DES Linked to Birth Defect in Grandsons

Fri Mar 29,10:14 AM ET

By Merritt McKinney

NEW YORK (Reuters Health) - Grandsons of women who took the drug diethylstilbestrol, or DES, during pregnancy may be more likely to develop an abnormality of the penis, according to a new study.

The drug is known to be harmful to children exposed to it in the womb, but the health effects on later generations have been uncertain.

"For the first time, a third generation effect of DES has been found in humans," the study's lead author, Dr. Flora E. van Leeuwen of the Netherlands Cancer Institute in Amsterdam, told Reuters Health.

For decades, DES, a synthetic hormone that mimics the effects of estrogen, was prescribed to pregnant women to prevent miscarriages and premature labor. In the early 1970s, however, several studies detected an increased risk of cervical and vaginal cancer in women who had been exposed to DES in the womb. Use of the drug in pregnant women was halted in 1971 in the US and in 1978 in Europe.

DES has been linked to other health problems in people who were exposed to it before birth, including genital cancers and infertility in women. The harmful effects of the drug seem to have been less common in men, but some researchers have reported increased rates of urinary-tract and genital defects in men whose mothers took DES.

Whether the harmful effects of DES persist into future generations has been uncertain. Based on a study that suggested that the grandsons of women who took DES were more likely to be born with a defect called hypospadias, van Leeuwen and her colleagues conducted a study to investigate the possible link.

Hypospadias occurs when the opening of the urethra is not located at the tip of the penis, but instead on the underside of the shaft or on the scrotum. Two to six of every 1,000 boys in the US are born with the condition, which can be corrected with surgery. If left untreated, it can cause problems with urinary and sexual function.

Out of a sample of more than 16,000 mothers, Van Leeuwen's team identified 205 boys whose mothers had been exposed to DES in the womb. Four of these boys had hypospadias compared with eight of nearly 9,000 boys whose mothers had not been exposed to DES. Based on this sample, the researchers calculated that the rate of the abnormality was about 21 times higher in the sons of DES-exposed mothers.

The findings are published in the March 30th issue of the medical journal The Lancet.

"Much more research is needed in this field," according to the Dutch researcher, not only to confirm the findings in larger numbers of people but also to understand the biological mechanism behind the defect.

Van Leeuwen added, "Research on long-term effects of medications in general should become a priority for governments and funding agencies."

The report is "intriguing," but it does not yet prove that DES causes hypospadias in the grandchildren of women who took the hormone, according to Dr. Sonia Hernández-Diaz of Boston University School of Public Health in Massachusetts. Still, even though the hormone is no longer used, research on its effects "may be relevant to current concerns about exposures to weaker estrogens such as synthetic hormones present in oral contraceptives, phyto-estrogens in the diet or certain pesticides," Hernández-Diaz notes in a related editorial.

"Knowledge gained from the diethylstilbestrol debacle should be used to guide research on the possible risks associated with estrogens that are being encountered by current generations," she concludes.

SOURCE: Lancet 2002;359:1102-1107,1081-1082.