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ANABOLIC STEROIDS

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Anabolic steroids have been placed into Schedule III of the Controlled Substances Act.

Specific Substances

    A) Ethylestrenol (Oral)
    1) 19-Nor-17alpha-pregn-4-en-17-ol
    2) CAS 965-90-2
    Fluoxymesterone (Oral)
    1) 9-Fluoro-11,17-dihydroxy-17-methylandrost-4-en-3-one
    2) CAS 76-43-7
    Methandrostenolone (Oral)
    1) 17-Hydroxy-17-methylandrosta-1,4-dien-3-one
    2) CAS 72-63-9
    methylTESTOSTERone (Oral)
    1) 17-Hydroxy-17-methylandrost-4-en-3-one
    2) CAS 58-18-4
    Oxandrolone (Oral)
    1) 17-Hydroxy-17-methyl-2-oxandrostan-3-one
    2) CAS 53-39-4
    Oxymetholone (Oral)
    1) 4,17-Dihydroxy-17-methylandrost-4-en-3-one
    2) CAS 434-07-1
    Stanozolol (Oral)
    1) 17-Methyl-2'H-androst-2-eno(3,2-c)-pyrazol-17-ol
    2) CAS 10418-03-8
    Mesterolone (Oral)
    1) 17-Hydroxy-1-methylandrostan-3-one
    2) CAS 1424-00-6
    Nandrolone Decanoate (Injectable)
    1) 17beta-((1-Oxodecyl)oxy)-estr-4-en-3-one
    2) CAS 360-70-3
    Nandrolone Phenpropionate (Injectable)
    1) (17beta)-(1-Oxopropoxy)estr-4-en-3-one
    2) CAS 60-90-8
    Testosterone Cypionate (Injectable)
    1) 17beta-(3-Cyclopentyl-1-oxopropoxy)androst-
    2) 4-en-3-one
    3) CAS 58-20-8
    Testosterone Enanthate (Injectable)
    1) 17-((1-Oxoheptyl)oxy)-androst-4-en-3-one
    2) CAS 315-37-7
    Testosterone Propionate (Injectable)
    1) Delta4-Androstene-17beta-propionate-3-one
    2) CAS 57-85-2
    Boldenone (Veterinary Injectable)
    1) 17-Hydroxyandrosta-1,4-dien-3-one
    2) CAS 846-48-0

    1.2.1) MOLECULAR FORMULA
    1) FLUOXYMESTERONE: C20H29FO3
    2) METHYLTESTOSTERONE: C20H30O2
    3) NANDROLONE DECANOATE: C28H44O3
    4) OXANDROLONE: C19H30O3
    5) TESTOSTERONE: C19H28O2
    6) TESTOSTERONE CYPIONATE: C27H40O3
    7) TESTOSTERONE ENANTHATE: C26H40O3
    8) TESTOSTERONE UNDECANOATE: C30H48O3

Available Forms Sources

    A) FORMS
    1) As oral tablets, elixir, and parenteral dosage forms.
    2) Ethylestreno2 - Maxibolin(R) (Organon)
    a) 2 mg tablets; Elixir - 2 mg/5 mL
    3) Fluoxymesterone - Halotestin(R) (Upjohn), Android-F(R) (ICN Pharm)
    a) 2, 5, and 10 mg tablets
    4) Methandriol Dipropionate - Stenediol(R) (Organon, UK)
    5) Methandrotenolone - Dianabol(R) (Ciba) (discontinued)
    6) MethylTESTOSTERone - Android-10(R), Android-5(R), Android-15(R) (ICN Pharm), Metandren(R) (Ciba), Oreton Methyl(R) (Schering), Testred(R) (ICN), and Virilon(R) (Star)
    a) Capsules - 10 mg; 5, 10, and 25 mg tablets
    7) Nandrolone decanoate - Deca-Durabolin(R) (Organon) Hybolin Decanoate(R) (Hyrex), Neo-Durabolic(R) (Hauck)
    a) Injectable (In Oil) - 50 mg/mL, 100 mg/mL, and 200 mg/mL
    8) Nandrolone phenpropionate - Durabolin(R), Durabolin-50(R) (Organon), Anabolin(R) (Alto), Nandrobolic(R) (Forest), Hybolin Improved (R) (Hyrex)
    a) Injectable (In Oil) - 25 mg/mL and 50 mg/mL
    9) Oxandrolone - Anavar(R) (Searle) and Anadrol-50(R) (Searle)
    a) 2.5 mg tablets
    10) Oxymetholone - Anadrol-50(R) (Syntex)
    a) 50 mg tablets
    11) Stanozolol - Winstrol(R) (Winthrop Pharmaceutical)
    a) 2 mg tablets
    12) Boldenone (Equipoise(R)) is a veterinary injectable preparation containing 25 or 50 mg/mL.
    B) USES
    1) Anabolic steroids are used to enhance athletic performance (Kennedy, 2000).
    a) ADOLESCENT FREQUENCY OF USE: In a large questionnaire study of 3403 US male 12th graders, 6.6% admitted to using anabolic steroids illicitly. 66% of the users started on steroids at age 16 or younger. 44% "stack" or use multiple anabolic steroids, often in cycles lasting 6 to 12 weeks. 35% of users were not involved in any sport at school, indicating widespread use to enhance appearance (Buckley et al, 1988).
    b) More recent studies of US adolescents suggest that lifetime anabolic steroid use is in the range of 0.2% to 3.7% overall (0.3% to 5% in males and 0.1% to 2.4% in females) (Yesalis et al, 1997).
    2) Anabolic steroids have been placed into Schedule III of the Controlled Substances Act.

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Anabolic steroids are compounds that increase muscle mass. They include natural androgens such as testosterone as well as synthetic androgens such as stanozolol and nandrolone. Medical indications for testosterone include hypogonadism, delayed puberty, and breast cancer in females. Available formulations include capsules, transdermal and transbuccal formulations, intramuscular injections, and subcutaneous implantations.
    B) PHARMACOLOGY: Endogenous androgens promote the growth and development of the male sex organs as well as maintaining secondary sex characteristics. Higher doses promote muscle mass and strength and increasing production of erythropoietin and subsequent increase in red blood cell production. In addition, they may cause growth of facial and body hair, baldness, and increased sex drive and aggression.
    C) TOXICOLOGY: Toxicity from anabolic steroids is a result of their androgenic and anabolic processes.
    D) EPIDEMIOLOGY: As these substances are often used in a clandestine manner, it is difficult to know how commonly anabolic steroids are used/abused. However, it is known that they have been used by professional athletes, adolescents playing sports, as well as older people for "anti-aging" properties. Acute overdose is extremely rare.
    E) WITH THERAPEUTIC USE
    1) CHRONIC USE: Severe acne, baldness, high blood pressure and heart disease, headaches, strokes, mood swings and aggressive behavior, reduced sperm count, impotence, testicular atrophy, enlarged prostate leading to urinary problems, increased risk of tendon injuries, arthralgias, and virilization in women (reduced breast size, enlarged clitoris, increased facial and body hair, deepened voice, and menstrual problems).
    2) SERIOUS EFFECTS: Deep venous thrombosis and strokes, extreme aggressive behavior, electrolyte changes, hepatitis and hepatic dysfunction, and anaphylactoid reactions.
    3) LOCAL EFFECTS: Effects from the transdermal system include pruritus at the application site (37%) and burn-like blisters (12%). Rarely, erythema, vesicles, allergic contact dermatitis, burning, and induration at the application site of the transdermal system may occur. Complications from transbuccal administration include gum edema, gum or mouth irritation, gum pain and tenderness, and taste perversions.
    F) WITH POISONING/EXPOSURE
    1) Toxicity from acute overdose is unlikely; however, chronic exposure to high doses may result in adverse effects.
    0.2.20) REPRODUCTIVE
    A) Methandrostenolone has been shown to inhibit placental glucose-6-phosphatase in humans.
    B) Administration of anabolic steroids during gestation may result in masculinization of the urogenital sinus and clitoral hypertrophy. Premature bone maturation and decreased birthweight have been reported. Testosterone is contraindicated in women who are pregnant or who may become pregnant while taking the medication. Due to the potential for serious adverse effects to the infant from exposure to testosterone, breastfeeding is contraindicated.
    C) Danazol, esterified estrogens/methylTESTOSTERone, and testosterone are classified as FDA pregnancy category X .
    0.2.21) CARCINOGENICITY
    A) Fatal and benign hepatomas, adenocarcinoma of the prostate and sigmoid colon, Wilms tumor, hepatic angiosarcoma, and acute myeloid leukemia have been reported with anabolic steroids. Linkage between malignancies and abuse has not been clearly established.

