Cholestasis secondary to anabolic steroid use in young menBMJ 2012; 344 doi: https://doi.org/10.1136/bmj.e468 (Published 02 February 2012) Cite this as: BMJ 2012;344:e468
All rapid responses
Autoimmune encephalitis (AI) has gained increasing recognition over recent years as a cause of acute psychiatric disturbance. The principal aetiologies appear to be anti-voltage gated potassium channel/leucine-rich glioma inactivated protein and anti-NMDA antibodies. Patients with AI usually require admission to a neurology ward for assessment and the administration of physical treatments which may include corticosteroids, plasma exchange, intravenous immunoglobulin, rituximab, cyclophosphamide, and oophorectomy. However, such patients often display a high level of psychiatric symptoms frequently associated with disturbed behaviour.1-3
On the basis of our clinical experience, we have developed increasing concern regarding the safety of the management of these aspects on non-psychiatric wards in the UK. Although these conditions are “organic”, the psychiatric manifestations may be similar to those seen in acute functional psychoses and require the expertise of psychiatrists and allied professionals and a safe physical milieu to ensure appropriate pharmacological and non-pharmacological behavioural management and any requirement for the invocation of the Mental Health Act. In our experience, the behavioural management of patients with AI on neurology wards is often fraught with difficulty and physical harm to them, fellow patients and staff has occurred.
It would not be feasible to place patients with AI in psychiatry units because of the need for clinical assessment and physical treatments outside the usual sphere of psychiatry. However, the separation of psychiatry from the rest of medicine in the UK means that psychiatric resources are often physically distanced from acute hospitals and the operational systems surrounding psychiatry and neurology are mutually unfamiliar. Nursing staff on neurology wards are not trained to manage acutely disturbed patients and medical staff may lack sufficient experience with acute sedation. In our experience, it is often not possible to obtain registered mental health nurses to provide one to one or higher ratio expert nursing. We are aware of multiple instances of the use of non-medically trained security guards in this situation but, in our view and experience, this is far from ideal. Provision of Liaison Psychiatry Services across the country is not consistent and even if a service is in place, there is not always the expertise to assist in management. Some large neuroscience centres have neuropsychiatric facilities capable of both the appropriate physical and psychiatric management of these patients but it is not possible to transfer all patients with AI to such centres at present.
We believe this problem deserves prompt attention, particularly as it seems likely that an increasing proportion of acute psychiatric illnesses will be found to be neurological and treatable. Possible steps towards resolving the current situation include the provision of acute medical/neurological beds within areas designed to minimise physical risk, increased psychiatric training for neurologists and neurological nurses, and increasing the availability of neuropsychiatric expertise and specialist neuropsychiatry units with staff trained in both mental and physical health care.
Dr Nicholas F Moran MBChB MRCP MSc, Consultant Neurologist, Kent & Canterbury Hospital, Canterbury, UK; Kings College Hospital, London, UK.
Dr Kirsten Lawson MBChB MRCPsych DGM, Consultant Liaison Psychiatrist and Clinical Lead for Liaison Psychiatry Services within Kent and Medway NHS and Social care Partnership NHS Trust.
Dr Neil Munro FRCP, DPhil, MB, BS, MRCP, Consultant Neurologist and Clinical Lead, Neurology, East Kent Hospitals; Kings College Hospital.
Professor Anthony S David FRCP, FRCPsych, MD, MSc, Professor of Cognitive Neuropsychiatry and Consultant Psychiatrist, Head of Section, Institute of Psychiatry, London, UK.
1. Lancet Neurol. 2008 Dec;7(12):1091-8. Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies. Dalmau J, Gleichman AJ, Hughes EG, Rossi JE, Peng X, Lai M, Dessain SK, Rosenfeld MR, Balice-Gordon R, Lynch DR.
2. Brain. 2004 Mar;127(Pt 3):701-12. Potassium channel antibody-associated encephalopathy: a potentially immunotherapy-responsive form of limbic encephalitis. Vincent A, Buckley C, Schott JM, Baker I, Dewar BK, Detert N, Clover L, Parkinson A, Bien CG, Omer S, Lang B, Rossor MN, Palace J.
