified mood disturbance (Lindstrom et al, 1990).
The above-mentioned study by Pope & Katz (1988) involving 41 steroid-using bodybuilders used structured interviews to measure affective symptoms according to DSMIIIR criteria. They identified 5 participants (12.2%) who met the criteria for a manic episode during steroid exposure; a further 8 (19.5%) only narrowly missed the diagnosis. Significantly more participants developed a full affective syndrome during periods of steroid exposure (22%) than non-exposure (5%), and 10 were stacking when they experienced manic symptoms.
In a later prospective study, Pope and colleagues (2000) gave placebo or 600 mg testosterone to males aged 2050 years with no history of steroid use or past psychiatric illness. In the testosterone group, 6% of the men becoming mildly hypomanic and 4% becoming markedly hypomanic.
Su et al(1993) administered methyltestosterone (40 or 240 mg/day) or placebo to 20-year-old healthy men, and one participant developed an acute manic episode.
There is also evidence that depression can be associated with withdrawing from steroids: in Pope & Katzs original (1988) study 12.2% of those using anabolic steroids developed DSMIIIR major depression when they stopped taking the drugs.
| Medical complications |
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| Box 3 Physical signs of anabolic steroid use Musculoskeletal system
Cardiovascular system (often reversible after steroid use ceases)
Hepatic system
Reproductive system Males
Females
Dermatological system
Other systems
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Musculoskeletal
It is widely believed that a large increase in muscle mass associated with anabolic steroids can overwhelm the tendons and ligaments and lead to an increase in musculoskeletal injuries among users (Liow & Tavares, 1995). Adolescents who misuse anabolic steroids risk premature closure of epiphyses, leading to a reduction in final height.
Cardiovascular
There are numerous case reports of unexpected cardiovascular events in anabolic steroid users, and use has been linked to the development of hypertension, left ventricular hypertrophy, impaired diastolic filling and arrhythmia (Kutscher et al, 2002). The situation is further complicated by the effect of anabolic steroid use on lipid profile (Box 3
), and the use of diuretic drugs in combination with steroids (Table 2
). The effects of anabolic steroid use on thrombotic activity is also a risk factor, as platelet aggregation is increased in steroid users (Eisenberg & Galloway, 2005).
Gastrointestinal
Oral alkylated testosterone can cause primary biliary stenosis and cholestatic jaundice, and this may progress to hepatorenal syndrome. Anabolic steroid use may cause a reversible rise in aminotransferase levels, and may also increase the incidence of hepatic tumours in susceptible individuals (Eisenberg & Galloway, 2005).
Endocrine
Hyperandrogenism is associated with insulin resistance, although trial results are equivocal and may vary with the type of steroid used. For example, a direct correlation between methyltestosterone administration and insulin resistance has been demonstrated in non-obese women (Diamond, 1998), whereas other work has shown that neither testosterone nor nandrolone adversely affected insulin resistance in men (Hobbs et al, 1996).
Aromatisation is the process by which steroid hormones are interconverted. Testosterone and other aromatisable anabolic steroids are metabolised in part to oestradiol and other oestrogen agonists, and males using high doses of anabolic steroids can have the circulating oestrogen levels typical of women during a normal menstrual cycle (Wilson, 1988). This can lead to breast pain in men and gynaecomastia, which is one of the most frequently described side-effects of anabolic steroid use. Gynaecomastia is often irreversible. The effect of anabolic steroids on female breast tissue in the long term is not well studied, although some animal studies suggest that it may cause breast cell autolysis and necrosis (Blanco et al, 2002). Anabolic steroids suppress gonadotrophins, with variable effects on sexual interest, erectile function (causing spontaneous erections), the prostate and fertility. Testicular atrophy has been documented in control trials, and oligospermia may follow anabolic steroid use (Eisenberg & Galloway, 2005).
Supraphysiological doses of anabolic steroids in women lead to virilisation. Women taking steroids have reported voice instability (deepening of both projected speaking voice and singing voice), clitoral hypertrophy, shrinking breasts, menstrual irregularities, nausea and hirsuitism. Many of these side-effects are largely irreversible. Steroid use can also lead to cutaneous striae, acne and balding. There is a case report of secondary partial empty sella syndrome, with pituitary atrophy from negative feedback associated with the misuse of steroids together with growth and thyroid hormones (Dickerman & Jaikumar, 2001).