Laboratory Monitoring

    A) Monitor vital signs, particularly blood pressure. Monitor ECG in patients with cardiac symptoms or severe hypertension.
    B) Monitor liver enzymes, serum electrolytes, blood glucose, hemoglobin and hematocrit.
    C) PEDIATRIC: Obtain long bone radiographs to document the premature closure of the epiphysis in cases where children/adolescents have chronically used anabolic steroids.
    D) Gas chromatography-mass spectrometry analysis for specific anabolic steroid detection/levels can be performed, but are not readily available and are not clinically useful.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Acute toxicity is extremely rare from these compounds, except perhaps local effects from transdermal and transbuccal administration. In terms of care for chronic use, the most immediate treatment would be cessation of use and then supportive care for associated symptoms.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Acute toxicity from anabolic steroid use is not expected, and the mainstay of treatment would be cessation of use and supportive care of symptoms. Extreme aggression may require treatment with benzodiazepines and antipsychotics.
    C) DECONTAMINATION
    1) PREHOSPITAL: There is no role for prehospital decontamination for this exposure.
    2) HOSPITAL: In general, decontamination is not indicated for this overdose. Activated charcoal could be considered for acute overdose with significant co-ingestions if the patient is awake and cooperative and if the ingestion was relatively recent. There is no role for the use of lavage, whole bowel irrigation or multiple doses of charcoal.
    D) AIRWAY MANAGEMENT
    1) Ensure adequate ventilation and perform endotracheal intubation early in patients with serious cardiac toxicity.
    E) ANTIDOTE
    1) There is no specific antidote for anabolic steroids.
    F) DRUG WITHDRAWAL
    1) Similar to other agents appropriate drug detoxification and recovery therapy.
    G) AGGRESSIVE BEHAVIOR
    1) Treat with IV benzodiazepines or antipsychotics.
    H) ENHANCED ELIMINATION
    1) There is no role for dialysis, hemoperfusion, urinary alkalinization, or multiple dose charcoal for anabolic steroid use.
    I) PATIENT DISPOSITION
    1) HOME CRITERIA: Patients with unintentional exposures can be watched at home with follow up with their regular physician as needed.
    2) OBSERVATION CRITERIA: Patients with significant adverse effects should be sent to a healthcare facility for treatment of their symptoms and should not be sent home until the symptoms are treated or resolved.
    3) ADMISSION CRITERIA: Patients with severe adverse reactions (eg, strokes) should be admitted, and depending on the severity of their symptoms, may merit an ICU admission. Criteria for discharge include resolution or treatment of their symptoms.
    4) CONSULT CRITERIA: The appropriate consultant should be called as needed (eg, neurologist for strokes, etc.). Consult a medical toxicologist or Poison Center for assistance in managing patients with severe toxicity or in whom the diagnosis is unclear.
    J) PITFALLS
    1) Acute toxicity is rare, but anabolic steroid use may be missed if not considered as many people use them surreptitiously, and there can be issues with the quality control of illicit products as well as heightened risk of infections (eg, bacterial endocarditis, HIV) from intravenous use and/or sharing of needles.
    K) PHARMACOKINETICS
    1) Duration of action depends on the formulation and route of ingestion. Testosterone gel usually lasts 24 to 48 hours while the cypionate and enanthate esters have durations for up to 4 weeks after an intramuscular injection. Transdermal absorption is approximately 10% of an applied dose. Testosterone is 98% protein bound to both sex hormone-binding globulin and albumin. There is hepatic metabolism of anabolic steroids, and the half life of elimination can vary from 10 minutes to weeks. Excretion is primarily through the urine (90%) with some minor fecal excretion as well.
    L) PREDISPOSING CONDITIONS
    1) Contraindications to the use of anabolic steroids include patients with breast or prostate cancer, nephritis, cardio-renal failure, hepatic disease with impaired bilirubin excretion, and pregnancy. Patients with benign prostatic hyperplasia, edematous conditions, and sleep apnea may have worsening symptoms. In the elderly, anabolic steroids should be used with great caution as there may be a higher risk for prostatic hyperplasia, prostate cancer, fluid retention, and transaminitis. In children, anabolic steroids may accelerate bone maturation without compensatory gain in linear growth.
    M) DIFFERENTIAL DIAGNOSIS
    1) The differential diagnosis for some of the adverse reactions from the use of anabolic steroids (eg, stroke) can be quite large. However, there are some malignancies that can secrete steroid hormones and might mimic anabolic steroid use.
    0.4.6) PARENTERAL EXPOSURE
    A) Overdose of parenteral anabolic steroids is expected to produce the same effects as overdose with the oral formulation. See ORAL EXPOSURE for further information.

Range Of Toxicity

    A) TOXICITY: A toxic dose has not been established.
    B) THERAPEUTIC DOSE: ADULT: Varies with drug and indication. FLUOXYMESTERONE: 2.5 to 20 mg orally daily in androgen-deficient males. METHYLTESTOSTERONE: 10 to 50 mg orally daily in androgen-deficient males; 50 to 200 mg orally daily as palliative treatment in women with metastatic breast cancer. OXANDROLONE: 2.5 to 20 mg orally daily in 2 to 4 divided doses. TESTOSTERONE: Transdermal patch, 2 to 6 mg/day; Topical gel (1%), 5 to 10 g once daily; Topical gel (1.62%), 20.25 to 81 mg once daily; Nasal gel, 11 mg three times daily (MAX dose: 33 mg); IM (testosterone cypionate and enanthate), 50 to 400 mg IM every 2 to 4 weeks. PEDIATRIC: Varies with drug and indication. FLUOXYMESTERONE: 2.5 to 20 mg orally daily. METHYLTESTOSTERONE: 10 to 50 mg orally daily. OXANDROLONE: Less than or equal to 0.1 mg/kg total daily dose, may be repeated intermittently as indicated. TESTOSTERONE (transdermal): Safety and efficacy have not been established in pediatric patients. TESTOSTERONE CYPIONATE (12 years and older): 50 to 400 mg IM every 2 to 4 weeks. TESTOSTERONE ENANTHATE: 50 to 400 mg IM every 2 to 4 weeks.

Clinical Effects

Summary Of Exposure

    A) USES: Anabolic steroids are compounds that increase muscle mass. They include natural androgens such as testosterone as well as synthetic androgens such as stanozolol and nandrolone. Medical indications for testosterone include hypogonadism, delayed puberty, and breast cancer in females. Available formulations include capsules, transdermal and transbuccal formulations, intramuscular injections, and subcutaneous implantations.
    B) PHARMACOLOGY: Endogenous androgens promote the growth and development of the male sex organs as well as maintaining secondary sex characteristics. Higher doses promote muscle mass and strength and increasing production of erythropoietin and subsequent increase in red blood cell production. In addition, they may cause growth of facial and body hair, baldness, and increased sex drive and aggression.
    C) TOXICOLOGY: Toxicity from anabolic steroids is a result of their androgenic and anabolic processes.
    D) EPIDEMIOLOGY: As these substances are often used in a clandestine manner, it is difficult to know how commonly anabolic steroids are used/abused. However, it is known that they have been used by professional athletes, adolescents playing sports, as well as older people for "anti-aging" properties. Acute overdose is extremely rare.
    E) WITH THERAPEUTIC USE
    1) CHRONIC USE: Severe acne, baldness, high blood pressure and heart disease, headaches, strokes, mood swings and aggressive behavior, reduced sperm count, impotence, testicular atrophy, enlarged prostate leading to urinary problems, increased risk of tendon injuries, arthralgias, and virilization in women (reduced breast size, enlarged clitoris, increased facial and body hair, deepened voice, and menstrual problems).
    2) SERIOUS EFFECTS: Deep venous thrombosis and strokes, extreme aggressive behavior, electrolyte changes, hepatitis and hepatic dysfunction, and anaphylactoid reactions.
    3) LOCAL EFFECTS: Effects from the transdermal system include pruritus at the application site (37%) and burn-like blisters (12%). Rarely, erythema, vesicles, allergic contact dermatitis, burning, and induration at the application site of the transdermal system may occur. Complications from transbuccal administration include gum edema, gum or mouth irritation, gum pain and tenderness, and taste perversions.
    F) WITH POISONING/EXPOSURE
    1) Toxicity from acute overdose is unlikely; however, chronic exposure to high doses may result in adverse effects.

