Healthy Skepticism International News

May 2006

DES & Disease Mongering: “How I started HRT at a very young age”

Marian Vickers is a DES daughter and founding member of DES Action Australia, a support and advocacy group for people exposed to DES and similar hormones. Established in 1979, DES Action Australia is unfunded and relies on the voluntary efforts of its members. The author declares that no competing interests exist and she received no funding for this article. Her work for DES Action Australia is voluntary and is carried out around her paid employment and family commitments, usually late at night or at weekends.

Abstract

The DES story is not only about a pharmaceutical disaster, it also provides a sobering and clear example of disease mongering over the decades.

DES was the first cheap synthetic oestrogen developed that was able to be taken orally. What followed was decades of disease mongering: a profitable product in search of an ongoing market.

Over the years DES has been marketed as a treatment to prevent miscarriage; as a pregnancy tonic; as (conversely) the morning-after contraceptive pill; as a treatment for acne; and as a quick way to dry up breast milk. Even ‘tallness’ in young girls was considered a disorder requiring drug therapy.

In 1971 in utero exposure to DES was causally linked to the development of a virulent clear cell cancer of the vagina and cervix in young women. Since then a wide range of health outcomes have emerged affecting both men and women, including infertility, reproductive tract cancers and abnormalities, and immune system disorders.

DES is now recognised as an endocrine disruptor and, as such, causes multiple, serious and often totally unexpected adverse health outcomes. These are not immediately apparent but are manifested many years (often decades) later.

The DES story shows disease mongering has been around for as long as the pharmaceutical industry itself. The reason it has proliferated is that the pharmaceutical industry, unlike other industries, has never been held publicly accountable for its faulty products and misleading advertising.

DES, di-ethyl-stilboestrol, or stilboestrol as it is more commonly known, is a synthetic oestrogen. Synthesised by British scientist, Sir Charles Dodd, DES was not patented. In fact he published the formula in an article in Nature in February 1938. It was the first cheap synthetic oestrogen developed that could be taken orally. Despite extensive published research with animals linking oestrogen use with cancer, particularly mammary and cervical cancer, in 1941 DES was approved by the (US) FDA for the treatment of menopause. [1]

Over the following decades DES and other oestrogen products were marketed and prescribed for a diverse range of conditions. What these uses have in common is that they were all experimental, they usually didn’t work, and they frequently had serious, often unexpected, long-term health outcomes for the women and men involved.

What follows is an overview of the disease mongering associated with DES over the decades

DES: Miscarriage Prevention and Pregnancy Tonic
Shortly after it was developed, DES was being touted as a treatment to prevent miscarriage. Let’s be very clear here: this was not based on any scientific research and DES did not prevent miscarriage. In fact Dodd himself wrote to an early advocate of this treatment pointing out that DES administered to pregnant rats and rabbits increased the rate of miscarriage.

In the early 1940s DES was promoted as a treatment of imminent miscarriage, of late pregnancy complications and for high risk pregnancies, such as with diabetic women. Later DES was being marketed as a treatment to prevent miscarriage. That is, the market was widened to include all women with a history of miscarriage. [2]

Incidentally, when you look at these medical journal articles, they invariably list pharmaceutical companies as assisting the research, providing the pills, offering free trials of DES to interested physicians.

By 1949 there was a considerable shift with DES suddenly being recommended as beneficial for any pregnancy. A study was published using first time mothers as the subjects. In an attempt to be ‘scientific’ and have the two study groups as homogenous as possible, all high risk pregnancies were excluded from the study. The selection of ‘normal’ primigravidas as subjects had far-reaching ramifications for the subsequent clinical use of DES, as did the comments on DES babies being “healthier and stronger” and that DES “appeared to render normal gestations ‘more normal’.” [3]

A large scale, randomised clinical trial published in 1953 found that DES was no more effective at preventing miscarriage than bed rest. While the researchers noted that the miscarriage rate was higher in the DES treated group than the control group, they concluded that “the total number of patients was too small to be statistically significant.” [4] A reanalysis of the data using modern statistical methods found that, although the women receiving DES were 1.8 times more likely to miscarry than the control group, this was not statistically significant simply because the overall sample size was too small. The number of subjects had been arbitrarily picked and, based on current statistical knowledge and criteria, it is now known a much larger sample size was required to handle the number of study variables and subset analyses. [5, 6]

