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

Background. Since its discovery in 1935, numerous derivatives of testostero ne have been synthesized, with the goals of prolonging its biological activ ity in vivo, producing orally active androgens, and developing products, co mmonly referred to as anabolic-androgenic steroids (AAS), that are more ana bolic and less androgenic than the parent molecule. Objective: This article reviews the structure, biotransformation, and mecha nism of action of testosterone and some of the most commonly used AAS. Clin ical 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 l ibraries of the University of Wisconsin Medical School and School of Pharma cy, the author's files, and searches of MEDLINE, Science Citation Index, Bi ological Abstracts, and Chemical Abstracts. Results: The myotrophic action of testosterone, and its derivatives and the ir stimulatory effects on the brain have led to widespread use of AAS by at hletes and "recreational" drug users. Consequently, all AAS were classified as class III controlled substances in 1991. Nonetheless, AAS have shown be nefit in a variety of human disorders, including HIV-related muscle wasting and other catabolic conditions such as chronic obstructive pulmonary disea se, severe burn injuries, and alcoholic hepatitis. Because of their diverse biological actions, AAS have been used to treat a variety of other conditi ons, including bone marrow failure syndromes, constitutional growth retarda tion in children, and hereditary angioedema. AAS therapy is associated with various side effects that are generally dose related; therefore, illicit u se of megadoses of AAS for the purpose of bodybuilding and enhancement of a thletic performance 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 alt eration of blood lipid levels and coagulation factors. Conclusions: To minimize or avoid serious toxicities with AAS therapy, clos e medical supervision and periodic monitoring are important, with dose adju stment as appropriate to achieve the minimum effective dose. Given the biol ogical effects and potential adverse effects of AAS, administration of thes e agents should be avoided in pregnant women, women with breast cancer or h ypercalcemia, men with carcinoma of the prostate or breast, and patients wi th nephrotic syndromes or significant liver dysfunction.