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) CARDIOVASCULAR FINDING
    1) WITH POISONING/EXPOSURE
    a) A study comparing vascular stiffness, vascular function, and cardiovascular risk factors between active abusers of anabolic steroids, previous abusers with a 3-month washout period, and supplement-free bodybuilders revealed impaired vascular reactivity associated with anabolic steroids that resolved after a period of discontinuation (Lane et al, 2006).
    B) MYOCARDIAL INFARCTION
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 22-year-old weightlifter with no previous or family history of heart disease developed an acute myocardial infarction following use of intramuscular and oral anabolic steroids for 6 weeks (McNutt et al, 1988).
    1) Coronary arteries were patent, serum cholesterol was markedly elevated (596 mg/dL), and platelet hyperaggregability was present. Repeat studies 12 to 24 days after discontinuation of the steroids revealed a serum cholesterol of 283 mg/dL and normal platelet aggregation.
    b) CASE REPORT: A 39-year-old HIV infected man sustained a myocardial infarction 8 months after beginning intramuscular testosterone injections. Serum cholesterol and LDL were elevated with a normal HDL (previous lipid profile had been normal), and angiography revealed a ruptured plaque and a nonocclusive thrombus of the mid-left anterior descending artery. He also had a family history of CAD and was a smoker (Varriale et al, 1999).
    1) Anabolic steroid use has been linked to myocardial infarction in at least 8 other cases, usually involving young athletes often with normal coronary arteries (Varriale et al, 1999).
    c) CASE REPORT: A 44-year-old man sustained an acute inferior myocardial infarction associated with severe polycythemia secondary to testosterone abuse. His hemoglobin and hematocrit upon presentation were 22 g/dl and 63%, respectively. Cardiac catheterization revealed diffuse disease of the left anterior descending artery with 95% occlusion at the takeoff or a small septal branch, and total occlusion of the mid portion of the right coronary artery with a thrombus. He was treated with percutaneous transluminal coronary angioplasty and stent placement in the mid and distal right coronary arteries and was phlebotomized until his hematocrit reached 45% (Stergiopoulos et al, 2008).
    C) DEAD - SUDDEN DEATH
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 32-year-old male bodybuilder was unable to be resuscitated following a loss of consciousness while weight lifting. Two weeks earlier he reported chest pain that lasted a few minutes but was not seen by a physician. Autopsy showed an area of necrosis involving 20% of the left ventricular myocardial mass and normal coronary arteries (Fineschi et al, 2001).
    b) CASE REPORT: Sudden cardiac death occurred in a 21-year-old, previously healthy weightlifter after several months of biweekly parenteral anabolic steroid use. Autopsy revealed marked cardiac and renal hypertrophy with focal myocardial fibrosis and necrosis. A direct cause-effect relationship was not clearly established (Luke et al, 1990).
    c) CASE REPORT: A 41-year-old bodybuilder who had used multiple steroids continuously for the past 3 years was admitted to the hospital and diagnosed with congestive heart failure. In junior high school, he had been told during a routine sports physical that he had an "enlarged heart" but had no health problems until the current episode. Six weeks after release from the hospital, the patient died in his sleep. Postmortem examination revealed oligospermia, cardiac enlargement, myofibrillar hypertrophy, and patchy areas of myocardial fibrosis (Ferenchick et al, 1991).
    d) CASE REPORT: A 28-year-old man died following long-term anabolic steroid abuse. Symptoms preceding his death included dyspnea, peripheral edema, and increases in bodyweight of 3 kg/day. Two years prior to death, his echocardiogram showed septal hypertrophy and a left-ventricular diameter of 60 mm. Necropsy showed hypertrophy of heart, liver, and kidney. Extensive signs of chronic heart insufficiency and massive atherosclerosis were evident (Madea & Grellner, 1998).
    D) CARDIOMYOPATHY
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 40-year-old man, with a 10-year history of anabolic steroid abuse, presented with coagulopathy, hepatic failure, and hyponatremia secondary to asymptomatic cardiomyopathy and thrombus. Standard treatment of hyponatremia revealed symptoms of heart failure and pulmonary congestion that were otherwise not noted on physical exam when the patient presented to the hospital. Echocardiogram revealed dilated cardiomyopathy with an ejection fraction of 15%, and a large thrombus in both cardiac ventricles. The patient's hepatic function started to improve after his cardiomyopathy was aggressively treated with dopamine, dobutamine, and diuresis. Anticoagulants were initiated after the patient's INR fell to less than 2.0 (Bispo et al, 2009).
    E) HYPERTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 28-year-old man developed arterial hypertension (210/120 mmHg) after 13 years of anabolic steroid abuse (Madea & Grellner, 1998).
    b) CASE REPORT: A 65-year-old man developed hypertension and polycythemia (hematocrit 55.5% to 58.5%) after topical testosterone to his scrotum daily for 5 years (estimated dose 10 milligrams testosterone/day). Polycythemia and hypertension resolved when testosterone was discontinued (Tangredi & Buxton, 2001).
    F) VENTRICULAR HYPERTROPHY
    1) WITH POISONING/EXPOSURE
    a) In a study of cardiac effects of chronic anabolic androgenic steroid (AAS) use, 17 athletes who were currently abusing AAS (mean dose 1030 mg/week for 33 weeks/year over 8 years), were compared to 15 athletes who had stopped AAS abuse for at least 1 year (mean 43 months; range 12 months to 10 years; mean dose 720 mg/week for 26 weeks/year over 9 years) and 15 weightlifters who had never abused AAS. Systolic blood pressure was higher in athletes currently using AAS than in former or never users. Current and former users of AAS had slight concentric left ventricular hypertrophy compared with athletes who had never used AAS, reflected by higher LV muscle mass and wall thickness related to fat free body mass, and a higher ratio of LV wall thickness to internal diameter(Urhausen et al, 2004).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CHOREOATHETOSIS
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: Mental confusion and choreiform movements were described in a 66-year-old man following therapeutic use of oxymetholone 200 to 300 mg/day for aplastic anemia (Tilzey et al, 1981).
    B) SPASMODIC MOVEMENT
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: Two athletes with a history of Gilles de la Tourette syndrome reported that their tic symptoms worsened during periods of anabolic steroid use (Leckman & Scahill, 1990).
    C) CEREBROVASCULAR ACCIDENT
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 21-year-old man who had been using ethylestrenol 6 to 8 milligrams daily for 6 weeks developed an ischemic cerebrovascular accident in the region of the right basal ganglia and internal capsule (Akhter et al, 1994). Angiography demonstrated occlusion of the right anterior and middle cerebral arteries. Clinical effects included a generalized tonic-clonic seizure followed by dense left hemiplegia and hemisensory impairment with a positive Babinski sign on the left. He had no other risk factors for CVA.
    b) CASE REPORT: A 26-year-old man who had been using stanozolol 10 mg daily for 3 months developed a posterior territory ischemic stroke. Clinical effects included a global headache, vomiting, and unconsciousness prior to presentation to the hospital. The patient also developed decerebration posture, anisocoria (mild dilated and fixed left pupil) and left eye palsy. No abnormalities were found on MRI angiography of the neck, digital cerebral angiography, or echocardiogram. He was left severely disabled with right hemiparesis, spasticity, and hyperreflexia, mixed aphasia, severe dysarthria, and limitation of extraocular movements (Santamarina et al, 2008).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) VOMITING
    1) WITH THERAPEUTIC USE
    a) Nausea and vomiting may be noted (Kibble & Ross, 1987).
    B) ESOPHAGEAL VARICES
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Bleeding esophageal varices were reported in a 30-year-old weightlifter after taking 3 anabolic steroids for 18 months. The steroid doses were up to 6 times therapeutic recommendations; stanazolol 15 mg, methandienone 15 mg, and oxandrolone 7.5 mg daily (Winwood et al, 1990).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) LIVER ENZYMES ABNORMAL
