Banned for chickens, prescribed to women
'Miracle' drug DES still casts a long shadow 30 years
after doctors stopped giving it to expectant moms.
Many of their children died from cancer or are infertile.
Now there is growing evidence that a third generation may
face the same problems.

ANDRÉ PICARD reports
Saturday, May 12, 2001
ANDRÉ PICARD

Carol Porter was only 22 years old when she was diagnosed with clear-cell
carcinoma, a rare cancer of the genital tract.

She underwent a hysterectomy and, one year later in 1974, a vaginectomy --
operations that scarred her physically and emotionally.

The cancer that stripped Porter of her fertility was caused by DES -- short
for diethylstilbestrol -- a synthetic hormone prescribed to her mother, who
had had a history of miscarriages.

Like almost five million other hopeful mothers-to-be in North America, she
was prescribed DES in 1951 to get her through her pregnancy with Porter.

The "miracle" drug was supposed to guarantee problem-free pregnancies to a
generation of women who were defined by motherhood: It promised no bleeding,
no miscarriages, no premature labours and no gestational diabetes.

Instead, it left users with an elevated risk of breast cancer and, as Porter
well knows, an even bleaker legacy for their children: Some are hobbled by
strange cancers that have killed many as young adults; others have been
robbed of the ability to reproduce.

Half the daughters of DES -- who are now 30 to 60 years old -- have
reproductive problems, most brought on by structural deformities of the
uterus, cervix and vagina. This makes them more likely to suffer
miscarriages, premature births and ectopic pregnancies. As many as one in
1,000 are afflicted with clear-cell carcinoma. And they appear to be at
higher risk for autoimmune diseases such as lupus and rheumatoid arthritis.

Some DES sons have testicular anomalies and are infertile. They also have
elevated rates of testicular and prostate cancer.

Now, 30 years after the drug was discontinued for pregnant Canadian women in
April of 1971, the spectre of DES still lingers. There is evidence that the
women's grandchildren, who are now on the threshold of puberty, face similar
health problems.

Research published last year showed that third-generation female mice
suffered from genital-tract deformities just like their mothers. And a new
study last month found the same is true for third-generation male mice.

"It's really incredible that 50 years after women like my mother took this
miracle drug, DES is still doing a lot of damage," says Porter, a recruiter
for a Toronto law firm.

Despite it all, she remains philosophical, saying her story "has a happy
ending -- relatively speaking." At 49, she is still cancer-free. She "always
wanted to have children," and has satisfied her maternal desires by doting
on her nieces and nephews and by marrying a man with two children.

Still, each day since Porter's hysterectomy 27 years ago begins with
hormone-replacement therapy, a bitter reminder of the "miracle" her mother
was prescribed.

"It's become an invisible story but, for many of us, it's still very real."

Diethylstilbestrol, which mimics the natural estrogen hormone estradiol, was
initially developed in 1938 to fatten up cattle. By 1941, it was also used
in Canada and the United States as hormone-replacement therapy for
menopausal women, and then for those having trouble conceiving.

The idea was that women who could not get pregnant or carry babies to term
simply needed more female sex hormone, estrogen. Testing of the idea, and
DES, was cursory.

>From 1941 to 1971, an estimated 4.8 million women in the United States and
400,000 in Canada were given DES.

Ads in medical journals that featured chubby-cheeked, smiling babies urged
doctors to prescribe it to all pregnant women to ensure "bigger and stronger
babies."

DES was produced by more than 200 companies (though five large
pharmaceutical firms dominated the market) in myriad forms: injections,
pills, suppositories and even as an ingredient in prenatal vitamins.

In an era in which the public was enamoured with medical and technological
advances, seemingly nothing could dampen enthusiasm. DES use persisted in
humans far beyond the dictates of both medical science and common sense.

Research published before DES even went to market showed that it caused
gross genital deformities in the offspring of pregnant rats, but approval
went ahead. Many scientists believed that the placenta was impenetrable, so
no drug -- not tobacco, alcohol or DES -- could damage a fetus. The lessons
of thalidomide, a medication for morning sickness that was prescribed around
the same time and caused children to be born with missing limbs, had not yet
been learned.

