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DES effects run deeper than feared

By Jennifer Durgin

A drug banned over 30 years ago still has implications today, a DMS epidemiologist is discovering. For 15 years, Linda Titus-Ernstoff, Ph.D., and a team of researchers around the country have been studying the long-term effects of diethylstilbestrol (DES)—a powerful synthetic estrogen once prescribed to millions of pregnant women in the United States. The dangers of DES, Titus-Ernstoff is finding, may extend further than anyone previously thought.

From about 1940 through the early 1970s, doctors commonly prescribed DES to reduce the risk of miscarriage—despite studies showing that it was potentially harmful and ineffective. The drug was finally banned in the early 1970s, when many of the prenatally exposed daughters developed an extremely rare vaginal cancer. Since then, researchers, including Titus-Ernstoff, have revealed numerous other side effects of DES: an increased risk of breast cancer in women who took DES while pregnant; of reproductive-tract abnormalities, menstrual irregularities, infertility, adverse pregnancy outcomes, and breast cancer in women who were prenatally exposed; and of urogenital abnormalities in men who were prenatally exposed.

Most recently, Titus-Ernstoff and her colleagues have found evidence that the children of the prenatally exposed may have DES-related abnormalities, too. While the drug "doesn't seem to create

Titus-Ernstoff is looking into generational ripples from the use of DES decades ago.

genetic mutations," says Titus-Ernstoff, "it may change gene expression in the prenatally exposed . . . and those changes in gene expression may be transmitted to the next generation." If proven, this would be a revolutionary finding in genetics, epidemiology, and numerous other fields. But, she is quick to caution, "these are very preliminary results. . . . Take it with a grain of salt until it's confirmed" by more research. Titus-Ernstoff is among those pursuing such research, as the lead

investigator for a National Cancer Institute-funded study.

Impact: Whether these findings are confirmed or not, the DES saga is important as "a model for environmental and pharmaceutical estrogens and their impact," she says. "We can get estrogens through the environment, through our diet, through pesticide exposure . . . [or] pharmaceutically. [And DES] gives us some idea of what estrogen does when a fetus or embryo" is developing.

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