    1) WITH THERAPEUTIC USE
    a) AST and ALT may be elevated during intense athletic training from the breakdown of skeletal muscle (Strauss et al, 1982).
    b) CASE REPORT: Hepatic enzyme levels were elevated in a 28-year-old man following long-term administration of anabolic steroids, monitored 2 years before his death. Necropsy revealed liver hypertrophy (5710 grams) (Madea & Grellner, 1998).
    B) TOXIC HEPATITIS
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: 26-year-old male bodybuilder presented with a 10-day history of nausea, malaise, and jaundice and was found to have toxic hepatitis due to hepatocellular necrosis (Stimac et al, 2002).
    b) CASE REPORT: A 40-year-old man, with a 10-year history of anabolic steroid abuse, presented with coagulopathy (INR 3.3, factor V 15%), hepatic failure (AST 7897 international units/liter, ALT 7125 international units/L, total bilirubin 6.8 mg/dL, ammonia 73 micromol/L, lactate dehydrogenase 7140 international units/L) and hyponatremia, cardiomyopathy and intraventricular thrombus. Standard treatment of hyponatremia provoked symptoms of heart failure and pulmonary congestion that were otherwise not noted on physical exam when the patient presented to the hospital. Echocardiogram revealed dilated cardiomyopathy with an ejection fraction of 15%, and a large thrombus in both cardiac ventricles. The patient's hepatic function started to improve after his cardiomyopathy was aggressively treated with dopamine, dobutamine, and diuresis. Anticoagulants were initiated after the patient's INR fell to less than 2.0 (Bispo et al, 2009).
    C) CHOLESTATIC HEPATITIS
    1) WITH POISONING/EXPOSURE
    a) Hepatomas and peliosis hepatis have been associated with prolonged use of high-dose anabolic steroids (Frankle et al, 1984; Haupt & Rovere, 1984; Overly et al, 1984).
    b) CASE REPORT: MethylTESTOSTERone-induced cholestatic jaundice was reported in a 64-year-old man receiving 20 to 40 mg of methylTESTOSTERone daily for 6 months for impotence (Hartleb & Nowak, 1990; Borhan-Manesh & Farnum, 1989).
    c) CASE REPORTS: Hepatotoxicity was reported in 2 patients who were taking anabolic steroids on a daily basis for several weeks as part of their bodybuilding regimen. Both patients experienced jaundice, weakness, pruritus, and weight loss of 17 to 30 pounds. Laboratory analyses revealed elevated liver enzyme and bilirubin concentrations, and liver biopsies showed lobular cholestasis with inflammation. Both patients recovered with supportive treatment (Kafrouni et al, 2007).
    D) HEPATOCELLULAR ADENOMA
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: A 35-year-old man using steroids for 15 years was asymptomatic on presentation, but was subsequently found to have 2 lesions (6 cm and 12 cm) on ultrasound which were found to be adenomas on MRI and cytology. The second patient, a 23-year-old male bodybuilder using anabolic steroids and a loop diuretic for 6 months, presented to the emergency department in a confused state and was found to have renal failure, muscle damage, hypernatremia, and a metabolic alkalosis. Ultrasound displayed mild hepatomegaly with multiple hyperechogenic nodules that did not reveal malignancy on aspiration (Socas et al, 2005).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) DISORDER OF TESTIS
    1) WITH POISONING/EXPOSURE
    a) HYPOGONADISM
    1) CASE SERIES: In a study of 23 hemodialysis patients who were taking anabolic steroids therapeutically, the only significantly altered variable compared with controls was a decreased testosterone level. One of the patients experienced decreased testicular size and aspermia, which resolved after discontinuation of the steroid and administration of human chorionic gonadotropin (Maeda et al, 1989).
    2) CASE REPORT: A 28-year-old man developed secondary hypogonadism with decreased testosterone levels (3.4 mcg/L) after long-term anabolic steroid abuse (13 years) (Madea & Grellner, 1998).
    3) Decreased testicular size is a common complaint among users (46% in one study) and a common finding in chronic users at autopsy (O'Sullivan et al, 2000; Thiblin et al, 2000).
    4) Females may experience masculinization with menstrual irregularities, clitoral enlargement, hirsutism, deepening of voice, oily skin, and breast atrophy, some of which may be permanent (Kam & Yarrow, 2005).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) PLATELET AGGREGATION
    1) WITH THERAPEUTIC USE
    a) CASE SERIES: In a study of 24 chronic steroid users, the following nonsignificant trends were found: increased platelet counts, increased platelet aggregation, and increased adenosine diphosphate-mediated aggregation (Ferenchick et al, 1992).
    1) Anabolic steroids are known to reduce the requirement for anticoagulants by 25%.
    B) ERYTHROCYTOSIS
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 44-year-old man sustained an acute inferior myocardial infarction associated with severe polycythemia secondary to testosterone abuse. His hemoglobin and hematocrit were 22 g/dl and 63%, respectively. He was treated with percutaneous transluminal coronary angioplasty and stent placement in the mid and distal right coronary arteries and was phlebotomized until his hematocrit reached 45%(Stergiopoulos et al, 2008).
    b) CASE REPORT: A 65-year-old man developed hypertension and polycythemia (hematocrit 55.5% to 58.5%) after topical testosterone to his scrotum daily for 5 years (estimated dose 10 milligrams testosterone/day). Polycythemia and hypertension resolved when testosterone was discontinued (Tangredi & Buxton, 2001).
    C) THROMBOEMBOLUS
    1) WITH POISONING/EXPOSURE
    a) It has been suggested that anabolic steroids are thrombogenic in humans by potentiating platelet aggregation. This has not been clearly established (Ferenchick, 1990).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) ACNE
    1) WITH POISONING/EXPOSURE
    a) PILOSEBACEOUS UNIT: Overactivity results in increased sebaceous material and follicular keratinization resulting in comedo formation from anabolic steroid use (Scott & Scott, 1989).
    b) CYSTIC ACNE: Rosacea, seborrheic dermatitis, sebaceous cysts, oily skin and hair, furunculosis, and folliculitis have occurred as a result of anabolic-androgens stimulating sebaceous glands (Scott & Scott, 1989).
    c) In one study 19 of 44 (43%) past and present users of androgenic steroids reported acne (O'Sullivan et al, 2000).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) DISORDER OF BONE DEVELOPMENT
    1) WITH THERAPEUTIC USE
    a) CHILDREN: Growing children may develop premature fusion of the epiphysis of long bones, leading to permanent short stature (Dyment et al, 1989; Scott & Scott, 1989; Lamb, 1984).
    B) DISORDER OF TENDON
    1) WITH THERAPEUTIC USE
    a) ADULT COLLAGEN: Anabolic steroid use in parallel with exercise may lead to dysplasia of collagen fibrils, decreased tendon strength, and increased likelihood of rupture under stress. Cases of unusual tendon rupture among steroid users, including 2 cases of triceps rupture, 1 of extensor pollicis longus rupture, and 1 of rectus femoris rupture have been reported (Laseter & Russell, 1991).
    C) GAS GANGRENE
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Approximately 36 hours after injecting anabolic steroids intramuscularly into the right thigh, a 36-year-old man presented to the emergency department complaining of progressive right thigh pain, swelling, fever and chills, and an inability to bear weight on his right leg. Physical examination of the right thigh revealed that it was swollen with a large area of ecchymosis at the injection site. Initial laboratory data revealed an elevated white blood cell count and creatine kinase concentration. Cultures were obtained that subsequently confirmed the preliminary diagnosis of clostridial myonecrosis. Despite emergent surgical debridement followed by daily debridements for 3 days, the patient's condition deteriorated with systemic complications, including hemolysis and acute anuric renal failure, necessitating initiation of hemodialysis. Five days postadmission, amputation of the right leg at the hip was performed, with subsequent improvement of kidney function and discontinuation of hemodialysis. Analysis of the vial containing the anabolic steroids determined that it had been contaminated with Clostridium perfringens (Driscoll et al, 2011).

