BASICS
The misuse of testosterone and closely related compounds (often in supratherapeutic dosages) to increase lean muscle mass and improve athletic performance
DESCRIPTION
- Anabolic-androgenic steroids (AAS) are medically indicated for the treatment of endocrine disorders such as primary or secondary hypogonadism. These agents increase muscle strength and lean muscle mass, which can alter physical appearance. This has led to the abuse of AAS (1). AAS include exogenous testosterone, synthetic androgens, synthetic androgen receptor modulators, androgen precursors, and other androgen stimulators.
- AAS are administered orally, transdermally, topically, or intramuscularly (2).
- When used in supraphysiologic doses, AAS contribute to muscle building and masculinization.
- Individuals typically "stack" steroids, using a cocktail of multiple agents at high doses and then discontinuing use for a period of weeks to reduce side effects and avoid detection (2).
- Side effects of AAS are typically dose-dependent. Some reverse when use is discontinued (3). There is growing concern over long-term side effects. (4)
- Many AAS's are purchased on the internet from unregulated sources (4). There are multiple street names ("roids" or "juice") for AAS.
- AAS use is not associated with an immediate "high" (seen with other drugs of abuse). Dependence is possible (5).
- AAS use is prohibited by the World Anti-Doping Agency (WADA) list. In 2010, AAS accounted for 60% of positive results in WADA laboratories (1). Testosterone, stanozolol, and nandrolone were the most frequent AAS identified (1).
- There is no evidence that AAS abuse or dependence develops from the therapeutic use of AAS.
EPIDEMIOLOGY
Incidence
Rates are difficult to estimate, as AAS use is typically concealed (3).
Prevalence
- Epidemiologic studies suggest that the lifetime prevalence of AAS use in men is at least 6.4% (6) and 1.6% in females (6).
- In power sports or weight lifting, the prevalence has been estimated to be as high as 10-50% (7).
- Past estimates suggest there are up to 3 million AAS users in the United States at any one time (3).
- Usage rates in men exceed those in women (5).
ETIOLOGY AND PATHOPHYSIOLOGY
- Natural testosterone is produced in small amounts by the adrenal gland and ovaries and in large amounts by the testes.
- AAS exert their anabolic effects through increased protein production, particularly in muscle cells.
- AAS decrease catabolism by blocking cortisol effects.
- Administration of exogenous testosterone suppresses the hypothalamic-pituitary-gonadal (HPG) axis, causing testicular atrophy and suppressed spermatogenesis. Human chorionic gonadotropin (hCG) is often used concurrently to mitigate this side effect (8).
- Aromatase inhibitors are concurrently used to counteract gynecomastia, which occurs with exogenous AAS use due to peripheral conversion of testosterone to estradiol.
- AAS use in adolescents accelerates cartilage formation, leading to premature epiphyseal closure (2).
- Muscle mass decreases after cessation of AAS use.
Genetics
Genetic variations in enzymatic and androgen receptor activity impacts AAS pharmacodynamics including anabolic and toxic effects (1).
RISK FACTORS
- Male gender (7)
- Age 20 to 30 years old (7)
- Participation in power sports (7)
- Use is more common in developed countries (8).
- Concurrent use of legal performance-enhancing substances (7)
- Use of alcohol and/or illicit drugs (7)
- Lower education level (3)
GENERAL PREVENTION
- There is insufficient evidence to recommend routine screening for anabolic steroid abuse (9).
- At-risk individuals should be counseled about negative side effects associated with AAS abuse (9).
COMMONLY ASSOCIATED CONDITIONS
- Major depressive disorder (10)
- Body dysmorphic disorder (10)
- Substance abuse (5)
DIAGNOSIS
- Based on history and physical exam
- The World Anti-Doping Association (WADA) uses the Athlete Biological Passport (ABP) as part of a comprehensive antidoping program to reveal the physiologic effects of doping (11).
- The WADA ABP tracks athletes' urine for an individuals' "steroid profile," which can be followed longitudinally (1,11)[C].
HISTORY
- Review patient risk (age, sports participation, body dysmorphism). If patients report use, ask about the specific product used and the duration, dosage, frequency, and route of usage.
- Ask about side effects, including impotence, mood disturbance, and amenorrhea in females.
- Ask about concurrent use of other substances, including over-the-counter (OTC) supplements, illegal drugs, alcohol, and prescription drug use (7,10)[C].
- Explore the social situation, including stressors and current support system.
- Determine preexisting medical and psychiatric conditions (10)[C].
- Body image: Discuss body dysmorphism (8,10)[C].
- Assess for suicidality.
