Steroid Can Restore Body Tissue in HIV-Positive People

The oral anabolic steroid Oxandrolone is effective in restoring muscle and fat tissue that many HIV-positive people lose, according to a  new study.  HIV-related wasting is a complication in which people lose a significant percentage of their normal weight, leaving them at risk for secondary infections.

Carl Grunfeld of the University of California-San Francisco and colleagues gave 262 HIV-positive men who had experienced weight loss greater than or equal to 10% to 20% of their body mass index either oxandrolone - in doses of 20 mg, 40 mg or 80 mg - or a placebo daily for 12 weeks. The men who took the steroid in all dose levels had gained weight and muscle tissue, researchers found.

The steroid also produced side effects, including an increase in LDL cholesterol, which is considered unhealthy cholesterol, and a decrease in HDL cholesterol, which is considered healthy cholesterol, the study finds. Some of the men also showed signs of liver toxicity, according to the study. Current therapies for tissue loss, including nutritional supplements and a drug called megestrol acetate, mostly increase body fat, and growth hormone therapies, which also can treat tissue wasting, increase muscle mass but decrease fat stores.

Anabolic steroids like oxandrolone restore both tissue and fat, Grunfeld said, adding that the benefits must be weighed against the side effects. Grunfeld also said that although oxandrolone is not specifically approved for HIV-related wasting, physicians may prescribe it to treat the condition

Anabolic Steroids Help People with HIV Gain Weight

People with HIV who are treated with anabolic steroids to prevent AIDS wasting may realize modest gains in weight and muscle mass, a new review shows.

The review covered 13 studies of adults age 24 to 42 with HIV, 294 of whom received anabolic steroids for at least six weeks and 238 of whom received placebo. The average weight increase in those taking anabolic steroids was nearly three pounds.

“The magnitude of weight gain observed may be considered clinically relevant,” said lead author Karen Johns, a medical assessment officer from the agency Health Canada. “One hopes there would be greater weight gain with the long-term use of anabolic steroids; however, this has not been proven to date in clinical trials.”

AIDS wasting, which leads to significant weight loss in people with HIV, causes severe loss of weight and muscle and can lead to muscle weakness, organ failure and shortened lifespan. Researchers have long sought to reverse this common, destructive effect of HIV with mixed success.

The wasting stems from loss of the body’s ability to grow muscle and from low levels of testosterone.

Anabolic steroids are synthetic substances similar to the male sex hormone testosterone that promote growth of skeletal muscle and the development of male sexual characteristics.

Although most recently in the news for their misuse by professional athletes, anabolic steroids have legitimate medical application for men with low testosterone and people with certain types of anemia. Two anabolic steroids available in the United States, nandrolone decanoate and oxandrolone, have been used to help increase weight and muscle mass in small studies of people with wasting.

Conversely, anabolic steroid use has been associated with increased rates of HIV in those who share needles or use nonsterile needles when they inject steroids.

In the review studies, anabolic steroids were administered to patients either orally or by injection. The main side effects were mild and included abnormal liver function tests; acne; mild increase in body hair; breast tenderness; increased libido, aggressiveness and irritability; and mood swings — all common side effect of anabolic steroid use.

“The risks and side effects of taking anabolic steroids long-term are certainly of concern,” Johns said. “We were unable to assess these risks in our review due to the short duration of treatment in the studies.”

Wayne Dodge, M.D., the HIV/AIDS program director at the Group Health Cooperative in Seattle, suggests that clinicians should obtain blood testosterone levels, “if an HIV-infected individual has had significant weight loss, significant fatigue or muscle wasting, and particularly if associated with a significant decrease in libido and erections. If [testosterone] is in the low or low-normal range then a trial of [steroids] could be tried. The individual and the clinician should decide what result would constitute a successful trial: weight gain of 15 pounds, a 30 percent improvement in sense of well-being [or] a successful erection once a week.”

The reviews authors conclude that further studies are needed to determine if increase in weight leads to improved physical functioning and quality of life, and ultimately increased survival, as well as the potential for serious side effects, especially with prolonged use.

Use of Androgens in Patients Who Have HIV/AIDS

Of the 3 orally active anabolic steroids, oxandrolone has been studied in HIV-infected patients more extensively than has oxymetholone. Stanozolol is used for the treatment of hereditary angioedema and has not been used for its anabolic effect in this patient population to any great extent.