Endocrine

    3.16.2) CLINICAL EFFECTS
    A) HORMONE LEVEL - FINDING
    1) WITH POISONING/EXPOSURE
    a) ABNORMAL HORMONAL PROFILES have been noted in men and women who use steroids chronically.
    1) WOMEN: A study of 9 steroid users compared to 7 controls demonstrated a significant decrease in sex hormone binding globulin and follicle stimulating hormone, and an increase in testosterone levels.
    a) SIGNS: Adverse effects noted in women athletes using steroids in cycles were lower voice, increased facial hair, enlarged clitoris, changes in libido, decreased breast size, changes or absence of menstrual function, increased aggressiveness, acne, increased body hair, loss of scalp hair, increased appetite, and decreased body fat (van Amsterdam et al, 2010; Strauss et al, 1985).
    2) MEN: Hormonal changes seen in male steroid abusers include decreased spermatogenesis, luteinizing hormone, follicle-stimulating hormone, and testosterone concentrations; and, in the case of testosterone or estrogen abuse, an increased growth hormone secretion (Alen & Rahkila, 1988).
    a) CASE SERIES: Four cases of reported gynecomastia among adult male bodybuilders taking multiple anabolic steroids. These men tried self-treatment with drugs such as tamoxifen; gynecomastia usually resolves, sometimes with residual tissue, after steroid use is stopped. One case self-treated with human chorionic gonadotropin and worsened his condition; he required mastectomy months later to remove the tissue(Friedl & Yesalis, 1989).
    B) HYPOGLYCEMIA
    1) WITH POISONING/EXPOSURE
    a) DIABETES: Anabolic steroids may decrease blood glucose in some diabetic patients. They inhibit the metabolism of oral hypoglycemic agents (Hansten, 1979).
    C) ATROPHY OF TESTIS
    1) WITH POISONING/EXPOSURE
    a) Decreased testicular size is a common complaint among users (46% in one study) and a common finding in chronic users at autopsy (O'Sullivan et al, 2000; Thiblin et al, 2000).
    D) GYNECOMASTIA
    1) WITH POISONING/EXPOSURE
    a) Gynecomastia is common among chronic users. It is estimated that gynecomastia develops in 10% to 34% of men abusing anabolic steroids (van Amsterdam et al, 2010).(O'Sullivan et al, 2000; Thiblin et al, 2000).
    E) ADRENAL ATROPHY
    1) WITH POISONING/EXPOSURE
    a) Adrenal atrophy is a common autopsy finding in chronic users (Thiblin et al, 2000).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) AIDS
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 26-year-old bodybuilder was infected with the acquired immunodeficiency syndrome virus after sharing an unsterilized needle with an HIV positive friend while self-administering injectable anabolic steroids (Scott & Scott, 1989a).

Reproductive

    3.20.1) SUMMARY
    A) Methandrostenolone has been shown to inhibit placental glucose-6-phosphatase in humans.
    B) Administration of anabolic steroids during gestation may result in masculinization of the urogenital sinus and clitoral hypertrophy. Premature bone maturation and decreased birthweight have been reported. Testosterone is contraindicated in women who are pregnant or who may become pregnant while taking the medication. Due to the potential for serious adverse effects to the infant from exposure to testosterone, breastfeeding is contraindicated.
    C) Danazol, esterified estrogens/methylTESTOSTERone, and testosterone are classified as FDA pregnancy category X .
    3.20.2) TERATOGENICITY
    A) ENZYME ABNORMALITY
    1) Methandrostenolone has been shown to inhibit placental glucose-6-phosphatase in humans (Holmberg, 1979).
    B) VIRILISM
    1) Testosterone is teratogenic and can cause fetal harm when given to a pregnant woman (Prod Info Natesto nasal gel, 2014; Prod Info AndroGel(R) 1.62% topical gel, 2011). Exposure of a female fetus to testosterone may result in varying degrees of virilization (Prod Info Natesto nasal gel, 2014; Prod Info AXIRON(R) topical solution, 2010).
    2) Administration of anabolic steroids during gestation may result in masculinization of the urogenital sinus and clitoral hypertrophy. Premature bone maturation and decreased birthweight have been reported (Tuchmann-Duplessis, 1975).
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) Danazol, esterified estrogens/methylTESTOSTERone, and testosterone are classified as FDA pregnancy category X (Prod Info Natesto nasal gel, 2014; Prod Info AndroGel(R) 1.62% topical gel, 2011; Prod Info AXIRON(R) topical solution, 2010; Prod Info ESTRATEST(R) oral tablets, ESTRATEST(R) HS half-strength oral tablets, 2005).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) Exposure to testosterone by a nursing infant may result in varying degrees of virilization and serious adverse events; therefore, testosterone is contraindicated in nursing women. The exact amount of testosterone found in human milk is not known (Prod Info Natesto nasal gel, 2014; Prod Info AndroGel(R) 1.62% topical gel, 2011; Prod Info AXIRON(R) topical solution, 2010).
    2) Testosterone is concentrated in breast tissue of women with breast cancer (Hill et al, 1983).

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) Fatal and benign hepatomas, adenocarcinoma of the prostate and sigmoid colon, Wilms tumor, hepatic angiosarcoma, and acute myeloid leukemia have been reported with anabolic steroids. Linkage between malignancies and abuse has not been clearly established.
    3.21.3) HUMAN STUDIES
    A) NEOPLASM
    1) Fatal and benign hepatomas, adenocarcinoma of the prostate and sigmoid colon, Wilms tumor, hepatic angiosarcoma, and acute myeloid leukemia have been reported in patients and athletes taking anabolic steroids. Linkage between malignancies and abuse of anabolic steroids has not been clearly established (Socas et al, 2005; Overly et al, 1984; Graham & Kennedy, 1990).
    3.21.4) ANIMAL STUDIES
    A) CERVICAL UTERINE TUMORS
    1) Testosterone implants induced cervical uterine tumors in mice, including some cases of metastases (Prod Info Natesto nasal gel, 2014; Prod Info AVEED(TM) intramuscular injection solution, 2014).
    B) HEPATOMA
    1) Testosterone subQ injections may cause increased susceptibility to hepatoma in some strains of female mice (Prod Info Natesto nasal gel, 2014; Prod Info AVEED(TM) intramuscular injection solution, 2014).
    C) LIVER CARCINOMA
    1) Testosterone increases tumor numbers and decreases degree of differentiation of chemically-induced liver carcinomas in rats (Prod Info Natesto nasal gel, 2014; Prod Info AVEED(TM) intramuscular injection solution, 2014).