3. Pollak TA, McCormack R, Peakman M, Nicholson TR, David AS. Prevalence of anti-N-methyl-d-aspartate (NMDA) antibodies in patients with schizophrenia and related psychoses: a systematic review and meta-analysis. Psychological Medicine (in press).
Competing interests: None
As Elsharkawy et al., note many anabolic steroid users take more than one steroid at a time in the belief that they will have additional and/or synergistic effects.  Many also use drugs to prevent and treat side effects arising from steroid use.  One drug that is commonly used in this respect is the anti-oestrogen tamoxifen which steroid users have used for more than 30 years to prevent and treat gynaecomastia. [2,3] This unwanted side effect is caused by an imbalance between androgens and oestrogens.  Usually, tamoxifen is sourced from the illicit market.  However, discussions on Internet bodybuilding forums have speculated that a product called “Esto Suppress” marketed as a “dietary supplement” contains tamoxifen as the label listed one of its chemical names: (Z)-1-(p-dimethylaminoethoxyphenyl)-1,2-diphenyl-1-butene (Figure). In order to investigate this, four samples of the product were purchased from a fitness equipment shop in Merseyside at different time points over a period of more than six months in late 2011 and early 2012. The content of the products were analysed using reference standards and gas chromatography techniques coupled with flame ionisation and mass spectrometry detectors.
Tamoxifen was identified in samples 1 (3.8 mg), 2 (0.9 mg) and 3 (3.0 mg) but was not detected in sample 4 (the final sample that was purchased). The product label suggested a dosage regimen of two capsules per day, which in the case of samples 1 and 3 may have provided a daily dose of 7.6 mg and 6 mg respectively. In comparison, 10–20 mg are used clinically for treating gynaecomastia.  It is not known whether the “Esto Suppress” product currently being sold contains tamoxifen.
Since the 2000s, a growing number of off-the-shelf products sold as “food”, “herbal” or “dietary supplements” aimed at the lifestyle market—such as gym goers, people looking to lose weight, or enhance their sex lives—have been found to contain pharmacologically active substances.  These include: anabolic steroids, growth hormones, aromatase inhibitors, erectogenics, stimulants, appetite suppressants, anxiolytics, diuretics and laxatives. [2,7] Some of these substances have been withdrawn from use in medicines due to safety concerns (e.g. the anorectic rimonabant) or they have never been tested in humans (e.g. the anabolic steroid methasterone). In many cases the substances are not listed on the labelling, and products may be marketed as “natural” exploiting the belief that such products are safer and healthier alternatives to synthetic substances.  In other cases, such as with “Esto Suppress”, only an obscure reference is made to the substance—such as a chemical name, which sometimes may be misspelled which is likely to have the effect of hiding the true ingredients from both consumers and regulators. Most users are likely to be unaware that they are taking these substances. Healthcare professionals should be aware of these developments, and, where relevant, ask their patients about any kind of “supplements” that they may use. In the UK, suspected adverse drug reactions should be reported through the yellow card scheme (https://yellowcard.mhra.gov.uk).
Figure. “Esto Suppress” that contained tamoxifen. The label of the product lists tamoxifen only by the chemical name (Z)-1-(p-dimethylaminoethoxyphenyl)-1,2-diphenyl-1-butene. The systematic name for tamoxifen is: (Z)-2-(4-(1,2-diphenylbut-1-en-1-yl)phenoxy)-N,N-dimethylethan-1-amine.
1. Elsharkawy AM, McPherson S, Masson S, Burt AD, Dawson RT, Hudson M. Cholestasis secondary to anabolic steroid use in young men. BMJ. 2012;344:e468.
2. Evans-Brown M, McVeigh J, Perkins C, et al. Human enhancement drugs. The emerging challenges to public health. Liverpool, North West Public Health Observatory, 2012. http://www.nwph.net/nwpho/Publications/Human%20Enhancement%20Drugs%20-%2....
3. Spano F, Ryan WG. Tamoxifen for gynecomastia induced by anabolic steroids? N Engl J Med 1984;311:861–2.
4. Nieschlag E, Behre HM, Nieschlag S, eds. Testosterone: action, deficiency, substitution. 4th edn. Cambridge, Cambridge University Press, 2012.
5. Thevis M, Schrader Y, Thomas A, et al. Analysis of confiscated black market drugs using chromatographic and mass spectrometric approaches. J Anal Toxicol 2008;32:232–40.
