Use of the steroid oxandrolone is associated with significant gains in weight and body cell mass in HIV-positive men who had experienced HIV-related wasting, according to an American study. However, although the steroid increased muscle mass, it did not improve endurance and caused side-effects, including an increase in levels of ‘bad’ LDL cholesterol and elevations in liver enzymes.
Unintentional loss of just 3% of body weight has been associated with poorer survival in HIV-positive individuals. Although the use of antiretroviral therapy has led to a significant decrease in the prevalence of unintended weight loss, it is still common, even amongst people taking HIV treatment.
Diet and appetite stimulation can help increase weight in people affected by HIV-related wasting, but most of the gains of weight occur in the form of fat, and stores of body fat are not correlated with improved survival in HIV-positive individuals. Some small studies have shown that anabolic steroids can increase body weight and muscle mass in HIV-positive patients. To further investigate the benefits of treatment with anabolic steroid therapy, investigators designed a double blind placebo controlled trial in which men with HIV-associated wasting were randomised to receive a placebo or one of a 20mg, 40mg, or 80mg daily dose of the oral steroid oxandrolone. The investigators measured changes in the patients’ weight, body composition, endurance, and also conducted laboratory tests to assess the safety of steroid treatment. For the first twelve weeks, the men were provided with blinded treatment. At the end of this period, all the men were given the option of receiving an open-label 20mg daily dose of oxandrolone for a further twelve weeks.
The study was conducted between the autumn of 1996 and the summer of 1998. Treatment with antiretroviral drugs was not a prerequisite for entry to the study, but if an individual was taking anti-HIV treatment, they were required to have been taking a stable regimen for at least six weeks. The investigators do not state how many patients were taking anti-HIV therapy, nor do they analyse their results according to the use of antiretrovirals, making it difficult to determine the applicability of these results in patients experiencing HIV-related wasting despite antiretroviral therapy.
A total of 262 men were recruited to the study. CD4 cell count was comparable across the four arms of the study at approximately 250 cells/mm3, as was viral load at approximately 120,000 copies/ml.
Body weight increased significantly in all arms of the study, including the placebo arm during the double blind phase (p < 0.014). Body cell mass also increased in all arms of the study during this phase. However, when the investigators subjected their results to further analysis, they found that patients who took the 40mg dose of oxandrolone had significantly greater increases in body weight at weeks two, four, eight and twelve than those individuals who received a placebo (p < 0.004). Although patients receiving the 80mg dose of oxandrolone had significantly greater weight gains than patients on the placebo at weeks four and eight, this was not the case at weeks two or twelve.
In addition, the investigators found that patients treated with the 40mg (p = 0.0049) and 80mg (p = 0.0002) doses of oxandrolone experienced significant changes in body cell mass compared to patients who received the placebo.
Treatment with the steroid did not, however, lead to any improvement in endurance.
The investigators noted that levels of AST and ALT liver enzymes increased during the first four to eight weeks in patients receiving the 40mg and 80mg doses of oxandrolone. What’s more, they found a dose-related increase in the incidence of moderate-to-severe liver abnormalities in people taking the steroid. This was diagnosed by laboratory tests looking at AST, ALT, bilirubin, and uric acid levels. Analysis also showed that people treated with the 40mg and 80mg doses of the steroid were significantly more likely than those taking the placebo to experience an increase in their ‘bad’ LDL cholesterol (p < 0.017).
On completion of the twelve-week double-blind phase of the study, all the patients were offered the option of remaining on the study for a further twelve weeks and receiving an open label 20mg oxandrolone dose a day. By the end of this period, there were no differences in weight between patients and liver function ceased to be significantly different from baseline.
“Oxandrolone treatment was associated with significantly greater body weight gain above baseline than with placebo. A major portion of this weight gain occurred in the lean body compartment”, comment the investigators, who note that theirs was “the largest randomized placebo-controlled trial of an androgen in patients with HIV-associated weight loss.”
Although the investigators note that treatment with the steroid was generally “well tolerated” they note that over 5% of patients had moderate or severe increases in levels of liver enzymes and that “LDL levels decreased and HDL levels increased.”
They recommend “further studies…to determine the efficacy of oxandrolone in improving muscle strength, physical function, and health-related quality of life in HIV-infected patients with weight loss.
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