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Diethylstilbestrol

Diethylstilbestrol (DES) is a drug, a synthetic estrogen that was developed to supplement a woman's natural estrogen production. First prescribed by physicians in 1938 for women who experienced miscarriages or premature deliveries, DES was originally considered effective and safe for both the pregnant woman and the developing baby. A double-blind study was not done until DES had been on the market for more than a decade (Dieckmann, 1953). more...

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Even though it found that pregnant women given DES had just as many miscarriages and premature deliveries as the control group, DES continued to be aggressively marketed and routinely prescribed.

In the United States, an estimated 5-10 million persons were exposed to DES during 1938-1971, including women who were prescribed DES while pregnant and the female and male children born of these pregnancies. In 1971, the Food and Drug Administration (FDA) issued a Drug Bulletin advising physicians to stop prescribing DES to pregnant women because it was linked to a rare vaginal cancer in female offspring. DES was, however, never banned and was continued to be prescribed in the U.S. and other countries well beyond the 1971 date (1978 in most European countries and even as late as 1994 in some third world contries).

More than 30 years of research have confirmed that health risks are associated with DES exposure. However, not all exposed persons will experience the following DES-related health problems.

Women prescribed DES while pregnant are at a modestly increased risk for breast cancer. A new study shows DES daughters as having a 2.5 fold increase in breast cancer after age 40.

Women exposed to DES before birth (in the womb), known as DES Daughters, are at an increased risk for clear cell adenocarcinoma (CCA) of the vagina and cervix, reproductive tract structural differences, pregnancy complications, infertility, and auto-immune disorders. Although DES Daughters appear to be at highest risk for clear cell cancer in their teens and early 20s, cases have been reported in DES Daughters in their 30s and 40s (Hatch, 1998).

Men exposed to DES before birth (in the womb), known as DES Sons, are at an increased risk for non-cancerous epididymal cysts and auto-immune disorders.

Researchers are still following the health of persons exposed to DES to determine whether other health problems occur as they grow older.

Current research also looks at DES Third Generation. Third Generation refers to the offspring of DES Sons and Daughters. There is not yet much information available because the Third Generation are at an age where they can start to be physiologically affected by the DES exposure of his or her parent(s).

Third generation injuries are associated with preterm labor or deliveries resulting in premature birth and cerebral palsy, blindess or other neurological deficits or death of a child. One DES Daughter had a child who, at the age of four years, had such a severe case of cerebral palsy that the child was unable to turn himself over; the cerebral palsy was linked to the DES exposure of the mother.

Another study (J Pediatr Hematol Oncol 2003; 25:635-636.) found DES to be transgenerational, meaning that the maternal grandmother had taken DES while pregnant but the mother did not experience any health associated with the DES exposure. This was realized when a rare tumor was discovered on a 15 year old girl.

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DES sons show changes in brain function - diethylstilbestrol - prenatal exposure to sex hormones may affect brain development
From Science News, 11/7/92

In the 1950s and 1960s, physicians commonly prescribed a drug called diethylstilbestrol (DES) to prevent miscarriage and premature birth. The safety of the drug, a synthetic form of the sex hormone estrogen, was first challenged in 1971. Since then, numerous studies have found that daughters of women who had taken DES during pregnancy ran an increased risk of developing a rare cancer of the vagina and cervix. For DES-exposed sons, some studies demonstrated a link between the drug and genital abnormalities.

A scientific report in HORMONES AND BEHAVIOR (vol. 26, p.62-75) finds statistically significant evidence that males exposed to DES in the womb may undergo subtle alterations in brain function.

"This is the first evidence in human males that prenatal exposure to sex hormones -- specifically DES -- is involved in the development of both brain organization and sex-differentiated cognitive abilities," says principal investigator June M. Reinisch of the Kinsey Institute for Research in Sex, Gender, and Reproduction at Indiana University in Bloomington.

Reinisch and her colleague Stephanie A. Sanders, also at the Kinsey Institute, began their investigation by recruiting 10 male subjects age 9 to 21 who had been exposed to DES in the womb but who showed no signs of DES-related birth defects. The researchers also recruited 10 male siblings in the same age group who had not been exposed to DES during gestation.

The subjects and their brothers then took the Witelson Dichhaptic Shapes Test, an evaluation that measures brain lateralization, or the tendency to use one side of the brain while completing a task. The participants were first told to reach into a box containing unfamiliar geometric shapes, Sanders explains. After feeling the shapes, the subjects had to match the shapes in the box with those depicted in a picture, she says.

Correct matches among the DES-exposed group were evenly distributed between both hands, a response that is more typical of the way girls and women score on this test. (Men and boys tend to get better scores with the nonpreferred hand.) The brothers in the control group showed the typical male pattern. Both groups got the same number of right answers, Reinisch points out.

It may be that DES-exposed males use both sides of the brain in matching the shapes, a trait most commonly seen in females. That doesn't mean that DES-exposed males are more feminine than their nonexposed brothers, the researchers emphasized. The test results simply mean they go about the task differently than their brothers.

The researchers also administered another test, the Wechsler Intelligence Scales, to the boys and young men in the study. They discovered that the DES-exposed group scored lower than their nonexposed brothers on a spatial component of the test. In that component, subjects have a certain amount of time to find missing parts of a picture, complete a jigsaw puzzle, and perform other tasks that measure spatial ability. Males tend to perform better than females on this component, and the DES-exposed males again followed the feminine pattern.

These results do not suggest that males exposed to DES in the womb are less intelligent than their nonexposed brothers, Reinisch cautions. In fact, the overall IQ test scores for both groups were about the same, she notes.

However, Reinisch and Sanders believe that exposure to DES in the womb does--in a very subtle way -- change the way men approach certain tasks, especially spatial tasks. The researchers believe that by studying DES exposure, they may be better able to understand the powerful effects of natural hormones on the fetal brain before birth. Such research might help explain possible gender differences in the way the human brain functions, they say.

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