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Study Raises Doubts About Claims for 'Andro'

In the first human study of androstenedione since 1962, researchers from Iowa State University in Ames have found that the purported muscle-building supplement does not live up to advertising claims and may have adverse side effects. Though experts in the subject area generally welcome the study, one worries that misinterpretation of the study could cause physicians to lose credibility with patients.

'Andro' Can't Beat Placebo

The Iowa researchers measured the short-term effect of androstenedione on serum hormone levels, and also evaluated its muscle develpment effect on men who took the supplement during an 8-week resistance training program. The study (1) was supported by EAS, Inc, Golden, Colorado, an androstenedione manufacturer.

In the short-term arm of the study, 10 men were randomly assigned in double-blind fashion to take a single 100-mg dose of androstenedione or placebo. Blood samples were obtained before and every 30 minutes after ingestion for 6 hours.

Serum androstenedione peaked 90 to 270 minutes after ingestion, remaining above baseline until 270 to 360 minutes after ingestion. The single dose did not change serum concentrations of luteinizing hormone, follicle-stimulating hormone, or free or total testosterone.

In the resistance-training arm of the study, 20 previously untrained men between ages 19 and 29 were randomly assigned in double-blind fashion to receive 300 mg of androstenedione or placebo daily during weeks 1, 2, 4, 5, 7, and 8 of an 8-week training program. The cyclical schedule was used as recommended by the manufacturers to imitate the regimen used by many athletes. The dosage was the maximum typically recommended by manufacturers and the same dosage as was shown in a 1962 study (2) to increase serum testosterone levels in women. The resistance training program targeted all major muscle groups. Researchers assessed muscle strength, body composition, diet, blood chemistry, and muscle histochemistry.

In the androstenedione group, serum concentration of the supplement was 100% above baseline after 2 and 5 weeks of training and remained elevated after 8 weeks. Serum free testosterone was higher in the androstenedione group than in controls before supplementation began and did not change during training and supplementation. The two groups did not differ in serum total testosterone either before or during supplementation. Serum estradiol and estrone increased significantly in the androstenedione group, but estriol concentration did not change. The only blood chemistry finding was a 12% reduction in serum high-density lipoprotein cholesterol (HDL-C) concentration in the androstenedione group.

The researchers found no differences between the two groups in strength, muscle histochemistry, or body composition. Muscle strength and lean-body mass increased significantly and similarly in both groups, while fat mass decreased in both study groups.

Clinical Interpretations

The authors suggest that androstenedione does not augment size and strength gains from resistance training and that elevations in estrone and estradiol in the androstenedione group point to significant aromatization of the ingested supplement.

They also noted that the finding of significantly lowered HDL-C agrees with previous studies on anabolic steroids. They commented that though the mean HDL-C didn't drop to 35 mg/dL, the level considered to be a risk factor for cardiovascular disease, the decrease was clinically relevant. They also expressed concern about the potential adverse effects of increased hormone levels, including gynecomastia and cardiovascular disease in men (estrogen), breast cancer in women (estradiol), pancreatic cancer in men (estradiol and androstenedione), and prostate cancer (androstenedione).

Priscilla M. Clarkson, PhD, president-elect of the American College of Sports Medicine, says the study was well controlled and contains important clinical messages. "The long-term use of this product could have negative health consequences," says Clarkson, who is associate dean of the School of Public Health and Health Sciences and a professor in the Department of Exercise Science at the University of Massachusetts. "Taking more than the manufacturer-recommended amounts could be dangerous and not have the effect that weight lifters and bodybuilders are seeking."

Other researchers raise questions about the methodology of the study and about how the results may be perceived by athletes. Charles E. Yesalis III, MPH, ScD, in an editorial that accompanies the study (3), commented that the large strength gains noted in all of the untrained subjects could have masked any possible gains from androstenedione and that results in trained subjects could be different. Yesalis is a professor of health policy and administration and exercise and sports science at The Pennsylvania State University in University Park.

Yesalis also wrote that the dose used in the study (300 mg), though above some manufacturer-recommended doses, is low compared with the 500- to 1,200-mg doses promoted in advertisements for other androstenedione products. Yesalis said that studies are needed to evaluate the health implications of long-term high dosages and pressed for federal government removal of androstenedione and other "prohormones" from the market.

Gary A. Green, MD, clinical associate professor in the Department of Family Medicine at the University of California, Los Angeles (UCLA), says he's not convinced that androstenedione has little effect on testosterone levels, and adds that bioavailability studies are needed to track the supplement through the metabolic pathways. Work at the UCLA lab, he says, suggests that androstenedione is converted to testosterone very rapidly before it is metabolized into other substances such as estrogen and estradiol, suggesting that the testosterone increase is very transient.

