Anabolic Steroids


Article Author:
Kavitha Ganesan


Article Editor:
Patrick Zito


Editors In Chief:
Chaddie Doerr


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
2/2/2019 8:33:38 AM

Indications

Anabolic steroids (also known as androgenic steroids) are synthetic derivatives of testosterone. Legal, as well as 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 steroids 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 thereby indirectly contributing to an increase in 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 that was designed for the solitary purpose of increasing muscle mass. It acts by promoting nitrogen retention in muscles leading to an increase in muscle size and provide joint pain relief by promoting the synthesis of collagen and the enhancement of 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 an increase of protein anabolism and a decrease in the catabolism of amino acids, leading to an increase in density and hardness of muscle.

Administration

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

Adverse Effects

Following are 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 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 6 months.[6][7]

Monitoring

Prior to initiation of treatment with testosterone, diagnosis of hypogonadism should be confirmed by measuring early morning testosterone level 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 should be done prior to initiating treatment.

During treatment with anabolic steroids, lipid profile, hepatic function tests, hemoglobin, the hematocrit should be taken (at 3 to 6 months, then every year). Women treated with testosterone for breast cancer should be monitored for signs of virilization. Patients should be monitored for response to treatment with testosterone and also adverse effects three to six months after initiation of treatment 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 who are 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 done 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 the initiation of therapy in patients using nasal testosterone gel and should be stopped if total testosterone is greater than 1050 ng/dL. Serum testosterone level should be measured approximately 14 days after initiation of therapy, in the morning, prior to application of transdermal testosterone, at the end of the dosing interval in testosterone pellets, and 4 to 12 weeks after initiation of treatment and prior to morning dose in patients using a buccal form of testosterone.[8][9]

Enhancing Healthcare Team Outcomes

A multidisciplinary approach to anabolic steroids

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 abuse. Despite legislation to limit empirical prescription and dispensing of these agents, these medications continue to be abused by athletes. To prevent anabolic drug abuse, the role of the nurse and pharmacist are critical. Athletes have to be educated 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 also contain additives, that may be toxic. The other problem is one of addiction to these agents and referral to a mental health counselor. In addition, the user must be told 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 physician, physician assistant, nurse, and pharmacist should encourage cessation of these agents and refer the patient to the appropriate specialist for treatment.[10][11] (Level III)

Outcomes

When used appropriately, anabolic steroids can help with weight gain but one has to monitor the patient for adverse effects. In general, when used for short periods when indicated, the anabolic steroids can reverse the cachexia in a number of disorders. At the same time, healthcare workers should be fully aware that these drugs are abused and hence close monitoring is necessary.[12][13](Level III)


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Anabolic Steroids - Questions

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Which of the following medications can increase low-density lipoprotein (LDL) levels?



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Which of the following should be determined before initiating testosterone therapy for a patient with hypogonadism?



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Which one of the following is not a contraindication for testosterone cypionate?



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Which one of the following is not a mechanism of action of androgenic steroids?



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Which one of the following is not a FDA approved indication for the use of testosterone?



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Which one of the following is not a route of administration for testosterone?



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Anabolic Steroids - References

References

Lusetti M,Licata M,Silingardi E,Bonsignore A,Palmiere C, Appearance/Image- and Performance-Enhancing Drug Users: A Forensic Approach. The American journal of forensic medicine and pathology. 2018 Aug 27     [PubMed]
Jones IA,Togashi R,Hatch GFR 3rd,Weber AE,Vangsness CT Jr, Anabolic steroids and tendons: A review of their mechanical, structural, and biologic effects. Journal of orthopaedic research : official publication of the Orthopaedic Research Society. 2018 Jul 26     [PubMed]
Armstrong JM,Avant RA,Charchenko CM,Westerman ME,Ziegelmann MJ,Miest TS,Trost LW, Impact of anabolic androgenic steroids on sexual function. Translational andrology and urology. 2018 Jun     [PubMed]
Melo Junior AF,Dalpiaz PLM,Sousa GJ,Oliveira PWC,Birocale AM,Andrade TU,Abreu GR,Bissoli NS, Nandrolone alter left ventricular contractility and promotes remodelling involving calcium-handling proteins and renin-angiotensin system in male SHR. Life sciences. 2018 Sep 1     [PubMed]
Zhou S,Glowacki J, Dehydroepiandrosterone and Bone. Vitamins and hormones. 2018     [PubMed]
Garner O,Iardino A,Ramirez A,Yakoby M, Cardiomyopathy induced by anabolic-androgenic steroid abuse. BMJ case reports. 2018 Jul 23     [PubMed]
Costanzo PR,Pacenza NA,Aszpis SM,Suárez SM,Pragier UM,Usher JGS,Vásquez Cayoja M,Iturrieta S,Gottlieb SE,Rey RA,Knoblovits P, Clinical and Etiological Aspects of Gynecomastia in Adult Males: A Multicenter Study. BioMed research international. 2018     [PubMed]
Moretti S,Lega F,Rigoni L,Saluti G,Giusepponi D,Gioiello A,Manuali E,Rossi R,Galarini R, Multiclass screening method to detect more than fifty banned substances in bovine bile and urine. Analytica chimica acta. 2018 Nov 22     [PubMed]
Dahmani H,Louati K,Hajri A,Bahri S,Safta F, Development of an extraction method for anabolic androgenic steroids in dietary supplements and analysis by gas chromatography-mass spectrometry: Application for doping-control. Steroids. 2018 Oct     [PubMed]
Smit DL,de Ronde W, Outpatient clinic for users of anabolic androgenic steroids: an overview. The Netherlands journal of medicine. 2018 May     [PubMed]
Creagh S,Warden D,Latif MA,Paydar A, The New Classes of Synthetic Illicit Drugs Can Significantly Harm the Brain: A Neuro Imaging Perspective with Full Review of MRI Findings. Clinical radiology     [PubMed]
Andrews MA,Magee CD,Combest TM,Allard RJ,Douglas KM, Physical Effects of Anabolic-androgenic Steroids in Healthy Exercising Adults: A Systematic Review and Meta-analysis. Current sports medicine reports. 2018 Jul     [PubMed]
Elliott J,Kelly SE,Millar AC,Peterson J,Chen L,Johnston A,Kotb A,Skidmore B,Bai Z,Mamdani M,Wells GA, Testosterone therapy in hypogonadal men: a systematic review and network meta-analysis. BMJ open. 2017 Nov 16     [PubMed]

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