A WONDER DRUG GONE BAD DES WAS PRESCRIBED TO PREVENT MISCARRIAGES - BUT ITS LEGACY IS ONE OF UNTOLD TROUBLE.

Byline: Mariko Thompson Staff Writer

The advertisement for diethylstilbestrol, a synthetic estrogen, was a picture of health. Aimed at doctors, the ad promised to prevent miscarriage and showed a bright-eyed baby with a pudgy finger in its mouth. And as an added benefit, the tablets even contained vitamin C and vitamin B complex.

That was 1957, 11 years before the Food and Drug Administration warned doctors to stop prescribing diethylstilbestrol, or DES. Not only did the drug fail to prevent miscarriages, but it caused rare cancers and defects in the reproductive organs, particularly in the daughters of women who took the tablets.

Prescribed to an estimated 5 million women between 1938 and 1971, DES represents a frightening chapter in medical history. DES daughters say the legacy should not be forgotten.

``There have been profound effects on their health and there continue to be,'' said Nora Cody, executive director of the Oakland-based advocacy group DES Action. ``This is a problem entirely not of their own making, caused by the pharmaceutical industry and the medical establishment. Society owes it to the people exposed to this drug to take responsibility to do the research.''

Web of information

Recently, the Centers for Disease Control and Prevention in Atlanta launched a Web site to educate the estimated 5 million children exposed to DES as well as the doctors who care for them. Advocates say the Web site provides them with a legitimate source of information that they can download and give to doctors who aren't familiar with the aftereffects of DES exposure.

Patti Negri, a 46-year-old Hollywood resident and DES daughter, entered a menopausal state at age 15 and was unable to have children. She often finds that she has to educate doctors about her condition.

``In my whole life of going to doctors, they would look at me blankly,'' Negri said. ``They just didn't know about DES. It's not made up by some hypochondriac woman.''

Since the 1970s and 1980s, the spotlight has shifted away from DES, agreed Candy Tedeschi, a New York-based ob-gyn nurse practitioner who works with DES daughters.

``DES isn't taught as much in medical school anymore,'' Tedeschi said. ``Among the doctors graduating in the last 20 years, it's harder to find doctors who are knowledgeable about it.''

The use of DES, sold under myriad brand names, was most widespread in the U.S. between 1946 and 1960. Many people don't even know they were exposed. No medical tests exist to detect exposure. Many mothers don't remember what they took while pregnant. And tracking down old medical records can be a chore, if not impossible, Cody said.

Tracking the risk

People who don't have medical problems associated with DES exposure probably don't need to worry about whether their mothers took the drug. But for those who have suffered from reproductive abnormalities, ``to be able to put a name and reason to the problems can be reassuring,'' Cody said.

Though mothers and sons face increased risks for certain medical problems, exposed daughters appear to have been hit the hardest. Mothers who took DES have a moderate increase in the risk of breast cancer. Only a few studies have looked at health effects on DES sons, who have an increased risk of noncancerous cysts on the testicles. Though some genital abnormalities have been reported in the sons, studies have been inconclusive, according to the CDC.

In daughters, DES exposure could cause a rare cancer of the vagina, the finding that led the FDA to issue the warning. The drug also created structural abnormalities in the reproductive tract, including a T-shaped uterus.

Studies have found that DES daughters are more likely to suffer from ectopic pregnancies, miscarriages and infertility problems. Only 64 percent of DES daughters carried their first pregnancy to term, compared to 85 percent of women who were not exposed to DES, according to the CDC.

One question that's difficult to answer is whether the problem of recurrent miscarriages in DES daughters - and now granddaughters - would be genetic or due to the drug, said Dr. Alan De Cherney, UCLA professor of obstetrics and gynecology.

``Is it inherited or is it from taking (DES)? It's the chicken and the egg,'' he said.

The next generation

With most DES daughters beyond their childbearing years, new concerns have emerged. DES daughters over the age of 40 may face a slight increase in risk for breast cancer, but more research is needed. As DES daughters reach menopause, researchers are monitoring them for cancers in the reproductive tract.

Possible health effects on DES granddaughters also are being studied. A National Institute of Environmental Health Sciences study that looked at mice found reproductive tumor growths in third-generation offspring, but experts say it's not yet clear what, if any, implications that will have for humans. So far, the small samples of DES granddaughters who have been checked haven't suffered from ill effects, according to the National Cancer Institute.

``They don't have the same physical changes that the mothers did, and that's good,'' Tedeschi said.

Marilyn Shenker, a marriage and family therapist in Sherman Oaks, learned in the early 1970s that she was exposed to DES. Because of an abnormality in the development of her cervical tissue, Shenker was prone to infections. She underwent four cryosurgeries - treatments which use extreme cold to destroy tissue for therapeutic purposes - but they later made it difficult to get pregnant. Her mother had breast cancer twice and later died of heart disease.

``I remember my mother feeling like she was responsible,'' Shenker said. ``Who knew? You trusted your doctor.''

Last year, Shenker was saddened but not surprised by the news that the Women's Health Initiative halted a large-scale study of hormone replacement therapy when researchers found an increased risk for breast cancer and heart disease. HRT, popularized in the 1960s, was given to more than 6 million American women to treat menopausal symptoms. But the estrogen-progesterone combination didn't pass muster in the randomized double-blind placebo controlled trial.

``I've had a mistrust of medicines'' as a result of DES exposure, Shenker said. ``Especially now that it's so consumer-driven.''

DES daughters interviewed said they are concerned about the current trend of marketing pharmaceuticals directly to consumers. In the heyday of DES, advertisements ran in medical journals and targeted doctors. Today, those same ads might be found in general-interest magazines, on the Internet and on TV, Negri said.

``They go right to the public, and that's even scarier,'' she said. ``We have to be vigilant about drugs not being tested or marketed correctly so that this does not happen again.''

For more information on DES

--Centers for Disease Control and Prevention DES Update: www.cdc.gov/DES

--National Cancer Institute: cis.nci.nih.gov/fact/3-4.htm

--DES Action: (800) DES-9288 or www.desaction.org

--DES Cancer Network: (800) DES-NET4 or www.descancer.org

CAPTION(S):

2 photos, box

Photo:

(1 -- cover -- color) The DES DILEMMA

Two generations later, pregnancy drug's aftereffects still not fully understood

Gregg Miller/Staff Artist

(2) Marilyn Shenker of Sherman Oaks, a DES daughter who has undergone four surgeries due to abnormal cervical tissue

Charlotte Schmid-Maybach/Staff Photographer

Box:

For more information on DES (see text)