Other complications
Injecting is the predominant route of administration of anabolic steroids (80% in one study), and so users are at risk of contracting blood-borne viruses including hepatitis B and C and HIV (Brower et al, 1991). However, a study of 149 injectors of anabolic steroids in England enrolled between 1991 and 1996 showed that only 2% were hepatitis B core antibody positive, compared with 18% of intravenous heroin users and 12% of amphetamine users. None of the steroid users tested positive for HIV (Crampin et al, 1998).
| Dependence |
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Symptoms of steroid withdrawal include mood disorders (with suicidal depression as the most life-threatening complication), apathy, feelings of anxiety, difficulty in concentrating, insomnia, anorexia, decreased libido, fatigue, headache, and muscle and joint pain (Corrigan, 1996). It is often difficult to distinguish symptoms that are due to neuronal rebound in withdrawal from those that can be said to be psychological in origin. Observing oneself to lose muscle mass, strength, performance and confidence after cessation of steroid use has a powerful negative effect on mood, and this may lead to a strong desire to take steroids again.
Survey data have provided some evidence of the development of a full dependence syndrome in anabolic steroid users. In the above-mentioned study by Brower et al(1991), 28 (57%) met DSMIIIR criteria for dependence, based on responses to an anonymous self-administered questionnaire. Examination of the symptoms reported revealed features of both physical and psychological dependence, with some users reporting up to six of the DSMIIIR features of substance dependence.
Mechanisms of dependence
Various mechanisms have been suggested to explain the development of a dependence syndrome, including the effect of anabolic steroids on endogenous opioids or monoamine systems in the brain, and dependence resulting from social reinforcement of a muscular physical appearance. When enquiring about dependence, the psychiatrist must distinguish between the effects of steroid use and those of weight training, which may act as a confounding factor. For example, weight training, even in the absence of steroid use, may have a noticeable impact on lifestyle, as it can involve spending a lot of time in the gym and on a strict diet. However, only time actually spent on obtaining, using and recovering from the effects of the steroids meets the diagnostic criterion for dependence of spending large amounts of time on drug-related activities (Brower, 2002).
Links to other substance misuse
It has been suggested that anabolic steroid use may serve as a gateway to opioid misuse. In a study of lifetime drug use by 223 men admitted to a substance misuse treatment unit primarily for treatment of alcohol, cocaine and opioid dependence, 29 (13%) reported prior anabolic steroid use. Eighteen of these men reported that anabolic steroids were the first drugs that they had ever self-administered by injection, and seven men with opioid dependence reported that they first learned about opioids from friends at the gym, and subsequently first obtained opioids from the same person who had sold them anabolic steroids (Kanayama et al, 2003).
| Evaluation and treatment |
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Physical examination
The combination of muscular hypertrophy with testicular atrophy in males or virilisation in females is strongly suggestive of anabolic steroid use. However, there is a wide normal variation in the habitus of the population and the clinician must be aware of this in order to avoid an incorrect diagnosis of steroid use. For example, a normal teenage pubertal male may exhibit breast buds, small testes and cystic acne. Similarly, endocrine disorders may mimic harmful use of anabolic steroids: polycystic ovary disease and idiopathic hirsutism are highly relevant and treatable examples of this. Muscular hypertrophy and thin abdominal skin folds are among the most common findings in anabolic steroid users. Unusual injuries such as ruptured tendons, ligaments or muscles should also alert the clinician to possible steroid use (Eisenberg & Galloway, 2005). Unexplained or pronounced aggression may be the only obvious symptom or sign (Copeland et al, 2000). The use of other illicit drugs should always be considered.
Laboratory tests
Urine testing can confirm anabolic steroid use and be used as a measure of abstinence. Although these tests are common in competitive sports, they are not usually available from hospital laboratories as part of routine drug screenings in the clinical setting. In addition, their use as a screening method for evidence of drug cessation is complicated by the fact that many injectable steroids have long half-lives and are lipophilic, resulting in sequestration in adipose tissue and potential detection in urine a number of months after use. Alterations in liver transaminase levels, or an unsual low-/high-density lipoprotein cholesterol profile may also suggest anabolic steroid use.
Treatment
Very few anabolic steroid users enter treatment for dependence, and research evidence is limited. Treatment recommendations can be made on the basis of the treatment of other substance misuse disorders, along the lines of abstinence, treatment of withdrawal symptoms and maintenance (Eisenberg & Galloway, 2005). One important difference with steroid users is their emphasis on physical attributes, compared with other drug users who often begin to disregard their appearance as drug use becomes paramount. Thus, psychological interventions should encompass the physical aspect and help users to accept the loss of both idealised and realised physical attributes.
The role of pharmacotherapy is poorly defined. Medication for psychiatric symptoms should be based on a consideration of the risks and benefits, including its potential side-effects. Depressive symptoms are common during steroid withdrawal, and the use of antidepressants is indicated when symptoms persist and meet criteria for major depression. Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine have shown some promise in cases series (Malone & Dimeff, 1992). The SSRIs also have low potential for overdose, adverse cardiac effects and anticholinergic side-effects, all of which must be taken into account when treating people who have an increased risk for suicide, cardiotoxicity and prostatic hypertrophy. Antipsychotic drugs may be needed to treat persistent and marked irritability, aggressiveness or agitation.
| Conclusions |
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| Declaration of interest |
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MCQ answers
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