Genotoxicity

    A) There was no evidence of mutagenicity of testosterone according to the chromosomal aberration in vitro tests in human lymphocytes, and in the in vitro Ames and in vivo mouse micronucleus assays (Prod Info AVEED(TM) intramuscular injection solution, 2014; Prod Info AVEED(TM) intramuscular injection solution, 2014).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs, particularly blood pressure. Monitor ECG in patients with cardiac symptoms or severe hypertension.
    B) Monitor liver enzymes, serum electrolytes, blood glucose, hemoglobin and hematocrit.
    C) PEDIATRIC: Obtain long bone radiographs to document the premature closure of the epiphysis in cases where children/adolescents have chronically used anabolic steroids.
    D) Gas chromatography-mass spectrometry analysis for specific anabolic steroid detection/levels can be performed, but are not readily available and are not clinically useful.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Liver-specific isoenzymes (AST, ALT, alkaline phosphatase, lactate dehydrogenase) should be used to monitor liver function in patients chronically using anabolic steroids(Haupt & Rovere, 1984).
    2) Monitor cholesterol profile, and CPK.
    B) ENDOCRINE
    1) Serum luteinizing hormone and serum follicle-stimulating hormone may be monitored (Brower, 1992a). In addition, testosterone abuse may be detected by checking the ratio of testosterone to epitestosterone. If this ratio exceeds 6 to 1, it is an indication of exogenous testosterone use (Fretthold, 1991).
    C) HEMATOLOGIC
    1) Hemoglobin and hematocrit should be monitored as polycythemia may develop with chronic use.
    4.1.3) URINE
    A) URINARY LEVELS
    1) Urine tests are used to detect steroid use in athletes. Oral products can be detected for 2 to 14 days after the last use and injectables for up to a month (Lamb, 1984).
    2) Other sources have suggested that oral agents can be detected for approximately 1 month (Cowart, 1987) and nandrolone decanoate injections for an average of 6 to 8 months, up to 12 months (Pers Comm, 1987).
    4.1.4) OTHER
    A) OTHER
    1) OTHER
    a) Monitor ECG in patients with cardiac symptoms or severe hypertension.
    b) Consider semen analyses in patients with fertility issues related to anabolic steroid use.
    c) Obtain long bone radiographs to document the premature closure of the epiphysis in cases where children/adolescents have chronically used anabolic steroids.
    2) MONITORING
    a) Periodic sulfobromophthalein tests should be performed when anabolic steroids are administered. Steroids can suppress ACTH reserve and uptake of radioiodine in thyroid. It has been known to raise serum cholesterol levels and cause hypercalcemia (Hansten, 1979).

Methods

    A) CHROMATOGRAPHY
    1) Hatton & Catlin (1987) describe a gas chromatography/mass spectrometry method that is the state-of-the-art analytical procedure for urine analysis. It provides unequivocal, extremely sensitive identification (1-10 ng/mL) of the anabolic steroid and known metabolites with no false positives.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with severe adverse reactions (eg, strokes) should be admitted, and depending on the severity of their symptoms, may merit an ICU admission. Criteria for discharge include resolution or treatment of their symptoms.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) The appropriate consultant should be called as needed (eg, neurologist for strokes, etc.). Consult a medical toxicologist or Poison Center for assistance in managing patients with severe toxicity or in whom the diagnosis is unclear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with significant adverse effects should be sent to a healthcare facility for treatment of their symptoms and should not be sent home until the symptoms are treated or resolved.

Monitoring

    A) Monitor vital signs, particularly blood pressure. Monitor ECG in patients with cardiac symptoms or severe hypertension.
    B) Monitor liver enzymes, serum electrolytes, blood glucose, hemoglobin and hematocrit.
    C) PEDIATRIC: Obtain long bone radiographs to document the premature closure of the epiphysis in cases where children/adolescents have chronically used anabolic steroids.
    D) Gas chromatography-mass spectrometry analysis for specific anabolic steroid detection/levels can be performed, but are not readily available and are not clinically useful.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Toxicity has been reported only after chronic use. Gastrointestinal decontamination is generally not needed after acute ingestion unless another toxic co-ingestant is involved. As a group, they are primarily inactive orally because of extensive first pass hepatic metabolism.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Toxicity has been reported only after chronic use. Gastrointestinal decontamination is generally not needed after acute ingestion unless another toxic coingestant is involved.
    6.5.3) TREATMENT
    A) MONITORING OF PATIENT
    1) Monitor vital signs, particularly blood pressure. Monitor ECG in patients with cardiac symptoms or severe hypertension.
    2) Monitor liver enzymes, serum electrolytes, blood glucose, hemoglobin and hematocrit.
    3) PEDIATRIC: Obtain long bone radiographs to document the premature closure of the epiphysis when children/adolescents have chronically used anabolic steroids.
    4) Gas chromatography-mass spectrometry analysis for specific anabolic steroid detection/levels can be performed, but are not readily available and are not clinically useful.
    B) DRUG OVERDOSE
    1) Acute single overdose toxicity is unlikely. Toxicity is seen with chronic use of anabolic steroids.
    C) CHRONIC POISONING
    1) In chronic toxicity, discontinue medications.
    D) DRUG WITHDRAWAL
    1) Patients who chronically misuse anabolic steroids may experience a withdrawal reaction. Steroid withdrawal needs to be treated as other drug withdrawals, including detoxification, support in denial phase, short term rehabilitation/recovery therapy, and long-term aftercare recovery (Giannini et al, 1991).

Enhanced Elimination

    A) ENHANCED ELIMINATION PROCEDURES
    1) There is no role for dialysis, hemoperfusion, urinary alkalinization, or multiple dose charcoal for anabolic steroid overdose.

Range Of Toxicity

Summary

    A) TOXICITY: A toxic dose has not been established.
    B) THERAPEUTIC DOSE: ADULT: Varies with drug and indication. FLUOXYMESTERONE: 2.5 to 20 mg orally daily in androgen-deficient males. METHYLTESTOSTERONE: 10 to 50 mg orally daily in androgen-deficient males; 50 to 200 mg orally daily as palliative treatment in women with metastatic breast cancer. OXANDROLONE: 2.5 to 20 mg orally daily in 2 to 4 divided doses. TESTOSTERONE: Transdermal patch, 2 to 6 mg/day; Topical gel (1%), 5 to 10 g once daily; Topical gel (1.62%), 20.25 to 81 mg once daily; Nasal gel, 11 mg three times daily (MAX dose: 33 mg); IM (testosterone cypionate and enanthate), 50 to 400 mg IM every 2 to 4 weeks. PEDIATRIC: Varies with drug and indication. FLUOXYMESTERONE: 2.5 to 20 mg orally daily. METHYLTESTOSTERONE: 10 to 50 mg orally daily. OXANDROLONE: Less than or equal to 0.1 mg/kg total daily dose, may be repeated intermittently as indicated. TESTOSTERONE (transdermal): Safety and efficacy have not been established in pediatric patients. TESTOSTERONE CYPIONATE (12 years and older): 50 to 400 mg IM every 2 to 4 weeks. TESTOSTERONE ENANTHATE: 50 to 400 mg IM every 2 to 4 weeks.

