PRESS BOOK

Synthesis Note

Distilbène : for the D.E.S France Network association,
It is necessary to act right now

Distilbène (diethylstilbestrol, hormone of synthesis) was prescribed to millions of pregnant women in the world as from 1948. In 1971, it was forbidden in the U.S.A. In France, it was prescribed until 1977.

This treatment which was prescribed without any proof of efficiency, had none of the beneficial effects it was supposed to bring to the development (course) of the pregnancies of these women. On the other hand, it caused serious damage on the child they carried. In our country, 160 000 children, 80 000 of whom are girls, are estimated to be affected.

Now, these "DES daughters", as they are called, belong today to the generation of those who want to have their turn to become a mother : the problems coming from the damage of the genital system of these women do arise now with most acuteness. Techniques and therapies do have to be strictly adapted to their case right now.

Many questions on the known or coming damage from Distilbène are coming now ; for this generation and for those of the future, it is necessary to act right now.

The route of these young ladies is often long and painful to live. Uncertainties and questioning are numerous ; coverage is sometimes laborious, badly administered and even unsuitable.

Because of the urgent need to help this generation not to pay the full price of the errors of the past, the D.E.S. France association Network wished to set up a Scientific Council.

This council, composed of 23 members met on March 28, 2000.

With the cooperation of this council and under its authority, the D.E.S. France Network association launched a series of actions :

• better information of the concerned persons and the health services as well as the elaboration of protocols of care turn out to be essential :
  The Association issued by means of its Scientific Council a series of practical sheets which is intended for them.

• The coverage and the follow-up of the DES-daughters who want to be mothers are not specifically taken into account by the Social Security :
  The DES France Network association and its Scientific Council made an urgent request in this sense to the Management of Concerned Services.

• A surgical operation, called "hystéroplasty to enlargement ", has been proposed more and more frequently to some of these women without having been really estimated :
  The Association and its Scientific Council remind that an evaluation is essential ; they decide to set up an evaluation of this technique and advise to reserve this intervention for the situations in which all the other usual means did not allow to end in a successful pregnancy.

• Will Distilbène have a fatal action also on the third generation ?
  The Association asked the Scientific Council to review current knowledge. This question has to be studied precisely but the results of already carried out experiments do not allow to answer.

• Does Distilbène also have psychiatric effects on the children of some of these women ?
  Because of the imperfections of already published studies, the Association and its Scientific Council decided to participate in an investigations program whose first phase is to define the way researchers and victims of the D.E.S. are going to cooperate.

SCIENTIFIC COUNCIL
of the D.E.S. France Network Association

The generation of the D.E.S. daughters born in the years 68/70 is now old enough to have a desire for child.

Faced with this sensitive outbreak of problems coming from the damages caused by the D.E.S., the D.E.S. France Network association set up new means of action to help these women. In March 1999, it set up a Scientific council to help it to realize an assessment of knowledge, to estimate pathologies, their consequences and their treatments.
Gynaecology specialists - obstetrics, embryology, psychiatry, epidemiology, health service- helped the D.E.S. Network Association by bringing their knowledge and their experience.

The Scientific council is composed of:

Dr Pierre Arnould gynaecologist obstetrician, Edouard Herriot hospital, Lyons
Dr Jean Belaisch medical gynaecologist, Paul's St Vincent hospital, Paris.
Pr Bernard Blanc gynaecologist obstetrician, CHRU Marseille
Dr Anne Cabau gynaecologist medical, St Vincent de Paul hospital, Paris
Dr Jean-Marie Cohen doctor epidemiologist, Open Rome, Paris
Constance de Champris psychotherapist Network association D.E.S. France
Dr Maryse Dumoulin doctor in public health, doctor in pathology Maternal and foetal in the CHRU of Lille
Dr Elisabeth Elefant embryologist, St Antoine hospital, Paris
Dr Sylvie Epelboin gynaecologist obstetrician, St Vincent de Paul Hospital, Paris.
Pr René Frydman gynaecologist obstetrician, Antoine Béclère Hospital, Clamart
Dr Olivier Garbin gynaecologist obstetrician, CMCO, Strasbourg
Pr Bernard Hedon gynaecologist - obstetrician, CHU, Montpelier
Dr Jean-Marie Kunstmann PH, Laboratory of bio reproduction, Cochin Hospital, Paris
Pr Xavier Le Coutour Public health, CHU, Caen
Anne Levadou president of the D.E.S Network association France
Pr Patrice Lopes gynaecology and medicine of the reproduction, CHU Nantes
Pr Pierre Mares gynaecology - obstetrician,CHU Nimes
Pr Bernard-Jean Paniel gynaecology obstetrician, CICH, Créteil
Pr Emile Papiernik gynaecology obstetrician in the René Descartes University and in the Maternity of Royal Port, Paris
Pr Jean-Claude Pons gynaecologist obstetrician, CHU, Grenoble
Pr Christian Quereux gynaecologist obstetrician, CHU Reims
Pr Michel Tournaire gynaecologist obstetrician, St Vincent de Paul Hospital, Paris.
Pr Hélène Verdoux psychiatrist, Victor Segalen university, Bordeaux 2

