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THE PHYSICIAN AND SPORTSMEDICINE - VOL 26 - NO. 5 - MAY 98


DHEA: Hype, hope not matched by facts

Food supplement makers and their allies have been promoting the hormone dehydroepiandrosterone (DHEA) as a virtual fountain of youth—the answer to everything from osteoporosis and diabetes to cancer and depression. DHEA's popular reputation, however, seems to bear little resemblance to the current scientific record.

The evidence for human benefits from DHEA is preliminary and inconclusive, and researchers who are studying the substance discourage its use because of adverse side effects and uncertainty about long-term risks.

What Is DHEA?

DHEA is secreted by the adrenal glands and is converted into testosterone and estrogen. DHEA levels are high at birth but plunge during childhood, rise sharply during puberty, and peak during young adulthood. In most people, DHEA gradually wanes to negligible levels through older adulthood. Only humans and apes have this characteristic DHEA cycle (1). The function of DHEA is unclear, despite years of research (2).

Supplement manufacturers are using their own interpretations of research reports, along with the fact that DHEA levels drop during aging, to promote their products. They claim that DHEA supplements boost immunity, promote weight loss, build muscle, reduce the effects of aging, and improve mood, memory, and sex drive. The usual recommended dose on the product label is 50 mg per day. Some companies that market DHEA to bodybuilders recommend daily doses of up to 400 mg for an anabolic effect.

DHEA supplements first hit the market in 1985 as a weight-loss aid but were banned by the US Food and Drug Administration (FDA) because they lacked safety and effectiveness reviews (1,3). The ban ended 9 years later with the passage of the Dietary Supplement Health and Education Act of 1994. The law requires the FDA to prove that a nutrition supplement is harmful before the agency can regulate it.

Most DHEA supplements contain DHEA that has been converted in the lab from diosgenin found in wild yams. Some companies market unprocessed wild yam extracts as "natural DHEA" or "DHEA precursors," but unprocessed yam extracts do not convert to DHEA in the body (3). Dietary supplements are not required to meet any government requirements for quality or purity.

Though DHEA has not been shown to increase muscle mass or strength or decrease body fat in young, healthy adults (4), it is banned for athletes by the International Olympic Committee and the National Collegiate Athletic Association as an anabolic agent.

The Search for Benefits

Though there is a large body of research on DHEA, much of the study has been on animal subjects, says Arthur Schwartz, PhD, professor of microbiology at the Fels Institute for Cancer Research at Temple University Medical School in Philadelphia. In rodents, for example, high doses of DHEA prevented obesity, type II diabetes, and tumor development (2). It also reduced anxiety and improved performance on cognitive tasks. Animal studies, however, may have limited value because animals do not mimic human DHEA life-cycle patterns and have negligible levels of endogenous adrenal androgens (2).

Studies in humans have produced some contradictory results. For example, a 1986 study (5) suggested that increased serum levels of DHEA reduce heart disease risk by 50%. But follow-up studies suggested that higher serum DHEA levels increase heart disease risk in women (6) or confer modest protection in men but not in women (7). Other human studies suggest that that DHEA treatment may improve immunity and insulin sensitivity, and may promote antiviral activity in human immunodeficiency virus infection (2), but the studies were small and short-term.

"Many people who take DHEA say it makes them feel well," says Gary I. Wadler, MD, associate professor of clinical medicine at New York University School of Medicine in Manhasset, New York. So far, the most promising effect of DHEA treatment pertains to lupus erythematosus, Schwartz says. He and his colleagues have studied DHEA's role in cancer prevention and treatment of diabetes and lupus. "Clinical trials in California have shown that DHEA does appear to have a benefit in the treatment of lupus: Patients require less prednisone," Schwartz says.

Elizabeth Barrett-Connor, MD, chair of the Department of Family and Preventive Medicine at the University of California, San Diego, says that DHEA also looks promising as a treatment to prevent osteoporosis and depression. Barrett-Connor and her colleagues have studied the relationship between natural DHEA levels in the body and heart disease and osteoporosis.

Schwartz says researchers are working on a form of DHEA that would not break down into estrogen and testosterone, thus minimizing side effects. The compound would be classified as a drug, he says, "and might someday have applications in the treatment of type II diabetes, rheumatoid arthritis, and colon cancer."

