Biomedical Bulletin

NEWS IN BRIEF

Biomedical Bulletin
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DHEA Helps Women with Lupus
Hormonal factors play a major role in this serious autoimmune disease

ome things in life just aren’t fair, such as the fact that women of childbearing age are 9 times more likely than men to fall prey to systemic lupus erythematosus (called lupus for short). Lupus is a serious, potentially fatal, autoimmune disease—a disease in which, in a cruel irony, your body’s immune system mistakes parts of your own body as foreign invaders and attacks them. Lupus causes painful and swollen joints, skin rash, mouth ulcers, kidney damage, and pericarditis (inflammation of the membranous sac that encloses the heart), among other symptoms.

Unlike most chronic diseases, lupus is not age-related—in fact, its incidence declines with age, and the female-to-male ratio also declines, from 9:1 in young adults to about 3:1 in the elderly. Actually, the first of these age effects applies only to idiopathic lupus, i.e., lupus of unknown origin. Many cases, however, are caused by a variety of prescription drugs, and the incidence of these cases increases with age, probably because the elderly use many of the causative drugs.1

DHEA Levels Are Very Low in Lupus

Lupus is customarily treated with NSAIDs (nonsteroidal anti-inflammatory drugs), including COX-2 inhibitors, and corticosteroids. The most abundant corticosteroid in our circulation is the hormone dehydroepiandrosterone (DHEA). Aside from being a precursor to the male and female sex hormones, its role in human physiology is largely unknown, but it’s believed to help strengthen the immune system and improve endothelial function (see the news brief on page 22). DHEA levels decline sharply with age, and in patients with lupus, they are reduced further, to about 50% of normal.2


The results showed a statistically and
clinically significant benefit from the
therapy: 59% of the women on
DHEA were responders.


Stringent Test for DHEA

It has long been known that DHEA can alleviate the symptoms of lupus in mild to moderate cases. A team of researchers at 27 institutions throughout the United States recently completed a randomized, double-blind, placebo-controlled study of the effects of DHEA on 381 lupus-afflicted women (average age 44).2 The women received 200 mg of DHEA (a high dosage) or placebo daily for 1 year, with examinations every 3 months to evaluate their status.

The objective was to determine the proportion of “responders,” defined as patients who showed improvement or stabilization in lupus disease activity and constitutional symptoms, without clinical deterioration (reflecting organ damage) over the duration of the study. The authors stated that this study was the first of its kind to integrate all three lupus domains—disease activity, organ damage, and health-related quality of life—in the analysis. It thus represents perhaps the most stringent test yet for the benefits of DHEA in treating lupus.

DHEA Provides Significant Benefit

The results showed a statistically and clinically significant benefit from the therapy: 59% of the women on DHEA were responders, versus 45% of the women on placebo.* (The high response rate for placebo reflected the fact that most of the women were receiving standard therapies for lupus during the study.) The DHEA was generally well tolerated; the most common adverse events were acne and hirsutism, which were typically mild and treatable (they are less likely to occur with lower dosages, and if too problematic, they can be reversed simply by abstaining from the supplement).


*It’s important to note that this study included women only. The results observed might not be seen in men, because it’s common for steroid hormones to act differently—sometimes oppositely—in men and women. Nothing should be taken for granted.


I3C Improves Women’s Estrogen Metabolism . . .

Although it’s not yet clear, women suffering from lupus may also benefit from a supplement of a different kind: indole-3-carbinol (I3C), a compound derived from cruciferous vegetables, such as broccoli, cabbage, and cauliflower. I3C is known to reduce the biological activity of estrogens (female sex hormones). This is important because excessive estrogenic activity is implicated in cancers of the breast and reproductive tract in women, and of the prostate gland in men (see the news brief on page 23). The risk for these cancers depends in part on the ratio of two particular estrogen metabolites in our bodies, one of which has strong estrogenic activity and the other of which does not. I3C alters this ratio favorably, i.e., toward lower estrogenic activity.

Because there is reason to believe that excessive estrogenic activity plays a role in lupus, a team of American researchers investigated whether I3C would affect estrogen metabolism in women with this disease.3 They recruited 17 women (average age 38) with lupus and gave them 375 mg of I3C daily for 3 months (the women were advised to avoid all consumption of grapefruit, which can antagonize the effect of I3C). To the researchers’ surprise (because they had surmised that I3C would not work), the ratio of the two estrogen metabolites in question rose from 1.84 to 3.15 after 1 week—a 71% increase that indicated a strongly positive effect of I3C.

. . . Which Could Benefit Women with Lupus

Despite this favorable result, the researchers observed no significant improvement in the women’s condition over the ensuing 3 months of the study. Whether this lack of effect is inherent with lupus or the result of the study’s shortcomings (small number of subjects, not placebo-controlled, short duration) remains unclear, and the authors recommended further study to clarify the question. They stated,

We conclude that I3C does exert metabolic influences on estrogen metabolism in women with SLE [systemic lupus erythematosus], which could benefit women with this disorder.

For more information on DHEA, see “DHEA: The Most Versatile Hormone” (February 2001), “Stopping the Biological Clock in Postmenopausal Women” (December 2001), and “DHEA Helps Restore Hormonal Balance” (March 2004). And for more information on I3C, see “Achieving a Healthy Sex-Hormone Ratio” (October 2000) and “The Gene Connection in Preventing Estrogen-Related Cancers” (March 2001).

References

  1. Beers MH, Berkow R, eds. The Merck Manual of Geriatrics, 3rd ed. Merck Research Laboratories, Whitehouse Station, NJ, 2000.
  2. Petri MA, Mease PJ, Merrill JT, et al. Effects of prasterone on disease activity and symptoms in women with active systemic lupus erythematosus: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2004;50(9):2858-68.
  3. McAlindon TE, Gulin J, Chen T, Klug T, Lahita R, Nuite M. Indole-3-carbinol in women with SLE: effect on estrogen metabolism and disease activity. Lupus 2001;10:779-83.

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