Therapeutic Dose

    7.2.1) ADULT
    A) SPECIFIC SUBSTANCE
    1) Variable depending upon the particular drug and the indication:
    a) FLUOXYMESTERONE: 2.5 to 20 mg daily; doses up to 40 mg/day have been used in women with inoperable mammary cancer (Prod Info ANDROXY(TM) oral tablets, 2006).
    b) METHYLTESTOSTERONE: 10 to 50 mg orally daily in androgen-deficient males as replacement therapy; doses of 50 to 200 mg have been used in women as palliative treatment in women with metastatic breast cancer (Prod Info METHITEST(TM) oral tablets, 2010).
    c) OXANDROLONE: 2.5 to 20 mg orally daily given in 2 to 4 divided doses (Prod Info oxandrolone oral tablets, 2006a).
    d) TESTOSTERONE
    1) Androderm(R) 2-mg/day and 4-mg/day transdermal systems: The recommended initial dose is one 4-mg/day system (NOT two 2-mg/day systems) applied nightly for 24 hours. May increase to 6 mg/day or decrease to 2 mg/day based on serum testosterone concentrations (Prod Info ANDRODERM(R) transdermal patch, 2012).
    2) Androgel(R) 1% topical gel: The recommended initial dose is 5 g (4 pump actuations from the from the 75 g multi-dose pump delivering 50 mg or sufficient number of 2.5 g or 5 g packets to deliver the intended dose) applied topically once daily (preferably in the morning). May increase dose to 7.5 to 10 g (6 to 8 pump actuations from the 75 g multi-dose pump or sufficient number of 2.5 or 5 g packets to deliver the intended dose) (Prod Info AndroGel(R) topical gel, 2011).
    3) Androgel(R) 1.62% topical gel: The recommended initial dose is 40.5 mg (2 pump actuations or a single 40.5 mg packet) applied topically once daily in the morning. May titrate to a daily dose between 20.25 mg (1 pump actuation or a single 20.25 mg packet) to a maximum of 81 mg (4 pump actuations or two 40.5 mg packets) based on pre-dose morning serum testosterone concentration drawn approximately 14 days and 28 days after starting treatment or following dose adjustment (Prod Info AndroGel(R) topical gel, 2012).
    4) Axiron(R) topical solution: The recommended initial dose is 60 mg (1 pump actuation of 30 mg to each axilla) applied topically once daily at the same time each morning. May decrease or increase dose by 30-mg increments (eg, from 60 mg to 30 mg or from 60 mg to 90 mg or 90 mg to 120 mg) based on serum testosterone concentration from a single blood draw 2 to 8 hours after application and at least 14 days after starting treatment or following dose adjustment (Prod Info AXIRON(R) topical solution, 2010).
    5) Fortesta(TM) topical gel: The recommended initial dose is 40 mg (4 pump actuations) applied topically once daily in the morning. Titrate dose to a minimum of 10 mg (1 pump actuation) or to a maximum of 70 mg (7 pump actuations) based on serum testosterone concentrations (drawn 2 hours after application) at approximately 14 days and 35 days after treatment initiation or following dose adjustments (Prod Info FORTESTA(TM) topical gel, 2010).
    6) Natesto(R) nasal gel: The recommended dose is 11 mg (2 pumps; 1 per nostril) administered 3 times daily (6 to 8 hours apart). MAX dose: 33 mg (Prod Info Natesto nasal gel, 2014)
    7) Testim(R) topical gel: The recommended initial dose is 5 g (contains 50 mg testosterone) applied topically once daily (preferably in the morning). May increase dose to 10 g daily after 2 weeks (Prod Info Testim(R) topical gel, 2011).
    e) TESTOSTERONE CYPIONATE
    1) 50 to 400 mg IM every 2 to 4 weeks (Prod Info testosterone cypionate intramuscular injection, 2012).
    f) TESTOSTERONE ENANTHATE
    1) MALE HYPOGONADISM: 50 to 400 mg IM every 2 to 4 weeks (Prod Info Delatestryl(R) intramuscular injection, 2014).
    2) DELAYED PUBERTY IN MALES: 50 to 200 mg IM every 2 to 4 weeks for 4 to 6 months (Prod Info Delatestryl(R) intramuscular injection, 2014).
    3) METASTATIC BREAST CANCER IN WOMEN, PALLIATIVE THERAPY: 200 to 400 mg IM every 2 to 4 weeks (Prod Info Delatestryl(R) intramuscular injection, 2014).
    g) TESTOSTERONE UNDECANOATE
    1) The recommended initial dose for primary hypogonadism in men is 750 mg (3 mL) IM, followed by 750 mg IM 4 weeks later, and 750 mg IM every 10 weeks thereafter (Prod Info AVEED(TM) intramuscular injection solution, 2014).
    B) ROUTE OF ADMINISTRATION
    1) "Stacking," a term used by body builders and athletes, refers to the concomitant use of two or more anabolic steroids at high doses (Kibble & Ross, 1987).
    2) "Cycling" refers to the drug-free periods between anabolic steroid regimens that are used to aid in preparation for an upcoming event (Kibble & Ross, 1987).
    3) Athletes individualize the dosing combinations of anabolic steroids to optimize steroid effect in anticipation that the athlete's performance will peak at contest time (Kibble & Ross, 1987).
    7.2.2) PEDIATRIC
    A) SUMMARY
    1) WARNING: Children and adolescents using anabolic steroids may never achieve full growth potential because of premature closure of the epiphysis of the long bones (Scott & Scott, 1989; Lamb, 1984).
    2) INDICATIONS: The accepted usage of anabolic steroid therapy in pediatrics are initiation of delayed puberty; growth promotion; treatment of micropenis; treatment of hypogonadism (Moore, 1988).
    B) SPECIFIC SUBSTANCE
    1) Androgen therapy should be used cautiously in pediatric patients with awareness of the potential for adverse effects on skeletal maturation.
    2) FLUOXYMESTERONE: 2.5 to 20 mg orally daily, depending on indication (Prod Info ANDROXY(TM) oral tablets, 2006).
    3) METHYLTESTOSTERONE: 10 to 50 mg orally daily (Prod Info METHITEST(TM) oral tablets, 2010).
    4) NANDROLONE DECANOATE: In children 2 to 13 years of age, the dose of nandrolone decanoate is 25 to 50 mg every 3 to 4 weeks (Prod Info Deca-Durabolin(R), nandrolone decanoate, 2001).
    5) OXANDROLONE: Less than or equal to 0.1 mg/kg total daily dose, may be repeated intermittently as indicated (Prod Info oxandrolone oral tablets, 2006a).
    6) TESTOSTERONE: Safety and efficacy have not been established in males less than 18 years of age (Prod Info Natesto nasal gel, 2014; Prod Info AVEED(TM) intramuscular injection solution, 2014; Prod Info ANDRODERM(R) transdermal patch, 2012).
    7) TESTOSTERONE CYPIONATE
    a) 12 YEARS AND OLDER: 50 to 400 mg IM every 2 to 4 weeks (Prod Info testosterone cypionate intramuscular injection, 2012).
    b) 11 YEARS AND YOUNGER: Safety and efficacy have not been established in pediatric patients less than 12-years-old (Prod Info testosterone cypionate intramuscular injection, 2012).
    8) TESTOSTERONE ENANTHATE
    a) MALE HYPOGONADISM: 50 to 400 mg IM every 2 to 4 weeks (Prod Info Delatestryl(R) intramuscular injection, 2014).
    b) DELAYED PUBERTY IN MALES: 50 to 200 mg IM every 2 to 4 weeks for 4 to 6 months (Prod Info Delatestryl(R) intramuscular injection, 2014).
    9) TESTOSTERONE UNDECANOATE: Safety and efficacy in pediatric patients less than 18-years-old have not been established (Prod Info AVEED(TM) intramuscular injection solution, 2014).

Maximum Tolerated Exposure

    A) SUMMARY
    1) MENSTRUAL IRREGULARITIES: Amenorrhea, hirsutism on the face and body, scalp alopecia, lowering of the voice, clitoral hypertrophy, and decreased breast size occur in females using anabolic-androgenic steroids. The effects are usually permanent and can appear after only one cycle of steroid use (Scott & Scott, 1989).
    2) ADOLESCENTS: Using anabolic steroids may never achieve full growth potential because of premature closure of the epiphysis of the long bones (Scott & Scott, 1989).

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Anabolic steroids cause a retention of nitrogen which may result in weight gain and a feeling of well-being. There is also retention of potassium, sodium, phosphorus and chloride associated with a gain in weight, which could be accounted for by the water held in association with the retained salts and protein.
    B) Anabolic steroids are thought to promote the improved use of proteins by contributing to the reversal of catabolic processes. Increased protein synthesis has been noted in skeletal muscle cells (Kibble & Ross, 1987).