Green says he is concerned about how the lay press has portrayed the study as the definitive word on androstenedione. "This is the first pilot study on andro, and there are going to be some problems and limitations. The scientific community understands that," says Green, who is a researcher at the Olympic Analytical Laboratory at UCLA and chairs the drug testing committee for the National Collegiate Athletic Association. But he worries that athletes who see themselves or their peers gaining strength while using andro may doubt the scientific community, including their physicians. He notes that preliminary studies on anabolic steroids also suggested that the drugs were similarly ineffective and involved untrained subjects.

Lisa Schnirring


  1. King DS, Sharp RL, Vukovich MD, et al: Effect of oral androstenedione on serum testosterone and adaptations to resistance training in young men: a randomized controlled trial. JAMA 1999;281(21):2020-2028
  2. Mahesh VB, Greenblatt RB: The in vivo conversion of dehydroepiandrosterone and androstenedione to testosterone in the human. Acta Endocrinol 1962;41:400-406
  3. Yesalis CE III: Medical, legal, and societal implications of androstenedione use. JAMA 1999;281(21):2043-2044

Washington Forums Address Women's Sports Medicine Issues

Two June meetings held to chart directions for research on women's sports injuries were capped by a Washington, DC, press briefing to generate federal support for research.

At the Capitol Hill briefing, held June 29 to coincide with the start of the Women's World Cup soccer tournament, researchers outlined areas for future study that had been identified 2 weeks earlier at a conference held in Hunt Valley, Maryland, and sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and the American Academy of Orthopaedic Surgeons (AAOS). (NIAMS is a branch of the National Institutes of Health.) "This [NIH] meeting was mostly motivated by the wonderful growth in women's sports and fitness," says Joan A. McGowan, PhD, chief of the musculoskeletal diseases branch of NIAMS. "This is the fact-finding that goes on in advance of NIH funding," she says. McGowan says the AAOS will publish a book containing the papers presented at the Hunt Valley meeting.

As outlined in a NIAMS press packet, researchers seek to determine to what degree sports injuries differ according to gender. Specific goals are to:

  • Define the epidemiology of acute and overuse injuries in females of all age-groups;
  • Determine the impact of exercise and sports participation on women's musculoskeletal health;
  • Identify injury mechanisms and risk factors;
  • Evaluate training, conditioning, coaching, and education interventions;
  • Identify and promote exercise for lifetime participation; and
  • Determine if exercise prevents non-sports-related musculoskeletal injuries.

In advance of the NIH meetings, about 20 experts on women's noncontact anterior cruciate ligament (ACL) injuries met in Hunt Valley to work toward a consensus on several risk-factor issues. Letha Y. Griffin, MD, PhD, who chaired the group, says the biggest news to come from that meeting was an agreement that neuromuscular differences are probably the biggest reason why noncontact ACL injuries are more common in women than in men. The group agreed that more research is needed to define the roles of anatomy, environment, and hormones in women's ACL injuries, says Griffin, an orthopedic surgeon and team physician at Georgia State University in Atlanta.

Griffin says agreement on the role of neuromuscular differences shifts attention to programs designed to prevent injuries, such as preseason neuromuscular conditioning and teaching women how to respond to high-risk situations. "We should at least adopt some of the prevention programs that seem to work," Griffin says. "We also need to verify that the programs are valid and identify what parts of the programs are most important."

Lisa Schnirring

Field Notes

GI Problems in Endurance Athletes
Most distance runners, cyclists, and triathletes have occasional gastrointestinal (GI) symptoms while training and competing, but the location of symptoms varies with the type of activity, says a research report in the June issue of The American Journal of Gastroenterology.

A mail questionnaire was sent to 199 runners (114 men and 85 women), 197 cyclists (98 men and 99 women), and 210 triathletes (110 men and 100 women), and 93%, 88%, and 71% of these respective groups responded.

Among runners, occasional or frequent lower-GI symptoms were more common than upper-GI symptoms (71% vs 36%), whereas cyclists reported having both upper- and lower-GI symptoms (67% and 64%). Triathletes experienced both upper (52%) and lower (45%) symptoms during cycling, but had more lower than upper symptoms while running (79% vs 54%).

Dead Snakes Can Still Bite
Rattlesnakes can be dangerous even after they have been decapitated, wrote Jeffrey R. Suchard, MD, and Frank LoVecchio, DO, in a letter published in the June 17 issue of The New England Journal of Medicine. Data collected at the Good Samaritan Regional Medical Center in Phoenix show that "imminently fatal injuries" do not prevent rattlesnakes from biting humans.

Of the 34 patients admitted to the Phoenix center for rattlesnake bites in a recent 11-month period, 5 were bitten by snakes that had been fatally injured and were presumed dead, Suchard and LoVecchio reported. One patient was bitten on the index finger after picking up a snake he had bludgeoned in the head and assumed was dead. Another was bitten after picking up a snake he had shot, then decapitated.