THE TECHNICAL FILES
Of the DES France NETWORK Association

As from the moment when the exposure to the DES is suspected or confirmed, the DES-daughter begins a specific route. From the first gynaecological examination to the supervision of the menopause, every stage of woman life will take into account the phenomena linked to this exposure.
For some of them « Distilbène » won’t have any or few effects and simple precautions will be enough to lead a life without problems.
For the others, the consequences will be heavier and they will have to benefit from perfectly adapted care.
Now, often, from consultations of Gynaecology to different examinations which are more or less invasive, from treatments to interventions, they meet many uncertainties and ask many questions.

The Association wishes to give to these women a precise, confirmed, practical and updated information, about every stage of this route:
The practical files describe the situations they meet and the existing treatments, with references from one file to another one when subject requires it.
They have been conceived in a clear language where technical terms are explained. Each subject is treated in a simple but complete way with regard to the current state of knowledge.

Written with the help of the Scientific Council of the Association, they will be regularly updated.

4 technical files are already available :

GYNAECOLOGY-OBSTETRICS OF DES-DAUGHTER : GENERAL POINTS
The possible damage provoked by the DES and gynaecological follow-up which is convenient
for the DES-daughters.
DES DAUGHTERS and FERTILITY :
How can the DES intervene on the fertility of the DES-daughters and which answers we can
give.
FOLLOW-UP OF DES PREGNANCY
The pregnancy of the DES-daughters requires mostly specific follow-up and particular measures.
HYSTEROPLASTY TO ENLARGEMENT
Explanations and opinion of the Scientific Council on this operative technique which has not been valued yet.

ARE THE CARES OF THE DES-DAUGHTERS
CORRECTLY TAKEN BY SOCIAL WELFARE ?

The history of Distilbène is a harmful prescription example. The Distilbène (diéthylstilboestrol, DES) was prescribed without any proof of efficiency to about 200.000 pregnant women until 1977 in France.
The DES daughters born of these pregnancies often have health problems ; some of them have to be taken into account because of the specific damage of the DES. Are their cares correctly taken in charge by the Social Welfare ? Does the undertaking take the consequences of the exhibition to the DES into account ?

The Scientific Council of the association Network DES-France asserts :

• Some of the 80.000 « DES daughters » are suffering from fertility trouble that require in-vitro-fertilization techniques (IVF). The present regulations accept only 4 IVF reimbursements whereas DES daughters often need 5 or even 6 IVF to achieve to a pregnancy.
• When the DES daughters succeed in being pregnant, absolute rest is often imposed to them, meaning a total confinement to bed as from the first weeks of pregnancy, because of the particularly important risks of precocious spontaneous miscarriages and of premature baby.This total confinement to bed imposes a sick leave during the whole pregnancy ; yet, the handling of a stop of this length is not foreseen by the present administrative setting. They don’t even benefit from the easiness granted to the twin pregnancies.
• This non adapted handling is probably responsible for an intolerable « human and financial waste » : sets of expensive but unsuccessful IVF (« they stop when it was about to succeed ») ; pregnancies obtained with hard works and high costs, too often wasted by an insufficient confinement.

Consequently, the Scientific Council has decided to point out these hiatuses of handling to the National Case of Insurance-Illness of the salaried workers (CNAMTS) ; they write to Hubert ALLEMAND, Pr, M.D. Council National to propose 2 measures aimed at fighting against this waste :

1. To accept 6 reimbursements IVF for DES daughters ( the present limit is 4 attempts ).
2. To take in charge the sick leave of the pregnant DES daughters, during the same length and in the same conditions as for the twin pregnancies.

The Scientific Council of the DES France Network association also began to list the imperfections of the present medical follow-up, in order to mark the improvements that should be brought to the handling of the DES daughters. The Council will then issue a protocol of specific medical follow-up of the DES daughters, including among its criteria, the quality of the administrative handling by the Social Welfare.
This protocol, once finalised, will be submitted to the Health Authorities and will then be published.

HYSTEROPLASTY FOR ENLARGEMENT :
An essential evaluation ?

One of the most frequent effects of the DES on the genital part of the "DES-daughters" is to give an hypertrophied uterus muscle, thus deforming the uterus cavity, giving the uterus some particular forms, in particular "the form in T".