However by this time DES was being marketed as a ‘pregnancy tonic’, mixed with vitamins and recommended for all pregnancies. In fact, many DES mothers (women prescribed DES while pregnant) believed they were taking vitamins. An example of this is the 1957 advertisement for DESPLEX - DES is now mixed with vitamins and minerals, and “recommended for routine prophylaxis in ALL pregnancies.”

The Australian version of this was a popular brand called Diesavite. It contained a range of vitamins and minerals and, oh yes, 25 mg of stilboestrol. So effective was the marketing to doctors of this ‘pregnancy tonic’ that it appears many doctors thought they were prescribing vitamins only.

Then in 1971 came the finding that DES exposure in utero was linked to the development of rare, aggressive clear cell cancer of the vagina and cervix in young women. [7]

Latent, invisible, unexpected and deadly
Up until this time it was believed that any harmful effect of in utero drug exposure would show up at birth, based on the thalidomide model of ‘birth defects’. With DES and clear cell cancer, the adverse outcome was not readily apparent but was manifest decades after the original exposure.

And that was only the start of the bad news. Since 1971 more and more serious adverse outcomes for both men and women have emerged (and still are emerging) over time, as outlined on our website: www.desaction.org.au        

DES is now recognised as an endocrine disruptor and, as such, is characterised by multiple, serious adverse effects that are not immediately apparent but are expressed many years later. These effects are unexpected, irreversible and appear to be trans-generational. [8, 9]

DES: Suppression of Lactation
I must admit I find this is one of the strangest uses of DES. For many years, particularly during the 1960s and 1970s, stilboestrol was routinely prescribed to dry up breast milk if the mother had suffered a pregnancy loss or stillbirth, or wished to bottle feed, or was a relinquishing mother. One midwife described the hospitals as “awash with stilboestrol” during the early 1970s - the same time, incidentally, that DES was established as a proven carcinogen in humans.

Of concern to us is the number of women who were subjected to this treatment 20-25 years ago and who have now developed breast cancer. This is probably not that surprising when you consider that DES mothers have a statistically significant increased rate of breast cancer. [10]

DES: Morning After Contraceptive Pill
The safety and efficacy of this treatment has never been proven. To me it beggars belief that a massive dose of a known endocrine disruptor is prescribed to young girls and women, particularly in a time of crisis when the immune system is possibly compromised, such as after sexual assault.

DES: Treatment of Acne
The safety and efficacy of this treatment has never been proven and yet this appears to have been quite a common practice, particularly in the 1960s and 1970s. Again, one has to question the wisdom of giving a potent hormone to young teenage girls at a time when their own hormone cycles are undergoing change and very susceptible to disruption.

DES: Treatment for ‘Tall Girls’
To treat young healthy prepubescent girls with a known carcinogen to stunt their adult height sounds like a bizarre science fiction experiment, but it is unfortunately true.  The rationale was that the treatment was for psycho-social reasons - so they could do ballet, buy clothes more easily, and find boyfriends. Obviously little consideration was given to the psycho-social effect on a young girl of nausea, the immediate onset of menstruation, the sudden development of breasts, and sudden rapid weight gain. And of course the long-term health outcomes of this treatment were never a consideration. The only long-term outcome considered was adult height. When meeting the tall women who underwent this treatment, it is reasonable to conclude the treatment did not work.

