Continuing Education Activity

Anabolic steroids (also known as androgenic steroids) are synthetic derivatives of testosterone. Legal, as well as the illegal use of anabolic steroids, is gaining popularity. There are two types of anabolic steroids: 1) 17 alpha alkyl derivatives and 2) 17 beta ester derivatives. All anabolic steroids are DEA schedule III drugs. This activity will highlight the mechanism of action, adverse event profile, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions) pertinent to the interprofessional team members anabolic steroids appropriately for various indications.

Objectives:

• Identify the medically approved indications for anabolic steroid therapy.

• Describe the general mechanism of action of the anabolic steroid class of drugs.

• Summarize the potential adverse effects and indicate appropriate monitoring for adverse events when using anabolic steroids.

• Outline interprofessional team strategies for improving care coordination and communication to advance appropriate clinical outcomes with anabolic steroid therapy and improve outcomes, as well as measures to prevent misuse.

Indications

Anabolic steroids (also known as androgenic steroids) are synthetic derivatives of testosterone. Legal, as well as the illegal use of anabolic steroids, is gaining popularity. There are two types of anabolic steroids: 1) 17 alpha alkyl derivatives: e.g., oxandrolone, oxymetholone, and fluoxymesterone; and 2) 17 beta ester derivatives: e.g., testosterone cypionate, testosterone enanthate, testosterone heptylate, testosterone propionate, nandrolone decanoate, nandrolone phenpropionate, and dromostanolone. Nandrolone phenpropionate is a C18 androgenic anabolic steroid and was one of the first anabolic steroids to be used as a doping agent by professional athletes in the 1960s. It was banned from the Olympics by the IOC in 1974. All anabolic steroids are DEA schedule III drugs.[1][2][3]

FDA-approved indications for the use of anabolic steroids are primary hypogonadism, delayed puberty in boys (testosterone enanthate), hypogonadotropic hypogonadism (testosterone cypionate, enanthate, and undecanoate), gonadotropin and luteinizing hormone-releasing hormone deficiency, pituitary-hypothalamic axis dysfunction from various tumors, injury, and radiation. Other indications for the use of testosterone include primary testicular failure in patients with cryptorchidism, orchitis, testicular torsion, vanishing testis syndrome, previous history of orchiectomy, Klinefelter syndrome, chemotherapeutic agents, toxic damage from alcohol use, and heavy metals.

Non-FDA-approved indications of androgenic steroids include bone marrow stimulation in leukemia, aplastic anemia, kidney failure, growth failure, stimulation of appetite, and muscle mass in malignancy and acquired immunodeficiency syndrome. Anabolic steroid users are sometimes used by athletes at all levels in sports such as bodybuilding, weightlifting, baseball, football, cycling, wrestling, and many others to improve their performance.

Mechanism of Action

Endogenous androgen is responsible for the growth and development of the sex organs in men and maintaining secondary sex characteristics. Endogenous anabolic steroids such as testosterone and dihydrotestosterone and synthetic anabolic steroids mediate their effects by binding to and activating androgen receptors. In skeletal muscle, anabolic steroids regulate the transcription of target genes that control the accumulation of DNA in skeletal muscle required for muscle growth.[4][5][3]

Anabolic steroids also upregulate and increase the number of androgen receptors, thus enabling increased training intensity and indirectly contributing to increased muscle size and strength. They also have a stimulatory effect on the brain through their diverse effects on various central nervous system neurotransmitters, antagonism of glucocorticoids, and stimulation of the growth hormone-insulin-like growth factor-1 axis.

Nandrolone decanoate and nandrolone phenpropionate are associated with the increased ratio of anabolic activity versus androgenic activity. Nandrolone decanoate is a slow-acting anabolic steroid designed for the sole purpose of increasing muscle mass. It acts by promoting nitrogen retention in muscles, leading to an increase in muscle size, and providing joint pain relief by promoting collagen synthesis and enhancing bone mineralization. Nandrolone phenpropionate also causes an increase in muscle growth, stimulation of appetite, and an increase in the production of red blood cells.

