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A review of the chemistry, biological action, and clinical applications of anabolic-androgenic steroids

  • Nasrollah T. Shahidi
    Correspondence
    Address correspondence to: Nasrollah T. Shahidi, MD, Professor Emeritus, Department of Pediatric Hematology and Oncology, University of Wisconsin, 600 Highland Avenue, Madison, WI 53792-4672.
    Affiliations
    Department of Pediatric Hematology and Oncology, University of Wisconsin, Madison, Wisconsin U.S.A.
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      Abstract

      Background: Since its discovery in 1935, numerous derivatives of testosterone have been synthesized, with the goals of prolonging its biological activity in vivo, producing orally active androgens, and developing products, commonly referred to as anabolic-androgenic steroids (AAS), that are more anabolic and less androgenic than the parent molecule.
      Objective: This article reviews the structure, biotransformation, and mechanism of action of testosterone and some of the most commonly used AAS. Clinical applications of the AAS are discussed, and guidelines and therapeutic maneuvers for minimizing their side effects are outlined.
      Methods: Literature for inclusion in this review was identified using the libraries of the University of Wisconsin Medical School and School of Pharmacy, the author's files, and searches of MEDLINE, Science Citation Index, Biological Abstracts, and Chemical Abstracts.
      Results: The myotrophic action of testosterone and its derivatives and their stimulatory effects on the brain have led to widespread use of AAS by athletes and “recreational” drug users. Consequently, all AAS were classified as class III controlled substances in 1991. Nonetheless, AAS have shown benefit in a variety of human disorders, including HIV-related muscle wasting and other catabolic conditions such as chronic obstructive pulmonary disease, severe burn injuries, and alcoholic hepatitis. Because of their diverse biological actions, AAS have been used to treat a variety of other conditions, including bone marrow failure syndromes, constitutional growth retardation in children, and hereditary angioedema. AAS therapy is associated with various side effects that are generally dose related; therefore, illicit use of megadoses of AAS for the purpose of bodybuilding and enhancement of athletic performances can lead to serious and irreversible organ damage. The most common side effects of AAS are some degree of masculinization in women and children, behavioral changes (eg, aggression), hepatotoxicity, and alteration of blood lipid levels and coagulation factors.
      Conclusions: To minimize or avoid serious toxicities with AAS therapy, close medical supervision and periodic monitoring are important, with dose adjustment as appropriate to achieve the minimum effective dose. Given the biological effects and potential adverse effects of AAS, administration of these agents should be avoided in pregnant women, women with breast cancer or hypercalcemia, men with carcinoma of the prostate or breast, and patients with nephrotic syndromes or significant liver dysfunction.

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