Medical Indications of Anabolic Steroids

 Performance enhancing drugs (PED’s) have a wide range of uses in clinical medicine and especially Androgenic Anabolic Steroids (AAS) were initially recognized for their anabolic effects.  AAS therapy appears to have a favorable anabolic effect in patients with chronic diseases and muscle catabolism, such as cachexia associated with human immunodeficiency virus (HIV), cancer, burns, renal   failure. The effects on hematological parameters were recognized as early as 1942, before bone marrow transplantation and the use of synthetic erythropoietin became common, AAS were often used to treat various types of anemias associated with leukemia or kidney failure.

Moreover, AAS therapy does have several clinical uses other than androgen replacement. These compounds are used in the treatment of hereditary angioedema and in advanced breast cancer (as  anti-estrogen).[1]

AAS have beneficial effects on bone mineral density, through direct interaction with osteoblasts and by enhancing calcium reabsorption in renal tubules leading to calcium retention.

There are also reports of positive effects in fracture healing, in lubrication of synovial cavities, as well as on nitrogen balance in polytrauma patients. Some AAS can increase erythropoietin (EPO) production from the kidneys, iron absorption and also stimulate the production of  erythrocytes from bone marrow, improving erythropoiesis process. Other AAS are used to reverse wasting complications associated with HIV, by improving protein synthesisand restoration of lean body mass. It is important to note that, testosterone replacementtherapy (TRT) has beneficial effect in mood and cognitivefunctionin hypogonadal men and in patients with Alzheimer’s disease. [1, 2]

Furthermore recent studies have demonstrated that the normalization of low testosterone levels with TRT is associated with decreased incidence of metabolic syndrome and  type 2 diabetes mellitus, besides improving sexual function and the quality of life. [3]

The following drugs are classified into different groups and all have certain approved medical indications:

–  Testosterone: The major androgen in males and its purpose was mainly to treat hypogonadal males, suffering  from secondary hypogonadism. Testosterone therapy is also used in primary hypogonadism Kleinefelter syndrome (47XXY),delayed puberty in boys, 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, chemotherapeutic agents, toxic damage from alcohol use and heavy metals. [4]

–   Fluoxymesterone (Halotestin): A potent 17 alkylated oral AAS with high androgenic-anabolic activity, which is a testosterone derivative. Halotestin does not convert into estrogen (aromatization processing) and was used for the treatment of advanced breast cancer, even before Aromatase Inhibitors (AIs) were manufactured (late 90’s).

–   Oxymetholone (Anadrol): Another 17 alkylated oral AAS, which is a Dihydrotestosterone (DHT) derivative.   It was synthesized to treat aplastic anemia and was an alternative treatment (Anadrol 50) even before synthetic EPO was synthesized (late 90’s).

–   Stanozolol (Winstrol): A 17 alkylated AAS both in oral and injectable (suspension) forms. It is a DHT derivative, highly anabolic with weak androgenic properties. It was medically prescribed for patients suffering from hereditary angioedema. Other uses of Winstrol (Zambon/Desma) are muscle wasting/cachexia, anemia and osteoporosis.

–   Methandienone/Methandrostenolone (Dianabol): A  17 alkylated oral as well. It is a methyltestosterone derivative, which has high estrogenic activity (aromatase enzyme). It was the first AAS on the market, manufactured back in the mid 50’s by the American Dr. John Zigler (1954). The main medical indication of Dianabol was post traumatic syndrome and recovery after a surgical procedure, promoting anabolism, increasing appetite and glycogen retention restore.

–   Oxandrolone (Anavar): Another 17 alkylated AAS, a DHT derivative with high anabolic and low androgenic activity. Its medical use was against muscle wasting that occurs in acquired immunodeficiency syndrome (AIDS) patients. Another case where Anavar (Watson) was used was during burns in hospitalized patients. [5,6].Before GH was manufactures in 1985,oxandrolone was administrated in puberty girls for speeding up their delayed  height.

–   Methenolone (Primobolan): A DHT derivative AAS (injectable-enanthate/oral-acetate, no longer manufactured) with moderate anabolic and mild androgenic activity. Primobolan Depot (Bayer/Schering) is used against cachexia in old males and during muscle wasting that takes place in cancer patients.

–   Nandrolone (Deca-Durabolin): This injectable AAS is a 19nortestosterone derivative. Deca Durabolin (Organon)        is widely used in cases of bone fractures, or in menopausal women with low bone mineral density, against osteopenia/osteoporosis. Nandrolone Undecaonate can also treat cachexia in old males during andropause.[6]

–   Mesterolone (Proviron): An oral AAS, described as a synthetic form of Dihydroxytestosterone. Proviron’s (Bayer/Schering) medical use was to help older males to have a better sexual drive, to fight against dementia, depression and poor cognitive function.

–    Drostanolone (Masteron): An injectable AAS, described as another synthetic form of DHT. Masteron was initially used for advanced breast cancer in female patients, as an alternative treatment.

–    Tamoxifen Citrate (Nolvadex): An anti-estrogenic agent, belonging to the group of Selective estrogen receptor modulators (SERMs). Nolvadex (Astra Zeneca) is currently used for the treatment of both early and advanced estrogen receptor- positive breast cancer in pre- and post-menopausal women. Additionally, it is the most common hormone treatment for male breast cancer. It is used during a Post Cycle Therapy schedule, from bodybuilder trying to restore their Hypothalamic Pituitary Testicular Axis (HPTA).

–   Clomiphene Citrate (Clomid): Another SERM, which is medically used to treat infertility in women who do not ovulate. Clomifene has also been used with other assisted reproductive technology to increase success rates of these other modalities. It is combined with Tamoxifen citrate during PCT.