Dromostanolone is a synthetic anabolic steroid with anti-estrogenic properties and is five times more potent than methyltestosterone, which is being used widely by bodybuilders to prepare for competition. It increases retention of nitrogen, phosphorus, and potassium, resulting in increased protein anabolism and a decrease in the catabolism of amino acids, leading to an increase in density and hardness of muscle.

Administration

Anabolic steroids administration can be via oral pills, injections, creams or topical gels, and skin patches.

1. Testosterone cypionate is given as 50 to 400 mg intramuscularly once to 4 times a month for primary hypogonadism and hypogonadotropic hypogonadism.
2. Testosterone undecanoate dosing starts as an initial dose of 750 mg, then 750 mg given four weeks after the first dose, and 750 mg subsequently, given at ten weeks intervals between each dose.
3. Testosterone gel is given as 11 mg 3 times daily, with a total dose of 33 mg daily.
4. Transdermal testosterone is applied as 50 mg applied once daily in the morning to the upper limb, shoulder, or abdomen with a maximum dose of 100 mg per day.
5. Another testosterone gel is given in the dose of 40 mg once a day every morning with a maximum dose of 70 milligrams per day.

Medications Not Approved by FDA for Medical Use

1. Nandrolone decanoate dosing is 100 mg per week for comfort and relief of joint pain and in the dose range of 200 mg to 400 mg per week to increase growth and performance. It is ideally used for about ten to twelve weeks to get the desired results in athletes, powerlifters, and bodybuilders.
2. Dromostanolone is available as 200 to 400 mg weekly, which bodybuilders use to enhance their athletic performance. Because of its short half-life, dromostanolone injections are administered every 3 to 4 days.

Adverse Effects

The following are a list of some of the adverse effects of anabolic steroids:

• Cardiovascular: Coronary heart disease, cardiomyopathy, and hypertension (3% or less)
• Endocrine and metabolic: Decreased HDL cholesterol (6% or less), hyperlipidemia (6% or less), hypokalemia, increased serum triglycerides thyroid-stimulating hormone level and plasma estradiol concentration, decreased libido (3% or less), gynecomastia (3% or less), hot flashes and weight gain
• Gastrointestinal: Gingivitis (9% or less), mouth irritation (9% or less), increased serum bilirubin, abnormal hepatic function tests, decreased appetite, dysgeusia, gastroesophageal reflux disease, and gastrointestinal hemorrhage.
• Genitourinary: Increase in prostate-specific antigen (topical 18% or less), benign prostatic hypertrophy (12%), testicular atrophy (6% or less), suppression of spermatogenesis, mastalgia, hypogonadism (following withdrawal), prostatitis, dysuria, hematuria, impotence, pelvic pain, urinary incontinence, urinary tract infection, testicular tenderness, ejaculatory disorder and erectile dysfunction (nandrolone)
• Hematologic and oncologic: Polycythemia (6%) and prostate carcinoma (less than 3%)
• Neuromuscular and skeletal: Myalgia (6% or less), premature epiphyseal closure (when taken before completion of puberty), limb pain, tendon rupture, abnormal bone growth, and hemarthrosis
• Neuropsychiatric: Emotional lability, major mood disorders, anosmia, headache, depression, nervousness, body pain, violence, insomnia, and aggressive behavior
• Dermatologic: Skin blister (12%), acne vulgaris (8% or less), crusted skin, nasal excoriation (6% or less), contact dermatitis, bulla, skin rash, and pruritus
• Renal: Increase in serum creatinine and frequency of urination
• Nandrolone causes hirsutism and deepening of voice in a woman with extended periods of use due to its androgenic properties.

Contraindications

Testosterone cypionate is contraindicated in the presence of severe renal, cardiac and hepatic disease, men with breast cancer and prostate cancer, venous thromboembolism, pregnant women, or women who may become pregnant breastfeeding women, hypersensitivity to any component of the formulation. The Endocrinology Society suggests that it may be judicious to avoid treatment with testosterone in men who have a history of myocardial infarction and stroke in the last six months.[6][7]

Monitoring

Before initiating treatment with testosterone, diagnosis of hypogonadism require confirmation by measuring early morning testosterone levels on two separate days. Lipid profile, hepatic function tests, hemoglobin, hematocrit, prostate-specific antigen, and prostate exam in patients older than 40 years of age are necessary before initiating treatment.