We first heard of this strange experiment in the early 1980s when DES Action was contacted by individuals who had undergone this treatment, and who were now experiencing health problems (such as breast and cervical cancer) as young adults. We wrote to both the Royal Children’s Hospital, Melbourne and the state Health Department seeking more information. Both denied any knowledge of such a treatment. In fact we were requested to attend a meeting in at the Health Department where our representative was reassured, at great length, that no such treatment had ever occurred. It was only after media coverage in mid 1997 that the truth was revealed and Tall Girls Inc was formed. [11, 12, 13, 14, 15, 16, 17, 18]

After successful lobbying, the Tall Girls group achieved one of its primary aims of having an epidemiological study undertaken. In 2000 the NHMRC funded a small study into the long-term biological and socio-psychological effects of oestrogen treatment to reduce the adult height of tall girls. The NHMRC originally rejected the proposal but funded it after there was considerable international interest in the study. [19, 20]

Lack of Accountability: They recall cars, don’t they?
Eighteen months ago DES Action Australia members celebrated our 25th anniversary. It was a time of reflection and thinking about what we had learnt over that time. What we all felt was that our experience with DES represented a loss of innocence.

I had always thought (naively as it turned out) that all prescription medicines were safe. And, further, if a drug was suddenly found to be harmful, I thought you would be informed. After all, they recall cars if they are found to be faulty, if they put lives at risk. Or the health authorities recall and issue public warnings if, for example, salami is found to have salmonella.

Why is the pharmaceutical industry the exception?

Lack of Research: “Absence of Evidence isn’t Evidence of Absence”
It may interest and surprise you to realise that (with the exception of the Tall Girls study) there has never been any research into DES usage in Australia. It is outrageous that we simply don’t know the extent of the problem: where DES was prescribed, when it was prescribed, how many people in Australia are DES exposed, and the long-term health outcomes of such exposure. That is, we don’t know the extent of the harm done by the pharmaceutical industry with this faulty and dangerous product.

The pharmaceutical industry needs to be held accountable. If a drug is found to be faulty, to do harm, the industry should pay for the recall, pay for publicising the dangers and alerting those at risk, and pay for ongoing research into further adverse outcomes as they emerge in the future.

It is depressing to realise how ‘political’ medical research funding is, and even more depressing to realise how much of it is funded directly or indirectly by the pharmaceutical industry - and the pharmaceutical industry is not going to voluntarily fund research into its ‘mistakes’. And if we don’t acknowledge our mistakes, we don’t learn from them.

The DES story highlights the shortcomings of evidence-based medicine - this paradigm assumes that research is being carried out and risks determined. The lack of research means that “absence of evidence (of adverse outcomes) isn’t evidence of absence.” If there is no research being carried out, there is no evidence either way - that it, there is no evidence of safety and no evidence of risk.

Probably the greatest worry for DES daughters and DES sons fortunate enough to be able to have children is the possibility that the effects of DES are trans-generational. Researchers at the (US) National Institute of Environmental Health Sciences, using sophisticated animal modelling, have demonstrated that adverse effects of DES are passed down to DES ‘grandchildren’ mice. 21, 22

When we voice our concerns about possible risks to our children, we are confidently told “there is absolutely no evidence” of any such a risk. Well, of course not! There is absolutely no research being carried out! In Australia, the DES third generation (like the DES first and second generations) haven’t even been identified, much less monitored and researched.

It is no doubt comforting to view the DES story as an historical example, that it was an isolated case, and that it could never happen today.  However, the DES experience highlights the limitations of randomised clinical trials (RCTs) and the reporting of adverse drug reactions, the lynchpins of drug safety in Australia. With endocrine disruptors there are multiple, serious, often unexpected ‘adverse reactions’ that are not readily apparent but are manifested many years, and possibly generations, after the original exposure. No RCT will ever pick up these sorts of unexpected and latent outcomes. 

Not Learning From Mistakes = History Repeating Itself
The real danger is that the failure of the pharmaceutical industry to acknowledge its mistakes, to learn from those mistakes, means that history may be repeated.

HRT: DES Revisited
Members of DES Action had a strong sense of deja vu back in 2002 when the controversy erupted about HRT. Here was a drug treatment touted as a ‘wonder drug’, prescribed in good faith and taken by hundreds of thousands of women over many years, and then a large-scale scientific study not only fails to verify its efficacy but the study is stopped because of risks associated with its use. I was struck with the similarities between this and the controversy with DES use in pregnancy almost 50 years before, when the 1953 study raised questions about its efficacy. The notable difference is that in 1953 there was no media coverage of the controversy.