Hoping to improve fertility and to decrease the risk of miscarriage or prematurity during pregnancy, some medical teams tried to correct these particularities of the cavity of the uterus, more precisely by cutting the ram muscle responsible for this "T" form. Called "Hypertrophy to enlargement", this simple operation is more and more recommended, because of the hopes its brings.
However, its efficiency and "relevance" have not yet been proved.
What can we think about it ?

The Scientific Council of the DES France Network Association considers that:

• The condition of the uterus before pregnancy is not a reliable factor to differentiate the risk of prematurity (there are not more premature children with women who have that kind of deformation of the cavity of the uterus before their pregnancy).

• The form of the uterus cervix can be a risk factor: when the uterus cervix is very small before the pregnancy (1 cm length instead of 3 cm usually), the risk of premature birth increases.

• This fact led some specialists to stop performing X Rays of the uterus cavity (hysterography) or directs examinations (hysteroscopy).

• We have to check that the Hysteroplasty does not endanger the cervix or the mucous membrane of the uterus.

Therefore the Scientific Council decided that the advantages and disadvantages are uncertain and that an evaluation would be absolutely necessary.

The DES-daughters are already suffering from a treatment which was prescribed without any proof of efficiency. Doctors have to be careful ( It is human to make mistakes, but perseverance would be catastrophic).

The Scientific Council of the DES France Network Association decided to set up an evaluation program of the advantages and disadvantages of this technique with patients and specialists of "hysteroplasty for enlargement ".
While we are waiting for the results of this evaluation, the Scientific Council suggests to keep the "Hysteroplasty for enlargement" only for situations for which all the usual ways to achieve a successful pregnancy have failed.

Will Distilbène also have an effect
on the 3rd generation ?

In the US where research began a long time ago, publications (also in Holland and in Canada) exposed the increasing risk of cancer to the grand children of mice who were exposed to Distilbène in utero.

The DES France Network Association, (who pointed out that the problem was also apparent among its members), couldn't help wondering whether this research would allow them to conclude that the effect of Distilbène on the grand children of women who took Distilbène during their pregnancy, is in fact a real risk.

Consequently, the Association asked its Scientific Council to sum up the situation and this subject was the topic of a speech from Doctor Elisabeth Elefant (embryologist at the Saint Antoine's hospital in Paris) during the Council's annual meeting in March.

It was said that :

The described experimental results pointed out some questions which need to be studied very closely.
At present, the problem has only been studied on mice, which is not enough to draw any conclusion.
The dosage given to mice is massive in comparison to that given to women and therefore the results cannot represent the same impact.
Finally, hypofertility (a recognised effect of the DES) diminishes the number of subjects tested for each generation, and it has an influence on the calculations and the conclusions drawn from these calculations.

In conclusion:

The studies which exposed the problems are of good quality but the results should be confirmed on other species with varying dosage levels along with other protocoles before an advantageous outcome for the humans can be concluded.
At present time, it is impossible to confirm anything at a human level.

Does Distilbène also have psychiatric effects ?

Some of the children born of women who took Distilbene during their pregnancy now show signs of psychiatric damage - sometimes serious. Can we attribute this to Distilbene ?

After pointing out the problems which appeared on some of its members, the DES France Network Association asked its Scientific Council to sum up the problem. This was the subject of a speech of the Professor Helene Verdoux (Professor of psychiatry at Victor Segalen University at Bordeaux 2) during the Council's annual meeting in March.

It was said that :

Some psychiatric diseases such as schizophrenia or depression are much more frequent than the cases of exposure to Distilbène. It is not surprising that some "DES-children" suffer from these diseases just like other children not exposed to DES.

About 10 studies aimed to show a high risk of accrued psychiatric damage among the DES children. The results, published from 1983 to 1995, do not allow to conclude whether DES has a definite impact on the nervous system or not.

However, Distilbène belongs to a group of hormones which are important during pregnancy for the development of the nervous system of the foetus. Therefore, we have to continue our research on this issue.

To conclude:

Because of the imperfections of the previous studies, we cannot confirm that the exposure to Distilbène has psychiatric effects on the children of women who took Distilbène during their pregnancy.

That is why the DES France Network Association and its Scientific Council decided, with the assistance of “l’Agence Francaise de la Séurité Sanitaire "(AFSSAPS), to begin a series of studies, some of which on the psychiatric effects of Distilbène. In order to obtain studies of good quality, it is important that researchers and victims of DES preserve good relationships.
The first phase of this research consists in getting in touch with the members of the DES France Network Association in order to define how they will collaborate with the researchers.

