Anabolic steroid use imbalance HDL and LDL cholesterol levels
Feb 19, 2006, 17:34, Reviewed by: Dr. Priya Saxena
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The researchers found that as expected, anabolic steroids lead to gains in both lean body mass and fat in men with HIV wasting.
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By University of California - San Francisco,
Anabolic steroid use causes decreased levels of HDL or "good" cholesterol, increased levels of LDL or "bad" cholesterol, and serious liver toxicity within 12 weeks, according to a study that measured the effects of anabolic steroids on men with HIV wasting disease.
The results have implications for athletes who take anabolic steroids to enhance performance, says principal investigator Carl Grunfeld, MD, PhD, chief of the metabolism and endocrine sections at the San Francisco VA Medical Center.
The researchers found that as expected, anabolic steroids lead to gains in both lean body mass and fat in men with HIV wasting.
"This is good news for people with devastating wasting illnesses, who suffer from the effects of loss of muscle mass and whose most immediate risk is that they will die of their disease," observes Grunfeld. "But for people who aren't this sick and who take anabolic steroids, there may be serious problems if these complications occur." Grunfeld, who is also a professor of medicine at the University of California, San Francisco, observes that "the biggest use of these steroids today is among body builders and athletes, who take these drugs to build muscle, but who could wind up with significantly damaged hearts and livers."
The randomized, double-blind trial among 262 HIV-positive men was the largest study of its type on men with HIV-associated weight loss, according to the study authors.
For the first 12 weeks of the trial, the men were randomly assigned to receive daily doses of either 20, 40, or 80 milligrams of the anabolic steroid oxandrolone or a placebo. They were allowed to receive open-label oxandrolone for the second 12-week period.
Grunfeld says the adverse effects of the steroids were clear-cut within the first 12 weeks. "HDL plummets. LDL goes up. This predisposes people to an increased risk of heart attack. Furthermore, we found grade III and grade IV liver toxicity in some men, which means a very significant risk of serious liver damage." The men's testosterone levels were also depressed. These effects were not seen in men taking placebo, according to Grunfeld.
The researchers observed that in men with the most wasting, the 20 milligram dose was more effective than higher doses in promoting weight gain. Subjects who weighed more and were healthier � and were therefore more like athletes who use the drugs, observes Grunfeld � required higher doses to gain weight. This is significant, he says, because it demonstrates in healthy people, "you need a higher dose to get a benefit � and the higher the dose, the more the toxicity."
Based on observed changes in HDL and LDL, Grunfeld estimates that heart attack risk would be increased 58 percent among men taking 20 milligrams of oxandrolone per day, two-fold with a 40 milligram daily dose, and three-fold with 80 milligrams. "Add smoking or hypertension, and the risk becomes really serious," he says.
The ability to promote gains in both muscle and fat makes these drugs unique among the medications used for HIV wasting disease, notes Grunfeld. He says that among patients with serious wasting illnesses, the benefits of immediate weight gain could still potentially outweigh the risks of longer-term heart and liver damage. For these patients, he says, it is important to have a store of fat as well as muscle mass, because "opportunistic infections burn up muscle if there's no fat there. The more fat you have, the less muscle you burn."
Nonetheless, he notes, "We would still stop the drug among anyone who has grade III or grade IV liver toxicity."
Grunfeld, who has no further plans to study steroids, says he would like to see the current study validated in two future studies by other investigators. The first would look exclusively at the 20 milligram dose in patients with significant wasting, because "it may work and have less toxicity." The second would investigate whether the same toxic effects occur in healthy individuals who take anabolic steroids. 
- The study is published in the March 2006 issue of the Journal of Acquired Immune Deficiency Syndromes. It is available online in the "Publish Ahead of Print" section of the journal.
www.ucsf.edu
Co-authors of the paper were Donald P. Kotler, MD, of St. Lukes Roosevelt Medical Center, New York; Adrian Dobs, MD, of Johns Hopkins School of Medicine, Baltimore; Marshal Glesby, MD, PhD, of the Community Research Initiative on AIDS, New York (at the time of the study); and Shalendar Bhasin, MD, of Charles Drew University of Medicine and Science, Los Angeles (at the time of the study).
The research was supported by a grant from Biotechnology General, Inc., now Savient Pharmaceuticals, Inc., makers of oxandrolone. In San Francisco, the grant was administered by the Northern California Institute for Research and Education.
UCSF is a leading university that consistently defines health care worldwide by conducting advanced biomedical research, educating graduate students in the life sciences, and providing complex patient care.
The mission of NCIRE is to improve the health and well-being of veterans and the general public by supporting a world-class biomedical research program conducted by the UCSF faculty at SFVAMC.
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