HRT has all the hallmarks of exposure to an endocrine disruptor. What was particularly surprising was that it was the combined oestrogen/progestin treatment that was implicated the most. From the 1960s women were reassured that the addition of progesterone with oestrogen safeguarded against many of the adverse outcomes associated with oestrogen-only use. The real worry of the HRT findings is the implications it carries for the use of the oral contraceptive pill.

Meet Diane, Brenda, Juliet, Estelle…

I first read about Diane-35 in a 2003 article outlining the concerns of a Canadian women’s health group about its use and the marketing techniques being employed.  Advertising of Diane-35, a hormonal drug approved in 1998 in Canada to treat severe systemic acne, was targeting young girls and increasingly being promoted as an oral contraceptive pill. The drug had been used for birth control in Europe, but its use was restricted to acne in 1995 because of liver toxicity. It was also noted that NZ, the UK and Canada have all posted warnings of risks of potentially fatal blood clots. 23

I was reminded of this article some months later when I asked my (then) 20 year old daughter about her friend who had been suffering from symptoms relating to poly cystic ovary syndrome and had suddenly developed acne. This was not systemic acne but rather just break out acne, probably relating to her hormonal cycle being out of sync.

“Oh, her GP has just switched her to a new (oral contraceptive) Pill that’s meant to help with her skin.” 

“It’s not Diane-35 is it?”

“Yeah, that’s it… All my friends are on it, it’s meant to be really good.”

“You’re not taking are you?”

“No… I’m on Brenda, it’s the same thing only cheaper.” !!

Now 2 points come to mind:

1. Where was the Therapeutic Goods Administration on this?

How come a drug that’s use as a contraceptive is restricted in other countries, and has been linked to liver toxicity and blood clots, is being prescribed as an oral contraceptive so freely in Australia? Not only that, as “all my friends are on it”, it may even be the drug of choice of GPs when it comes to prescribing the Pill to young women.

2. When had this name change occurred?

When I was young, the Pill had names like NeoGynon.  A quick look through the MIMS under ‘oral contraceptives’ reveals not only Diane and Brenda, but also Juliet and Estelle.

Surely this targeting of young women, and the use of friendly and innocuous brand names, is the pharmaceutical equivalent of the alcohol industry’s marketing of pre-mixed alcoholic drinks such as spirits mixed with soft drink, the vodka and milk products, and so on.

As a community we are outraged and quick to criticise the alcohol and tobacco industries for these marketing tactics - but not the pharmaceutical industry. It is immune from such scrutiny and accountability.

And this is why disease mongering is flourishing.

The DES story shows that disease mongering has been around for as long as the pharmaceutical industry. A way to combat disease mongering is for the community and the medical profession to be informed of the full extent of the pharmaceutical ‘mistakes’, and by subjecting the pharmaceutical industry’s claims and marketing techniques to the same scrutiny afforded any other industry.

In the state of Victoria all tobacco products sold are subject to a tax that the Health Promotion Foundation (now called Health Promotion Victoria) administers and allocates to fund research and health promotion projects. Maybe the way to combat disease mongering is for the pharmaceutical industry to be levied say 1% of its annual profits and that money be used to research the long term outcomes of faulty products, as well as funding information and health promotion campaigns. For every ‘Restless Legs Awareness Campaign’ or ‘Female Sexual Dysfunction Seminar’ promoted by the pharmaceutical industry, perhaps there could be an ‘Oestrogen Myth Exploded Seminar’ funded or an ‘Endocrine Disruptors Research Centre’ established.

In conclusion, I’d like to quote Barbara Seaman from The Greatest Experiment Ever Performed on Women: Exploding the Estrogen Myth (p5):

“I call the marketing, prescribing, and sale of these drugs an experiment because, for all these years, they have been used, in the main, for what doctors and scientists hope or believe they can do, not for what they know the products can do. Medical policy on estrogens has been to “shoot first and apologise later” - to prescribe the drugs for a certain health problem and then see if there is a positive result.”

We in DES Action can only agree, and we are still waiting for the apology.

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