A 1952 study showed that the drug did not work for its advertised purpose,
preventing miscarriages, but prescribing continued unabated for two more
decades. Even the banning of DES for agricultural purposes in 1959 -- after
a number of male poultry workers sprouted breasts -- did not prompt a
regulatory review.

"What blows my mind is the glaring contradictions in this story," says
Patricia Stanford, a lawyer in Jacksonville, Fla., who has launched more
than 200 lawsuits related to DES and settled them all out of court.

"Here was a drug that was considered too dangerous for chickens and it was
being given to pregnant women. The dangers were known, but a lot of people
failed in their duties."

A study published in the New England Journal of Medicine in 1971 changed
everything. It began to reveal the invisible deformities of DES daughters,
showing that they were being diagnosed in significant numbers with cervical
and vaginal cancer.

The drug's use was discontinued in pregnant women, but not banned. Today,
DES is still used to treat menopausal women, is sometimes prescribed as a
postcoital contraceptive and is even used to combat prostate cancer. In
animals, its use is permitted for dogs and cats only, but it showed up in
Canadian beef last year.

When Shirley Simand read the first news stories about DES's devastating
effects in Time magazine in 1971, she was alarmed. The Montreal woman
clearly remembered taking DES during three pregnancies, the first of which
ended in a miscarriage. She later had a daughter and a son.

"The nurse came to the house to give me the injections. And later, I got DES
in my prenatal vitamins," she says.

Simand's doctor told her not to worry, but in 1980, her daughter was
diagnosed with clear-cell carcinoma and had a hysterectomy.

"The first thing I felt was this awful guilt. The second was anger, and that
never went away.

"What makes me maddest is that no one ever informed mothers. GM and Ford
recall cars when they have some minor flaw, but nobody ever told Canadian
women that they were given a carcinogenic drug. The whole thing was swept
under the carpet."

Simand channelled the rage into advocacy. She and her daughter formed DES
Action Canada, which has kept the issue alive for more than two decades by
informing women of the dangers of the drug.

The single-mindedness has taken her down some interesting paths. Simand
firmly opposes direct-to-consumer advertising of prescription medication,
staunchly promotes stringent pharmaceutical testing and now warns women
about the risks of hormone-replacement therapy.

"Personally, I will never take those pills because of my experience with
synthetic hormones," she says. "Of course, I think every woman should have
choice, but it should be an informed choice. Prescription drugs have done
enough harm to women."

Menopause has become an important issue as DES daughters approach middle
age. Initially, it was believed that the rare cancers hit only young women
in their teens and early 20s, but gynecologists are now reporting a "second
peak" -- some DES daughters who managed to escape clear-cell carcinoma in
young adulthood are now seeing cancer show up later in life.

Another unknown is whether hormone-replacement therapy is safe for DES
daughters going through menopause. After all, the root cause of their
problems is excessive estrogen. What will happen if they start pumping
hormones back into their bodies?

Then there is the issue of the grandchildren of DES.

Because women are born with a lifetime supply of eggs, scientists speculate
that DES could have damaged their eggs. The drug did not cause a genetic
defect -- that does not seem possible -- but it may have left a genetic
imprint that can be passed on through the generations.

That means that even DES daughters who escaped the cancer and overcame the
fertility problems may see their children face those risks anew.

The third generation of DES descendents is just now approaching puberty, and
50-year-old Michael DuBow is worried.

The McGill University professor of molecular genetics was diagnosed with
prostate cancer when he was 27. Developing an old man's cancer at such a
young age is believed to be another legacy of DES.

DuBow's mother had five miscarriages and was being treated aggressively with
the drug from his conception to birth.

Unlike many other DES sons, he did not suffer from fertility problems. But,
as he enters the age of uro-genital problems, he worries about a return of
prostate cancer.

And as he watches his two daughters, aged 8 and 10, practise their figure
skating, DuBow ponders the drug's legacy. They are perfectly healthy at the
moment, but the question is whether they will remain so at puberty, when a
surge of estrogen will course through their bodies.

"No one knows what to expect with daughters of the next generation. Fifty
years after my mother took this drug, there are still unknowns," DuBow says.

"It's like the sword of Damocles that's always there, hanging over three
generations."


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