During treatment with anabolic steroids, clinicians should obtain the patient's lipid profile, hepatic function tests, hemoglobin, and hematocrit (at 3 to 6 months, then every year). Women treated with testosterone for breast cancer require monitoring for signs of virilization. Patients on testosterone should be monitored for their response to treatment and adverse effects three to six months after initiation of therapy and then every year, especially for cardiac adverse events.

Men greater than 40 years of age with baseline prostate-specific antigen (PSA) more than 0.6 ng/mL should have their PSA levels measured and a prostate examination at 3 to 6 months. Treatment should be withheld in men with a palpable prostate nodule or prostate-specific antigen more than 4 ng/mL and in patients at high risk of prostate malignancy with prostate-specific antigen more than 3 ng/mL.

Testosterone level should be measured midway between injections in testosterone enanthate and testosterone cypionate, and dose and frequency adjustments should be implemented to keep testosterone concentration between 400 ng/dL and 700 ng/dL (Endocrine Society 2010). Serum testosterone level should be measured two to eight hours after application and after fourteen days of starting the therapy or with dose titration in patients using a topical solution of testosterone.

Total serum testosterone should be measured periodically, starting from the first month after initiating therapy in patients using nasal testosterone gel, and treatment should terminate if total testosterone exceeds 1050 ng/dL. Serum testosterone level should be measured approximately 14 days after initiation of therapy, in the morning, before application of transdermal testosterone, at the end of the dosing interval in testosterone pellets, and 4 to 12 weeks after initiation of treatment and before the morning dose in patients using a buccal form of testosterone.[8][9]

Enhancing Healthcare Team Outcomes

There is no question that anabolic steroids do have a clinical role in patients with HIV, liver disease, renal failure, some malignancies, and in burn patients. But today, the problem with these agents is one of misuse. Despite legislation to limit the empirical prescription and dispensing of these agents, these medications continue to be misused by athletes. To prevent anabolic drug abuse, the role of the nurse and pharmacist is critical. Athletes need education about the potential harm from these drugs and that there are very sophisticated methods of detecting them in the blood and urine. Plus, athletes need to know that many anabolic steroids bought online are counterfeit and contain additives that may be toxic. The other problem is addiction to these agents and referral to a mental health counselor. Additionally, the user must understand that the psychoactive effects of anabolic steroids can be deadly, resulting in anger, suicidal thoughts, rage, and extreme violence. Abuse of anabolic steroids is a problem at all levels of schooling and includes both genders. The clinician, physician assistant, nurse, and pharmacist should encourage the cessation of these agents and refer the patient to the appropriate specialist for treatment.[10][11] [Level 3]

Proper therapeutic use and dealing with illegal misuse of anabolic steroids require an interprofessional team effort. In addressing illicit use, all members need to be aware of the signs of steroid misuse and be prepared to counsel as necessary to attempt to resolve the issue. In legitimate therapeutic use, the clinician will prescribe an agent based on clinical need, and the pharmacist can verify appropriate dosing and check for drug interactions. Nursing can provide counsel on administration along with the pharmacist and also monitor for adverse effects on follow-up visits; both pharmacists and nurses need an open communication channel to the prescriber in such instances. These actions show the potential effectiveness of an interprofessional team approach to anabolic steroid use or misuse. [Level 5]

Outcomes

When used appropriately, anabolic steroids can help with weight gain, but clinicians and the rest of the interprofessional team must monitor the patient for adverse effects. In general, when used for short periods when indicated, anabolic steroids can reverse cachexia in several disorders. At the same time, healthcare workers should be fully aware that these drugs suffer from misuse, and hence close monitoring is necessary.[12][13] [Level 3]