TESTIMONIES

Extracted from " Solidarités D.E.S. "
Association End-of-term report

" (... ) I feel very alone faced with this problem … It is a sensitive subject I still find hard to explain especially to my family and my circle of friends. My mother, who is nevertheless so close to me, feels enormously guilty. Yet, she never made any secret of the fact that she took Distilbène as well as its consequences, which were observed afterwards. I can’t hide you that I really need a support in front of this problem ; I didn’t succeed in finding any support from the medical profession "

" ( … ) I haven’t given up for 5 years made of hope, tears, confusion, sadness ( a sort of assault course). I want to take revenge on Distilbène. I pay for the right to live. I pay for the right to procreate. "

" A little push in the right direction for the D.E.S.daughters who haven’t have any baby yet. A fit of rage against administrations, such as the CAAF, the Social Security, and the still ignorant doctors. Do not wait, take precautions before waiting for baby. Provide yourselves with all the necessary news from the doctors, don’t be afraid to ask them if they are competent to look after you or not ( ... ) And above all, speak with your mother (if you can do it), don’t be scared of asking her the questions which bother you. You have to fight and to stick together.
A fit of rage, because at present I’m fighting against the administrations to claim to the right to a help ( ... ) Distilbène pregnancy is not recognized as a " highly pathological " pregnancy and it has to change. We have to find means in a spirit of solidarity, to have, at last, the right to the recognition of our health. "

" ( … ) between 1958 and 1962, I had five miscarriages. In brief, I did my best to have a baby... In the years 81/82, when I listened to the radio an information concerning the ravages of Distilbène, I immediately warned my children (her daughter had to suffer from three miscarriages), so that we have quite open and frank relations. This subject is not a taboo between us. I do absolutely not feel guilty towards my daughter and her three lost babies ( ... )
Here is my history. Today I am in mourning for my grand children. "

" (... ) I lost it during the 23-rd week of pregnancy ( ... ) Beyond the very big pain to have lost my child ,I was deeply shocked by the silence which surrounds the loss of a " child to be born " which is not recognized. The medical profession shies away from this suffering ( ... ) The mourning of this child, it is a mourning without any mourning, just like the families of wrecked sailors whose bodies were not found: this is a real loss but rituals are missing... "

" ( … ) Only one year ago, further to all these failures, we were completely desperate (several pregnancy terminations, numerous treatments.) but we didn’t give up. Remaining confined to bed during seven months is not easy. It requires a lot of patience, understanding from the confined woman, but also from her family and friends circle. Moments of fear, crying fits... It is necessary to remain optimistic … "

" My daughter was born on 22.11.98. I can speak about the psychological horror lived until the past term of the big prematurity ( ... ) The most difficult is also the collective lack of understanding (friends, close relations) " you see, everything wen off smoothly "," you see, you are pregnant although you thought it was impossible, it is not so bad!!! " I needed to protect myself. Many thanks to the newspaper for existing, since it is a fundamental landmark and place to express an underestimated and often misunderstood pain. "

" On the day she was 36, my daughter announced us she was waiting for a baby. Such a miracle! Our common gynecologist always laughed at us because of my anxiety: " I was reading too many newspapers ". he said
At the hospital, the first reaction of the obstetrician during the examination: " did your mother take distilbène during her pregnancy? " ( ... ) He told her that because of her very tiny womb, it was necessary to rest sixteen hours a day to avoid the opening of the cervix ( ... )
I have a grudge against my gynecologist who had a radio of the womb of my daughter for several years and who has laughed at me for about 15 years. "

Hélène met numerous specialists to treat her primary infertility, which she has for her part always attributed to the D.E.S. She speaks about the doctors she met, who propose her treatments without taking into account questions she asks about Distilbène : " I feel their irritation against the slightest questions, they are reluctant to give me the results ( ... ) I am a nurse and now they blames me for " seeing my case with nurse's eyes "!!? "

" In 1993, I learnt what was the D.E.S. thanks to the gynaecologist who followed me at that moment. He was about the 4-th I met (among which the one that had looked after my mother at that time and that followed her from 91 to 92 before retiring without informing her). Why did he remain silent, did he feel guilty ? And did he forget me? I have the right to know, it is my life, our desire for child ( ... ) The doctors should take their responsibilities and should talk, they should stop thinking that people in front of them don’t understand anything. "

" (... ) I also received the bulletins of the Association, and I find it great to gather the testimonies of concerned persons, or the opinion of competent doctors. Since I read your bulletins and the explicative brochure, I feel almost reassured. I’m reassured to see that I am not alone because in the Lebanon, nobody speaks " about that " … At last, I can have an answer to my fears, I’m informed about the experiences lived by the others. Your " pink pad " is a great hope! Because it is necessary to be positive and to keep hope and you’ve better being informed! ( ... ) "