PHYSICAL EXAM
- General
- Increased muscle mass
- Decreased body fat
- Deepening of voice and hirsutism in women
- Decreased height velocity in adolescents (2)
- Cardiovascular: hypertension
- Breast: gynecomastia
- Gastrointestinal: hepatomegaly
- Skin: acne, male pattern baldness, injection sites (buttocks, thighs, or deltoids)
- Genitourinary: testicular atrophy, clitoromegaly
- Psychiatric: anxiety, depression, mania, psychosis
DIFFERENTIAL DIAGNOSIS
- Cushing syndrome
- Congenital adrenal hyperplasia
- Adrenal neoplasm
- Polycystic ovarian syndrome
- Precocious puberty
- Drug-induced hirsutism
DIAGNOSTIC TESTS & INTERPRETATION
Determine presence of side effects of anabolic steroid usage and any comorbid medical conditions. Laboratory studies are not routinely performed, as they are limited by the timing of AAS administration. Results are often affected by advanced administration techniques in sophisticated users.
Initial Tests (lab, imaging)
- Urine testosterone: epitestosterone (T:E) ratio
- T:E ratio >3:1 suggests potential AAS abuse (1)[C].
- AAS abuse is associated with (2)[C]
- LDL increase
- HDL decrease
- AST, ALT, and gamma-glutamyltranspeptidase elevation
- Urinalysis to screen for proteinuria (12)[C]
- No imaging studies are required unless there is evidence of liver dysfunction.
- Echocardiography may be considered as clinically indicated. Routine echocardiography for all AAS users is not currently recommended (2).
Diagnostic Procedures/Other
- Renal function is often impacted due to increased muscle mass and frequent co-ingestion of creatine supplements (12).
TREATMENT
- Treatment is limited by the fact that AAS abusers rarely seek assistance (8).
- AAS abuse/dependence is complicated by
- High frequency of comorbid body image disorders including muscle dysmorphia (8,10)
- Few patients develop marked depressive symptoms upon withdrawal of AAS (4,8).
- Neurologic basis for dependence (possibly related to opioid receptors) needs to be overcome for sustained abstinence (5,10).
GENERAL MEASURES
Goal of therapy is to have patients acknowledge that anabolic steroid usage is detrimental to their health and to achieve long-term abstinence (8).
- Minimize withdrawal side effects and treat any comorbid psychiatric or substance abuse conditions (10)[C]. The primary side effect of withdrawal is often behavioral as patients struggle with loss of muscle mass.
- Assure adequate social support and coping mechanisms (10)[C].
MEDICATION
- Medications are limited to treating any underlying psychiatric illness and the clinical manifestations of hypogonadism (8)[C].
- Naltrexone, which blocks opioid-mediated positive reinforcement behaviors, has shown promise in animal studies (8).
- Available studies are limited by small sample size.
First Line
Depressive symptoms and body dysmorphism can be treated pharmacologically. SSRIs are the first-line agents of choice (8)[C]. Cognitive-behavioral therapy may alter negative thinking patterns (8)[C].
Second Line
- hCG may be used (through endocrinology consultation) to help accelerate endogenous testicular testosterone production (8)[C]. Hypogonadal treatment in young men should be tailored to maximize fertility potential (3)[C].
- Clomiphene supplementation may be used to stimulate pituitary function (3)[C].
- Less frequently, tamoxifen and phosphodiesterase inhibitors, such as sildenafil, are used to improve the symptoms of hypogonadism (3)[C].
- Severe depression that is refractory to medication and is associated with anabolic steroid discontinuation has been treated successfully with electroconvulsive therapy.
ISSUES FOR REFERRAL
- Endocrinology: prolonged hypothalamic-pituitary-gonadal-axis suppression, management of persistent symptoms of hypogonadism
- Psychiatry: psychosis, grandiosity, suicidal ideation
ADDITIONAL THERAPIES
- Cognitive-behavioral therapy
- Couples therapy
- Family therapy
INPATIENT CONSIDERATIONS
- Consider inpatient psychiatric hospitalization for patients with significant mood alterations or those who are an immediate threat to themselves or others.
- Inpatient treatment may be required for other complications of AAS abuse such as symptomatic cardiomyopathy or severe liver dysfunction.
ONGOING CARE
Follow-up with primary care and other specialists (e.g., behavioral health specialist or addiction specialist) is based on clinical factors.