Toxicologic Mechanism

    A) Reactive metabolic intermediates of misused anabolic steroids may be measured while they are covalently bound to hemoglobin and blood proteins. These compounds may be more responsible for toxicity and may also be more useful for measurement (Metzler, 1989).
    B) CARDIOVASCULAR TOXICITY - There are 4 proposed mechanisms of anabolic steroid-induced cardiovascular toxicity: atherogenic, thrombotic, vasospastic, and direct myocardial injury (Dhar et al, 2005).
    1) Anabolic steroid use is believed to promote the development of atherogenesis by increasing hepatic triglyceride lipase activity, which contributes to the catabolism of very low-density lipoproteins to low-density lipoproteins, and also to the catabolism of high-density lipoproteins.
    2) Anabolic steroids may cause hypercoagulability which in turn promotes platelet aggregation and intracoronary thrombus formation.
    3) Coronary vessel reactivity is the third proposed mechanism of anabolic steroid-induced cardiovascular toxicity. Anabolic steroids contribute to endothelial-dependent vascular dysfunction by inhibiting guanylyl transferase and decreasing the production of cyclic guanosine monophosphate.
    4) Direct myocardial cell injury, as the fourth proposed mechanism, may occur with anabolic steroid use due to disruption of myocardial mitochondria and induction of intrafibrillar collagen dysplasia. This may lead to fibrosis and an increased risk for ventricular dysrhythmias.

Physicochemical

Physical Characteristics

    A) FLUOXYMESTERONE is a white or practically white, odorless, crystalline powder; melting at about 240 degrees C with some decomposition; practically insoluble in water, sparingly soluble in alcohol, and slightly soluble in chloroform (Prod Info ANDROXY(TM) oral tablets, 2006).
    B) METHYLTESTOSTERONE is a white to creamy white, odorless, slightly hygroscopic powder; practically insoluble in water; soluble in alcohol and other organic solvents (Prod Info METHITEST(TM) oral tablets, 2010).
    C) NANDROLONE DECANOATE is a fine, white to creamy white, crystalline powder; odorless or may have slight odor; soluble in chloroform, in alcohol, in acetone, and in vegetable oils; practically insoluble in water (Prod Info nandrolone decanoate intramuscular oil, 2000).
    D) OXANDROLONE is a white, odorless crystalline powder; solubility is 1 in 5200 of water, 1 in 57 of alcohol, 1 in 69 of acetone, 1 in less than 5 of chloroform, and 1 in 860 of ether (Sweetman, 2004).
    E) TESTOSTERONE is a white to practically white crystalline powder (Prod Info AndroGel(R) 1% topical gel, 2013).
    F) TESTOSTERONE CYPIONATE is a white or creamy white crystalline powder; odorless or nearly so; stable in air; insoluble in water; freely soluble in alcohol, chloroform, dioxane, and ether; and soluble in vegetable oils (Prod Info testosterone cypionate intramuscular injection, 2012).
    G) TESTOSTERONE ENANTHATE IM injection is a colorless to pale yellow solution (Prod Info DELATESTRYL(R) intramuscular injection, 2011).
    H) TESTOSTERONE UNDECANOATE is a white to off-white crystalline substance; IM injection is a clear, yellowish, oily solution (Prod Info AVEED(TM) intramuscular injection solution, 2014).

Molecular Weight

    A) FLUOXYMESTERONE: 336.45 (Prod Info ANDROXY(TM) oral tablets, 2006)
    B) METHYLTESTOSTERONE: 302.46 (Prod Info METHITEST(TM) oral tablets, 2010)
    C) NANDROLONE DECANOATE: 428.7 (Sweetman, 2004)
    D) OXANDROLONE: 306.4 (Prod Info oxandrolone oral tablets, 2006)
    E) TESTOSTERONE: 288.42 (Prod Info AndroGel(R) 1.62% topical gel, 2011)
    F) TESTOSTERONE CYPIONATE: 412.61 (Prod Info testosterone cypionate intramuscular injection, 2012)
    G) TESTOSTERONE ENANTHATE: 400.6 (Prod Info DELATESTRYL(R) intramuscular injection, 2011)
    H) TESTOSTERONE UNDECANOATE: 456.7 (Prod Info AVEED(TM) intramuscular injection solution, 2014)

Animal Toxicology

Sources

    A) GENERAL
    1) BOLDENONE - Equipoise (R) is indicated as adjunctive treatment in horses debilitated through disease or overwork. Dosage for horses is 0.5 milligram/pound body weight intramuscularly once every three weeks. The main adverse effect is overaggressiveness and the drug should not be used on stallions, pregnant mares, or horses to be used as food. Supplied in 10 milliliter vials at 25 or 50 milligrams/milliliter or 50 milliliter vials at 50 milligrams/milliliter (Prod Info Equipoise(R), boldenone undecylenate, 1988).
    2) MIBOLERONE - Cheque (R) drops are indicated for canine estrus prevention in adult females. Female dogs over 7 months of age may be dosed for up to 24 months. Dosage: 0.3 milliliter for 1 to 25 pounds body weight; 0.6 milliliter for 25 to 50 pounds body weight; 1.2 milliliter for 51 to 100 pounds body weight; and 1.8 milliliter for adult German Shepherd dogs of all weights. This product should not be used in Bedlington Terriers, pregnant animals, or animals with a prior history of renal or hepatic disease. Supplied in 55 milliliter bottles of drops containing mibolerone 100 micrograms/milliliter and propylene glycol (Prod Info mibolerone, 1988).
    3) STANOZOLOL - Winstrol (R) is indicated to improve appetite and vitality in debilitated dogs, cats, and horses. Oral dosage for dogs and cats: 0.5 to one tablet twice daily for cats and small dogs, and 1 to 2 tablets twice daily for large dogs. Injectable dosage for dogs and cats: 25 milligrams for cats and small dogs and 50 milligrams for large dogs intramuscularly. Dosage for horses (injectable): 25 milligrams per 100 pounds body weight intramuscularly. This drug should not be administered to animals used for food, pregnant animals, and stallions. Supplied in two forms: injectable - vials of 10 and 30 milliliters at 50 milligrams/milliliter; and tablets - bottles of 50 and 500 scored, pink tablets containing 2 milligrams stanozolol and bottles of 50 and 250 beige chewable tablets containing 2 milligrams (Prod Info stanozolol, 1988).
    4) TESTOSTERONE PROPIONATE - HEIFER-oid (TM) implants are used in non-breeding feedlot cattle to improve rate of weight gain. Each dose unit contains 8 implant pellets, and each pellet contains 200 milligrams testosterone propionate and 20 milligrams estradiol benzoate. The implants are placed in the outer skin of the ear and no withholding period before slaughter is required. Adverse effects include masculine behavior, vaginal and rectal prolapse, and ventral edema. This product is NOT included under Schedule III of the Controlled Substances Act (Prod Info testosterone propionate, 1988).
    5) TRENBOLONE ACETATE - Finaplix(R)-S is an implant unit consisting of 7 small yellow pellets. Each pellet contains 20 milligrams trenbolone acetate and the whole implant unit is embedded in the outer skin of the ear. The product is used in feedlot steers to improve feed efficiency and rate of gain. The product is not for use in dairy or breeding animals. This product is NOT included under Schedule III of the Controlled Substances Act (Prod Info trenbolone acetate, 1988).

References

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    62) Product Information: ANDRODERM(R) transdermal patch, testosterone transdermal patch. Watson Pharma, Inc. (per FDA), Parsippany, NJ, 2012.
    63) Product Information: ANDROXY(TM) oral tablets, fluoxymesterone oral tablets. Upsher-Smith Laboratories,Inc, Minneapolis, MN, 2006.
    64) Product Information: AVEED(TM) intramuscular injection solution, testosterone undecanoate intramuscular injection solution. Endo Pharmaceuticals Solutions Inc. (per FDA), Malvern, PA, 2014.
    65) Product Information: AXIRON(R) topical solution, testosterone topical solution. Lilly USA, Indianapolis, IN, 2010.
    66) Product Information: AndroGel(R) 1% topical gel, testosterone 1% topical gel. AbbVie Inc. (per FDA), North Chicago, IL, 2013.
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    68) Product Information: AndroGel(R) topical gel, testosterone 1% topical gel. Abbott Laboratories (per FDA), Abbott Park, IL, 2011.
    69) Product Information: AndroGel(R) topical gel, testosterone 1.62% topical gel. Abbott Laboratories (per Manufacturer), North Chicago, IL, 2012.
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    71) Product Information: Deca-Durabolin(R), nandrolone decanoate. Organon Inc, West Orange, NJ, 2001.
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