Concerns About Side Effects

Side effects of DHEA use may include androgenic effects (acne, oily skin, excessive facial hair growth, voice deepening, hair loss, and mood changes) in women (8). In theory, DHEA, because of its hormonal effects, could stimulate preexisting prostate, breast, and endometrial cancer. DHEA supplements may lead to liver damage, even when taken briefly (9). An additional concern is an increased risk of heart disease in women, says Barrett-Connor.

A few reports in the medical literature document adverse reactions to DHEA. In one report (10), a patient who had advanced prostate cancer was treated with DHEA after other treatments failed. Many of his symptoms improved during DHEA therapy, but his cancer flared dramatically.

Federal policy on DHEA has been inconsistent because the government has classified testosterone as a controlled substance, but not its precursor, DHEA, says Wadler, an internist and sports medicine physician who was the principal author of a book on drugs and sport (11). "It's the supplement du jour, but this one causes me special concern because it's a hormone," he says. "We know a number of serious consequences from increased testosterone and estrogen." Further, side effects of hormone drugs may take months, years, or decades to develop, Wadler says. Examples include osteoporosis from corticosteroid treatment and uterine cancer from estrogen used without progesterone. If DHEA proves problematic in the future, "It will be too late" to protect people who used the supplement, says Wadler.

Last year the National Institute on Aging (NIA), based in Bethesda, Maryland, launched an educational campaign to urge consumers to approach "antiaging" hormone supplements with caution. The agency's concern is based on unsupervised use of DHEA and other hormone supplements, according to a press release from the NIA. The agency says that none of the hormone supplements on the market have been shown to prevent or reverse aging, and that carefully controlled, long-term studies are needed to determine how hormone supplements affect people. (Consumers can call the NIA at 1-800-222-2225 to order a free fact sheet on hormone supplements.) Meanwhile, the NIA is sponsoring several studies on hormone supplements.

What to Tell Patients

Schwartz advises people to avoid DHEA supplements for two reasons. First, compared with higher doses used in animal studies, the recommended supplement dose of 50 mg per day for humans has a remote chance of delivering on manufacturer promises. Second, 50 mg per day still carries a small risk of an androgenic effect in women, he says. "At greater doses, you would definitely have to worry about androgenizing effects."

If patients insist on taking DHEA supplements, physicians should advise them to limit their dosage to 50 mg per day, says Barrett-Connor. Physicians should also inform patients that DHEA supplements have no proven benefits and have side effects, she says. Patients also should know that DHEA products carry no quality guarantees because dietary supplements are not regulated. "For example, one product labeled as DHEA 500 mg—10 times the recommended dose—could have been dangerous," she says. "But it contained no DHEA when tested in the laboratory."

Wadler says male patients who take DHEA supplements should have a prostate exam and have their prostate-specific antigen levels determined; women should have a comprehensive breast exam. Ideally, patients should have their DHEA level determined before starting DHEA treatment to help define a safe baseline. But Wadler says most patients aren't likely to undergo such a test for clearance to take a supplement that is inexpensive and easy to obtain.

References

  1. Skolnick AA: Scientific verdict still out on DHEA. JAMA 1996;276(17):1365-1367
  2. Casson PR, Buster JE: DHEA replacement after menopause? Too early to tell. Patient Care 1997;31(11):147-155
  3. Fontenot B: The hyping of DHEA: long on claims, short on evidence. Nutrition Forum 1998;15(1):3-7
  4. Welle S, Jozefowicz R, Statt M: Failure of dehydroepiandrosterone to influence energy and protein metabolism in humans. J Clin Endocrinol 1990;71(5):1259-1264
  5. Barrett-Connor E, Khaw KT, Yen SS: A prospective study of dehydroepiandrosterone sulfate, mortality, and cardiovascular disease. N Engl J Med 1986;315(24):1519-1524
  6. Barrett-Connor E, Goodman-Gruen D: Dehydroepiandrosterone sulfate does not predict cardiovascular death in postmenopausal women: the Rancho Bernardo Study. Circulation 1995;91(6):1757-1760
  7. Barret-Connor E, Goodman-Gruen D: The epidemiology of DHEAS and cardiovascular disease. Ann N Y Acad Sci 1995;774:259-270
  8. Dehydroepiandrosterone (DHEA). Med Lett Drug Ther 1996;38(985):91-92
  9. National Institute on Aging: Pills, Patches, and Shots: Can Hormones Prevent Aging? Bethesda, MD, April 1997
  10. Jones JA, Nguyen A, Straub M, et al: Use of DHEA in a patient with advanced prostate cancer: a case report and review. Urology 1997;50(5):784-788
  11. Wadler GI, Hainline B: Drugs and the Athlete, Philadelphia, Davis Co, 1989

Lisa Schnirring
Minneapolis


In the Lyme light: new management aids

Lyme disease season is starting in most parts of the country, and this year physicians have new guidelines and reports that shed light on effective and cost-efficient treatment protocols.