One of the earlier studies of oxandrolone in HIV-infected patients was begun before the introduction of the PIs. Sixty-three HIV-infected men with a loss of body weight greater than 10% were randomized to receive placebo; oxandrolone, 5 mg/d; or oxandrolone, 15 mg/d. The patients who received 15 mg/d of oxandrolone gained weight throughout the 16-week period, whereas those who received 5 mg/d of oxandrolone maintained their weight. In contrast, the patients who received placebo continued to lose weight.

In a follow-up study, which has not yet been published, patients were randomized to placebo or to 1 of 3 dosages of oxandrolone -- 20 mg/d, 40 mg/d, or 80 mg/d (C. Grunfeld, unpublished data, 1998). The patients in the group who received 40 mg/d had the most statistically significant weight gain. However, both the patients in this group and those who received 80 mg/d showed significant increases in serum levels of liver transaminases.

A study sought to determine whether a regimen of supraphysiologic doses of androgen (testosterone) plus an anabolic steroid (oxandrolone) would improve the LBM and strength gains achieved with progressive resistance exercise in HIV-infected men who had experienced weight loss.  A second objective of the study was to determine whether antiretroviral therapy with a PI prevented lean body anabolism.

All subjects in the study participated in supervised progressive resistance exercise for 8 weeks. At the same time, they received testosterone, 100 mg/wk, by intramuscular injection. Twenty-four eugonadal men were then randomized to either placebo or oxandrolone, 20 mg/d. Twenty-two patients completed the study. The results indicated that compared with patients who received placebo, those who received oxandrolone experienced improved nitrogen balance ( P = .05); increased LBM ( P = .005); and increased muscle strength, as judged by either maximum weight lifted ( P = .02 to .05) or dynamometry ( P = .01 to .05). The results were similar regardless of whether the patients were taking a PI. However, compared with placebo, oxandrolone was associated with a statistically significant decrease in blood levels of high-den-sity lipoprotein (HDL) cholesterol ( P < .001).

Because all patients in the study participated in progressive resistance training and received testosterone, only an additive effect of Oxandrolone versus placebo was being determined. Therefore, the study appears to be valid even though the number of patients enrolled was small. On the other hand, had the design of the study called for dividing the patients into multiple groups, so that not all patients received testosterone or participated in progressive resistance exercise, the number of patients required to reach statistical significance would have been much higher -- on the order of 350.

The conclusions that can be drawn from the study are that oxandrolone -- 20 mg/d, added to a program consisting of both progressive resistance exercise and physiologic doses of testosterone -- improved the anabolic and functional responses in patients who showed HIV-related weight loss.

Only one study of oxymetholone in HIV-infected patients has been reported. Patients were randomly assigned to receive either oxymetholone (14 patients) or oxymetholone plus ketotifen (16 patients). Ketotifen is an H 1-receptor antagonist (ie, antihista- mine) that has been shown to block tumor necrosis factor a. The patients receiving the medications under study were compared with 30 matched control patients who met the same inclusion criteria, such as advanced HIV infection and chronic cachexia.

At entry into the study, all patients had experienced significant weight loss (greater than 12 kg [26.4 lb]). The average weight gain by the patients who received oxymetholone was 8.2 kg (18 lb), a 14.5% increase over weight at entry ( P < .001). The average weight gain by the patients who received combination therapy was 6.1 kg (13.4 lb), a 10.9% increase over weight at entry ( P < .005). The untreated control patients lost an average of 1.8 kg (4 lb).

Both groups of treated patients showed improvement in the ability to perform activities of daily living (the Karnofsky Index) and in several quality-of-life variables.

Although this study was not a double-blind clinical trial, the investigators believed that the results suggested the need for a randomized, double-blind, placebo-controlled, multicenter trial.

Anabolic steroids for the treatment of weight loss in HIV-infected individuals

Anabolic steroids may be beneficial in the treatment of weight loss in HIV-infected individuals. Anabolic steroids include testosterone and its derivatives. One of the functions of testosterone is to help build muscle. Testosterone has been demonstrated to increase muscle mass and lean body mass in testosterone-deficient but otherwise healthy men. Individuals with HIV infection often lose weight and have low blood levels of testosterone; thus, the use of anabolic steroids in the treatment of weight loss in individuals with HIV infection may be beneficial.

The purpose of this review was to evaluate anabolic steroids as a means of treatment of weight loss in individuals with HIV infection. The review includes 13 randomized clinical trials in the primary analysis. The results suggested that anabolic steroids increased both lean body mass and body weight.

However, the results were not consistent among individual trials and the average increase was small and may not be clinically relevant. Furthermore, the results need to be interpreted with caution as this meta-analysis was limited due to small sample sizes; short duration of treatment and of follow-up; and heterogeneity of the study populations, the anabolic interventions, and concomitant therapies.