Men who suffer from HIV-wasting syndrome can benefit significantly from a combination of exercise and regular, moderate doses of male hormones, according to a new clinical study led by a University of California San Francisco researcher.
The study team found the combined therapy produced an increase in lean-body mass and muscle strength, regardless of whether a patient was undergoing treatment with HIV anti-retroviral drugs known as protease inhibitors.
"This is an important point because weight gain after initiation of protease inhibitor therapy usually takes place through the accumulation of body fat, but our goal in patients with HIV-related weight loss is to build-up the lean tissue," said lead study investigator Marc Hellerstein, MD, PhD, UCSF associate professor of medicine who treats patients at San Francisco General Hospital Medical Center.
The other key finding is that only a small amount of male hormones--or androgens--was necessary to produce positive results. "Much larger doses of androgens are often used by body-builders to develop muscular tissues, but such amounts have unproven long-term safety," said Hellerstein, who also is an associate professor of nutritional sciences at UC Berkeley.
Research results are reported in the current issue (April 14) of the Journal of the American Medical Association.
There were 22 study patients. All participants took part in a weight-lifting exercise regimen that was supervised by a trainer and received the male hormone, testosterone, by injection.
In addition, one group of 11 patients received oxandrolone, a synthetic hormonal agent belonging to the class of androgens called anabolic steroids. Another 11 patients received a placebo, an inactive substance used as a comparison.
The study was "double-blind," so during the course of the research neither patients nor research staff knew which product was being administered. Both placebo and oxandrolone were taken in tablet form.
Of the total study population, 13 patients were taking protease inhibitors as a treatment for HIV infection. They were represented evenly in both groups.
Study findings showed that both groups had increases in lean body mass, weight, and strength, but the gains were substantially greater in the oxandrolone-supplemented group. These results were the same whether or not patients were undergoing protease inhibitor therapy.
Previous research done elsewhere in healthy men had found that a very high dose of testosterone combined with exercise produced greater increases in lean tissue and in muscle strength than either treatment by itself. "These results presented our team with valuable data, but the long-term safety and behavior consequences of very high doses of testosterone are unknown, so we developed a protocol that would incorporate a lower dose of androgen therapy that included testosterone and an anabolic steroid," he said.
At the beginning of the UCSF study, participants ranged in age from 40-42 years and in weight from about 151-161 pounds. Other characteristics included HIV-positive status, normal testosterone levels, and an average weight loss of 8-9 percent during the previous two years but stable weight during the preceding three months.
Research findings from the oxandrolone and placebo groups, respectively, were: average weight gain, 14.7 pounds versus 9.3, and rate of lean body mass gain per week, 2.0 pounds versus 1.0. The oxandrolone group also showed an increase in muscle strength (chest, triceps, leg) over the placebo group by a measurement of .04 percent.
Patients in both groups showed a similar decrease in body fat and increase in bone mineral content.
While physical over-training may suppress immune function, the exercise program incorporated in the study showed "no evidence of worsening immunologic or virologic status," according to the researchers.
The study lasted eight weeks and was carried out in conjunction with the Western Human Nutrition Research Center in San Francisco, operated by the U.S. Department of Agriculture. Study subjects spent two 10-day periods as inpatients at the Center, where metabolic and other tests were conducted.
Study co-investigators are Alison Strawford, PhD, UC Berkeley and London School of Hygiene and Tropical Medicine; Elizabeth Parks, PhD, and Richard Neese, PhD, UC Berkeley; Mark Christiansen, MD, UCSF-affiliated San Francisco General Hospital Medical Center and UC Berkeley; Theresa Barbieri, Marta Van Loan, PhD, and Janet King, RD, PhD, U.S. Department of Agriculture; Norman Barton, MD, PhD, Bio-Technology General Corporation, Iselin, N.J.; and Don Catlin, MD, UCLA.
Placebo tablets and oxandrolone tablets were provided by Bio-Technology General Corporation.
The research was supported in part by grants from the National Institutes of Health, Bio-Technology General Corporation, and a sport consortium of the National Collegiate Athletic Association, United States Olympic Committee, and National Football League.
Journal
JAMA