Lyme disease diagnosis and treatment are controversial. Several Lyme disease experts say that lab tests and antibiotic treatments are overused. They assert that many physicians rely too heavily on lab tests because they are unfamiliar with the signs and symptoms of Lyme disease, and that patients demand treatment because of anxiety about the disease, leading to the overuse of antibiotics (1-4).

A recent study (5) found that of 209 patients who were presumed (by referring physicians or themselves) to have Lyme disease, 60% had no evidence of the disease. The authors highlighted the pitfalls of overtreatment, which include adverse drug reactions and failure to diagnose and treat underlying conditions, such as depression and rheumatoid arthritis. "We think that many patients and physicians incorrectly view Lyme disease as a chronic and often incurable illness that requires multiple courses of antibiotic treatment," wrote the authors.

In December 1997, the American College of Physicians published a two-part clinical guidelines series (6,7) to clarify who should be tested and treated. Part 1 states that the initial management step should be determining a patient's probability of having the disease, based on clinical evaluation and knowledge of Lyme disease incidence in the patient's geographic area. Testing is usually reserved for laboratory confirmation of late Lyme disease and is contraindicated for patients who have only nonspecific, diffuse symptoms. Empiric antibiotic therapy is recommended for patients who have a high probability of having Lyme disease: those who have arthritis (preceded by brief attacks) or a rash resembling erythema migrans, a history of a similar rash, and a previous tick bite. Part 2 details the laboratory evaluation of Lyme disease.

Several other tick-related developments have made recent medical headlines:

  • A new Lyme-like tickborne illness has been identified. Duke University researchers documented an outbreak of an illness featuring an erythema-migrans-like rash that was spread by Amblyomma americanum ticks at a camp in North Carolina (8). The researchers suggest that a rash that resembles erythema migrans does not confirm the presence of Lyme disease in patients who live in the southern United States.

  • Experts who track tick populations are predicting a higher incidence of Lyme disease this year in the Northeast, and they're not blaming it on el Niño. David Weld, executive director of the American Lyme Disease Foundation in Somers, New York, says the reason is greater numbers of nymphal ticks, the result of a bumper crop of ticks 2 years ago. Deer ticks have a 2-year life cycle. Nymphal ticks are responsible for most cases of Lyme disease because their small size makes them hard to detect.

  • In a report (9) published last summer, researchers showed that oral doxycycline is as effective as parenteral ceftriaxone for the treatment of acute Lyme disease in patients who do not have neurologic symptoms.

References

  1. Bakken LL, Case KL, Callister SM, et al: Performance of 45 laboratories participating in a proficiency testing program for Lyme disease serology. JAMA 1992;268(7):891-895
  2. Schwartz BS, Goldstein MD, Ribeiro JM, et al: Antibody testing in Lyme disease: a comparison of results in four laboratories. JAMA 1989;262(24):3431-3434
  3. Sigal LH: Anxiety and persistence of Lyme disease. Am J Med 1995;98(4A):74S-78S
  4. Sigal LH: The Lyme disease controversy: social and financial costs of misdiagnosis and mismanagement. Arch Intern Med 1996;156(14):1493-1500
  5. Reid MC, Schoen RT, Evans J, et al: The consequences of overdiagnosis and overtreatment of Lyme disease: an observational study. Ann Intern Med 1998;128(5):354-362
  6. American College of Physicians: Guidelines for laboratory evaluation in the diagnosis of Lyme disease. Ann Intern Med 1997;127(12):1106-1108
  7. Tugwell P, Dennis DT, Weinstein A, et al: Laboratory evaluation in the diagnosis of Lyme disease. Ann Intern Med 1997;127(12):1109-1123
  8. Kirkland KB, Klimko TB, Meriwether RA, et al: Erythema migrans-like rash illness at a camp in North Carolina. Arch Intern Med 1997;157(22):2635-2641
  9. Dattwyler RJ, Luft BJ, Kunkel MJ, et al: Ceftriaxone compared with doxycycline for the treatment of acute disseminated Lyme disease. N Engl J Med 1997;337(5):289-294

Lisa Schnirring
Minneapolis


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