Is there a role for androgenic anabolic steroids in medical practice?

ANDROGENIC ANABOLIC STEROIDS (AASS) HAVE BEEN touted as either a poison or a panacea. Members of the lay community, particularly athletes, have long claimed that the anabolic steroids have muscle-building potential that results in improved physical functioning. The medical community has countered that these drugs are dangerous and are associated with multiple adverse effects. At long last, some quality clinical research is being done to determine whether AASs have any legitimate role in medical therapeutics and, if so, in which patient populations. Anabolic steroids have been used by the medical community in rare situations. For instance, in the 1960s before recombinant human growth hormone became available, oxandrolone was used to treat short stature in Turner syndrome. Most studies of boys and girls with short stature or delayed puberty showed growth acceleration but no increase in final height. Therefore, although recombinant human growth hormone is expensive and needs to be taken as a subcutaneous injection, it is unlikely that anabolic steroids will replace growth hormone in treating short stature. A more relevant question is whether AASs have a role in treating specific disease states and, if so, in whom and when. There is some suggestion that body composition affects health outcomes. For example, just as excessive abdominal obesity is a strong cardiovascular risk factor, loss of lean body mass also may have importance as a prognostic risk factor. Best studied in human immunodeficiency virus (HIV)– associated wasting syndromes, loss of lean body mass is a strong predictor of increased mortality. Several studies have shown that when hypogonadism occurs in conjunction with weight loss in patients with HIV infection, treatment with testosterone or oxandrolone results in increased lean body mass. Although it has not been definitively proved, maintaining or increasing lean body mass may be beneficial for long-term survival in HIV-infected individuals. Clinicians caring for cachectic patients will agree that it is important to maintain energy intake during illness, not just to maintain weight but to maintain lean muscle mass, although how lean body mass provides protection is not yet clear. It may be a direct effect whereby muscle mass improves the effectiveness of chemotherapy or antiviral agents; or it could be a surrogate marker for weight or other factors known to affect survival. In this issue of THE JOURNAL, Strawford et al show the importance of AASs in treating HIV-associated wasting and Johansen et al report on the benefits of using AASs in patients with chronic renal failure. These studies join others that have shown the merits of AASs in chronically ill patients who have lost body mass, including patients with cirrhosis, pulmonary disease, and burns. Strawford et al recruited 24 eugonadal men with HIV infection who had lost a mean of 9% of their baseline weight. Volunteers whose therapy included a combination of exercise and testosterone were randomized to take either oxandrolone or placebo. The addition of oral oxandrolone, 20 mg/d, provided some additional benefit over exercise alone in increasing nitrogen retention, lean body mass, weight, and muscle strength. This is an intriguing study design because all participants had normal serum testosterone levels prior to randomization and all were administered low-dose testosterone to prevent the decline in this hormone that often occurs when AASs are used alone. However, it is not clear that the administration of “physiologic testosterone replacement” to both groups was necessary. Serum testosterone levels after treatment with only testosterone were not statistically significantly different from the pretreatment values, yet it did result in suppression of serum gonadotropin levels, suggesting supraphysiological androgen replacement. Therefore, the study may have compared 2 levels of AASs, rather than comparing oxandrolone with physiologic androgen concentrations. Johansen et al took a slightly different tack by enrolling malnourished men and women, not necessarily those who had lost weight, and randomized them to receive intramuscular nandrolone or placebo. Although the increase in weight was similar between groups, subjects treated with nandrolone had a significant increase in lean body mass and in serum creatinine levels. Functional status was improved as tested by walking and stair climbing. Such data are po-