–   HCG: An LH analogue (LHRH), a peptide that resembles GnRH. It acts as a Luteinizing Hormone mimicker, thus boosting endogenous production of testosterone from Leydig cells of testicles.  Typical uses of HCG (Pregnyl/Organon) in men include hypogonadism and fertility treatment and young boys with un-descended testicles. Also, patients that undergo IVF, receive HCG to trigger the ovulation process.

–   Anastrozol (Arimidex/Astra Zeneca), Letrozol (Femara/Novartis), Exemestan (Aromasin/Pfizer): They all belong to the group of Aromatase Inhibitors, a class of drugs used in the treatment of breast cancer in postmenopausal women and gynecomastia in men. They may also be used for chemoprevention in high risk women.

–    Somatropin (hGH): Growth Hormone is used to treat growth failure in children with hormone deficiency, or in patients with short stature due to genetic syndromes. Somatropin (Humatrope/Lilly) is also used in adults to treat short bowel syndrome,Turner syndrome (45??) and  prevent severe muscle wasting in HIV+/AIDS patients.

–   Insulin: Is used to treat a number of diseases including diabetes mellitus type 1, diabetes mellitus type 2, gestational diabetes and complications of diabetes such as diabetic ketoacidosis and hyperosmolar hyperglycemic states. (Humulin-Humaloge/Lilly) comes in two different acting hormones (fast/slow action).

–   Metformin: This is a hypoglycemic compound that lowers insulin resistance to cells and improves insulin sensitivity in cells membrane receptors. Glucophage is medically prescribed for patients with Diabetes Mellitus type 2 (non insulin dependent), with glycemia and elevated Hg A1c.

–   Erythropoetin: This hormone is secreted by the kidney in response to cellular hypoxia; it stimulates red blood cell production (erythropoiesis) in the bone marrow. Recombinant human erythropoietin (rhEPO) is used in the treatment of anemia in chronic kidney disease, anemia in myelodysplasia and in anemia from cancer chemotherapy.

–   Ephedrnine HCL: This drug belongs to the class of adrenergic sympatheticomimetic CNS stimulants. It has the ability to promote peripheral vasoconstriction and improve symptoms of nasal congestionand allergic rhinitis.

–   Clenbuterol HCL: This compound is a sympathomimetic amine. It has the ability to promote bronchodilation, thus improving dramatically bronchial asthmatic crisis and upper respiratory airways obstruction (decongestant and bronchodilator).It is available either in oral form of tablet, or liquid form of syrup.

–   Thyroxine (T4), Triodothyronine (T3): Thyroid hormones are used to treat thyroid hormone deficiency, such as hypothyroidism. T4is metabolised more slowly than T3 and hence usually only needs once-daily administration. Levothyroxine Sodium is usually the first course of treatment tried.

–   Spironolactone, Furosemide: These are two diuretics that act differently. The former is potassium sparing, while the later is a non potassium sparing compound. Both (Aldactone/Pfizer & Lasix/Sanofi Aventis) are used for the treatment of edema, but also in some cases of hypertension (where there is also kidney or heart impairment).Furosemide is the first-line agent in most people with edema caused by congestive heart failure and is also used for liver cirrhosis, kidney impairment, nephrotic syndrome,

–   Aminoglutethimide: This is a cortisol blocker, which inhibits glucocorticosteroids production from the adrenal glands. As a medication (AG-Orimeten/Novartis) it has been used in the treatment of Cushing’s syndrome. AG is given in combination with hydrocortisone, prednisone, or an equivalent corticosteroid to prevent adrenal insufficiency.It was also an alternative medication for breast cancer,before the AIs were manufactured.

Besides the approved medical use of AAS against hypogonadism, recent clinical studies demonstrate a useful clinical role in patients with HIV, liver disease, renal failure, some malignancies and in burn patients. [7] AAS, growth hormone, insulin, diuretics, aromatase inhibitors, SERMs, CNS stimulants were all manufactured by chemists and physicians, in order to treat specific diseases in certain types of patients. But today the problem with these agents is one of abuse.Their use is against the laws of the International Olympic Committee. Moreover, their use should obey to the ethics of Hippocrates law. Therefore, the role of a Doctor of Medicine(MD) is critical for the safe use of these drugs.

References:

  1. Anabolic-Androgenic Steroid Therapy in the Treatment of Chronic Diseases.Shehzad BasariaJustin T. Wahlstrom, et al.   J Clin Endocrinol Metab. 2001 Nov;86(11):5108-17.
  2. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism.Katznelson L, Finkelstein JS, et al. J Clin Endocrinol Metab. 1996 Dec;81(12):4358-65.
  3. Cardiovascular benefits and risks of testosterone replacement therapy in older men with low testosterone.Chrysant SGChrysant GS. Hosp Pract 2018 Apr;46(2):47-55. doi: 10.1080/21548331.2018.1445405.
  4. Anabolic SteroidsKavitha Ganesan; Patrick M. Zito. https://www.ncbi.nlm.nih.gov/books/NBK482418/
  5. The anabolic androgenic steroid oxandrolone in the treatment of wasting and catabolic disorders: review of efficacy and safety. Orr RFiatarone Singh M. 2004;64(7):725-50.
  6. Novel Uses for the Anabolic Androgenic Steroids Nandrolone and Oxandrolone in the Management of Male Health.Wu CKovac JR. Curr Urol Rep.2016 Oct;17(10):72. doi: 10.1007/s11934-016-0629-8.
  7. Medical and Nonmedical Uses of Anabolic-Androgenic Steroids1990;264(22):2923-2927. doi:10.1001/jama.1990.03450220089029