FOLLOW-UP RECOMMENDATIONS
Based on side effects and comorbid psychiatric illness
PATIENT EDUCATION
- Substance Abuse and Mental Health Services Administration: https://findtreatment.samhsa.gov/ or 1-800-662-HELP
- National Center for Drug Free Sport, Inc: www.drugfreesport.com or 816-474-8655
- World Anti-Doping Agency: www.wada-ama.org/
PROGNOSIS
Most side effects resolve when AAS are discontinued. Prognosis is generally good. Long-term side effects are incompletely understood. ~30% of AAS abusers become chronic users. AAS use is more recalcitrant to treatment if polypharmacy is present (including concomitant use of legal dietary and sports supplements).
COMPLICATIONS
- Testicular atrophy; hypogonadism
- Clitoromegaly
- Decreased sperm count; decreased fertility index
- Impotence
- Premature epiphyseal closure in adolescents
- Hypertension; myocardial infarction; cardiomyopathy
- Sudden cardiac death
- Thrombosis
- Dyslipidemia
- Depression, suicide, violent behavior, anxiety, paranoia
- Substance abuse
- Hepatotoxicity, cholestasis, hepatocarcinoma
- Tendon rupture
- Hepatitis C, HIV, blood-borne illnesses
- Acne, male-pattern baldness, striae
- Profuse sweating
- Dysphonia
- Local injection site infections
REFERENCES
11 Rane A, Ekstr ¶m L. Androgens and doping tests: genetic variation and pit-falls. Br J Clin Pharmacol. 2012;74(1):3-15.22 Kersey RD, Elliot DL, Goldberg L, et al. National Athletic Trainers' Association position statement: anabolic-androgenic steroids. J Athl Train. 2012;47(5):567-588.33 Coward RM, Rajanahally S, Kovac JR, et al. Anabolic steroid induced hypogonadism in young men. J Urol. 2013;190(6):2200-2205.44 Nieschlag E, Vorona E. Doping with anabolic androgenic steroids (AAS): adverse effects on non-reproductive organs and functions. Rev Endocr Metab Disord. 2015;16(3):199-21155 Kanayama G, Hudson JI, Pope HGJr. Illicit anabolic-androgenic steroid use. Horm Behav. 2010;58(1):111-121.66 Nieschlag E, Vorona E. Mechanisms in endocrinology: medical consequences of doping with anabolic androgenic steroids: effects on reproductive functions. Eur J Endocrinol. 2015;173(2):R47-R58.77 Dodge T, Hoagland MF. The use of anabolic androgenic steroids and polypharmacy: a review of the literature. Drug Alcohol Depend. 2011;114(2-3):100-109.88 Kanayama G, Brower KJ, Wood RI, et al. Treatment of anabolic-androgenic steroid dependence: emerging evidence and its implications. Drug Alcohol Depend. 2010;109(1-3):6-13.99 Moyer VA. Primary care behavioral interventions to reduce illicit drug and nonmedical pharmaceutical use in children and adolescents: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2014;160(9):634-639.1010 Hildebrandt T, Lai JK, Langenbucher JW, et al. The diagnostic dilemma of pathological appearance and performance enhancing drug use. Drug Alcohol Depend. 2011;114(1):1-11.1111 Mazzoni I, Barroso O, Rabin O. The list of prohibited substances and methods in sport: structure and review process by the world anti-doping agency. J Anal Toxicol. 2011;35(9):608-612.1212 Herlitz LC, Markowitz GS, Farris AB, et al. Development of focal segmental glomerulosclerosis after anabolic steroid abuse. J Am Soc Nephrol. 2010;21(1):163-172.
ADDITIONAL READING
- Angoorani H, Narenjiha H, Tayyebi B, et al. Amphetamine use and its associated factors in body builders: a study from Tehran, Iran. Arch Med Sci. 2012;8(2):362-367.
- Eaton DK, Kann L, Kinchen S, et al. Youth risk behavior surveillance-United States, 2009. MMWR Surveill Summ. 2010;59(5):1-142.
- Lundmark J, G „revik N, Th ¶rngren JO, et al. Non-steroidal anti-inflammatory drugs do not influence the urinary testosterone/epitestosterone glucuronide ratio. Front Endocrinol (Lausanne). 2013;4:51.
SEE ALSO
Substance Use Disorders
CODES
ICD10
F55.3 Abuse of steroids or hormones
ICD9
305.90 Other, mixed, or unspecified drug abuse, unspecified
SNOMED
abuse of steroids (disorder)
CLINICAL PEARLS
- Anabolic steroid use is not limited to elite athletes.
- Suspect anabolic steroid abuse in at-risk patients with consistent clinical features.
- Discuss steroid use in an unbiased manner.
- Treat symptoms of withdrawal to help individuals remain abstinent.
- Psychosis, mania, violence, or severe depression are serious behavior consequences associated with AAS abuse.