6. Kunath F, Keck B, Antes G, Wullich B, Meerpohl JJ. Tamoxifen for the management of breast events induced by non-steroidal antiandrogens in patients with prostate cancer: a systematic review. BMC Med 2012;10:96.
7. Food and Drug Administration. Tainted_Supplements_CDER. http://www.accessdata.fda.gov/scripts/sda/sdNavigation.cfm?filter=&sortC...
8. Ipsos MORI. Public perceptions of herbal medicine. General public qualitative & quantitative research. Ipsos MORI 2008.
Michael Evans-Brown (a*), Andreas Kimergård (b), Jim McVeigh (c), Martin Chandler (d), Simon D. Brandt (e)
(a) scientific analyst, European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), Lisbon, Portugal
(b) visiting lecturer, Centre for Public Health, Liverpool John Moores University, 15–21 Webster Street, Liverpool, L3 2ET, United Kingdom
(c) deputy director, Centre for Public Health, Liverpool John Moores University, 15–21 Webster Street, Liverpool, L3 2ET, United Kingdom
(d) human enhancement drugs researcher, Centre for Public Health, Liverpool John Moores University, 15–21 Webster Street, Liverpool, L3 2ET, United Kingdom
(e) reader in bioactive drug chemistry, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, L3 3AF, United Kingdom
*Correspondance to Michael.Evans-Brown[AT]emcdda.europa.eu
Competing interests: No competing interests
The authors of this report are to be congratulated for addressing an important issue of public health. Anabolic steroid abuse is likely to be more prevalent than the studies report. Authors quote that a
study of homosexual men who regularly attended gyms in London in 2000 found that 15.2% of the 792 men surveyed had used anabolic steroids in the preceding year, with 11.7% of them having injected the drugs(1). What is interesting about this study is that 24.3 % of men had taken steroids for medical reasons than other (5.9%). It might be worth investigating if men with HIV are more prone to developing side effects with steroids.
1.Bolding G, Sherr L, Elford J. Use of anabolic steroids and associated health risks among gay men attending London gyms. Addiction2002;97:195-203
Competing interests: No competing interests
I was pleased to see that the important issue of anabolic steroid use was highlighted in Elsharkawy et al’s recent article (1). Rates of anabolic steroid use is increasing which has occurred alongside changes in male body image and rising rates of eating disorders in young men and boys (2). This is partly a consequence of the glamorisation of the male body over the last thirty years with an overemphais on the need for muscularity with men being increasingly confronted with similar impossible body ideals that have long been faced by women. As a result body image objectification and body dissatisfaction have become increasingly common in young men and boys who often turn to anabolic steroids as a quick solution to achieving and maintaining the ideal body with little concern for the psychological and physical consequences that this entails.
In parallel to to these changes the condition known as ‘muscle dysmorphia’ (also known as ‘bigorexia’ or ‘reverse anorexia’) has emerged. Muscle dysmorphia is characterised by a preoccupation with overall muscularity and a drive to gain weight without gaining fat. Behavioural manifestations include anabolic steroid misuse and excessive exercise as a means to achieving ‘bigness’ and there is an association with marked functional deficits in terms of social avoidance and occupational functioning. Interestingly the core psychopathology and behavioural features of the man with muscle dysmorphia mirror the phenomenology of the woman with an eating disorder in her pursuit oif thinness. Whilst muscle dysmorphia was initially described in a cohort of male body builders in the USA twenty years ago (3), this condition is being increasingly seen in young men and boys who are not involved in competitive sport.
Muscle dysmorphia should be suspected in any patient presenting with the psychological or physical sequelae of anabolic steroid use and clinicans should consider referring such patients to psychiatric or specialist eating disorders services for further assessment and possible treatment.
1. Elsharkawy AM, McPherson S, Masson S, et al. Cholestasis secondary to anabolic steroid use in young men. BMJ 2012;344:e468.
2. Jones WR, Morgan JF. Eating diosrders in men: a review of the literature. Journal of Public Mental Health 2010; 9(2): 23-31.
3. Pope HG, Katz DL, Hudson JI. Anorexia nervosa and ‘reverse anorexia’ among 108 male bodybuilders. Comprehensive Psychiatry 1993; 34(6): 406-409.
Competing interests: No competing interests