Repercussions of distilbene in the children exposed in utéro

OF or diéthylstilbestrol is a Oestrogène of synthesis (the first with being able to be managed by oral way) which was marketed under the name of Distilbène® or StillbestrolBorne® between the years 1950 and 1977 in France (first marketing in Belgium and Switzerland in 1948). In spite of the fact that, very quickly (since 1953), of the studies showed the inefficiency of this molecule, nothing could stop the world passion for this new drug, which became considerable extensive. Was managed it mainly to prevent occurred of miscarriages, but very quickly, his indications extended to the treatment from sterility, the diabetes gestationnel, pre-eclampsia… Its peak of use is located between the end of the year 1960 and the beginning of the year 1970. It is in 1971, following the discovery of the first case of ascribable cancer with, that the latter was interdict in the United States. It is only into 1977 that this same decision was made in France. Today, Distilbène® is still prescribed, but only within the framework of the treatment of the cancer of the prostate at the man.

It is at present that the problem of is felt more. Indeed, this drug proved to be, a posteriori , harmful for the children exposed in utéro to this molecule (mainly for the girls). It is in particular responsible for genital anomalies in these exposed children.

One estimates at 200.000 the number of women having received in France between 1950 and 1977.

The number of children exposed in utéro is estimated at 160.000 (80.000 girls and 80.000 boys).

Consequences of distilbene in the exposed girls

anatomical Anomalies of the genital ways:

They can be absent, isolated or multiple (all the more frequent as the embryo was precociously exposed with the molecule).

adénose cervicovaginal : presence of fragments of uterine mucous membrane on the level of the vaginal wall and the cervix. Most of the time, these lesions are asymptomatic, but they can also cause abnormal vaginal discharge, even bleedings (rare). These anomalies are nevertheless to supervise narrowly because of the risk of abnormal transformation of these cells (dysplasy). They thus impose an annual smear, as of adolescence.
contracting of the uterine cavity (uterine hypoplasy) or uterus in form of T which generate difficulties of nidation and an increased risk of miscarriages. Among certain women, malformations are such as no pregnancy can be hoped.
abnormal opening of the collar (gaping of the collar) explaining the increased risk of late miscarriages and infections.
horns hails , even, in certain cases, completely stopped.

Turbid of the fertility:

They meet at 1/3 of the exposed women, which corresponds at the risk doubled compared to the general population.

One can observe among these women:

of the anomalies of the cervical glaire preventing the passage of the spermatozoa beyond the cervix.
of the disorders of ovulation, going until the complete absence of ovulation (anovulation).

Complications at the time of the pregnancies:

In the event of pregnancy, these women present an increased risk:

of miscarriages with repetition.
of late miscarriages, because of the gaping of the uterine collar.
of extra-uterine pregnancies (risk multiplied by 6).
of threats of premature birth (contraction well before DPA, requiring rest and a treatment)
of prematurity.

Cancer of the vagina and the cervix:

This type of cancer remains rather rare (1 woman out of 1000 exposed women). It appears especially between the ages of 17 and 22 years, but cases were described up to 30 years. One must think of it, in the event of abnormal bleedings apart from the rules among these women. This cancer all the more has chances to answer well the surgery and the radiotherapy, that the diagnosis is made precociously. It is thus important that these women are followed once per annum by a gynecologist, with smear of the vagina and the coll. Any abnormal bleeding must also impose a fast gynaecological examination, in order to exclude this possibility.

Psychiatric disorders:

Certain studies tend to show that certain serious psychiatric disorders concerning these children exposed and appearing with post-adolescence (schizophrenia, disorders of the food behavior, depressions serious) could be the consequence of the impregnation of the mothers by OF during the pregnancy. Other studies are nevertheless still necessary to confirm or cancel these results.

It should nevertheless be noted that a certain number of girls whose mothers took during the pregnancy will not have any difficulty of having children, and will present neither diseases, nor malformations.

Girls OF and sterility:

In case dabsence of pregnancy among these women, it would be necessary to realize:

a normal assessment of hypofertility
a test of Hünher
a hysterography to detect anomalies of the uterine cavity and horns.
an echography with Döppler of the uterine vessels, in order to evaluate the uterine perfusion.

Certain important malformations can profit from the surgery and it is necessary to treat the other independent factors being able to influence sterility.

All the techniques of LDC can be considered:

the stimulation of ovulation can help in the event of dysovulation
artificial insemination can be beneficial when there exists an anomaly of the cervical glaire.
the FIV is a good option when the horns are stopped.

Moreover, one systematic search for exposure to should be realized at any woman presenting of the disorders of the fertility, the GEU, the FC early or late, and whose age leaves suspecter a risk of exposure.

And in the event of pregnancy?

Although the majority of the pregnancies proceed normally among these women, these pregnancies must nevertheless be regarded as being " with risque" (comparable with that of the twin pregnancies).

According to the obstétricaux antecedents, uterine malformations and state of the collar, certain precautionary measures can be taken: - the rest makes it possible to prevent to them miscarriages and prematurity - a hooping of the uterine collar will be necessary in the event of gaping of the collar

And the Distilbène wire?

The consequences of the exposure in utéro to are well-known at the woman. Well few studies were carried out at the man. Can one conclude from it that this drug does not assign the boys? Nothing is less sure.

The studies are, certainly, still very few and so base themselves only on few data. Moreover, they remain prone to controversy, at present.

But why the effects at the man are if not very known? The consequences would not be as specific as at the woman, nor also low registers.

One notes mainly:

of minor malformations of the male urogenital system: not descended testicles (cryptorchidie) and badly closed urethra (hypospade), in particular.
the effect of on quality of the spermatozoa remains largely discussed. Certain studies showing a light hypofertility, but no sterility could be charged to this drug.
One would also observe an increase moderate in the frequency of cancers testiculaires at these wire distilbene, imposing an special attention on tracking at these men?

Additional studies are still necessary, at present, to cancel or confirm these results. One estimates at 80.000 the number of boys exposed to distilbene, in France.

According to a Dutch study, these malformations can affect the 3rd generation. Trans-générationnelles studies are in hand.

Source

Natisens site on procreation médicalement assistée
Distilbène

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