Neurodevelopmental disorders in children exposed in utero to synthetic progestins

Analysis from the national cohort of the Hhorages Association, 2018


The medical and scientific communities have not yet fully acknowledged the undesirable effects of the synthetic hormones that have been administered to pregnant women for decades.

The somatic effects of in utero exposure to diethylstilbestrol (DES), such as genital malformations, infertility, and cancer, have long been recognized but this has not been the case concerning psychiatric disorders.

The progestins used in contraception and hormone replacement therapy are known to affect the adult brain, but no data exist on their effects due to in utero exposure of children.

The Hhorages Association, a national patient support group, has assembled a cohort of 1200 women who took synthetic hormones during pregnancy.

These women had a combined 1934 children. We obtained full questionnaire responses from 46 women treated with progestins only – and not an estrogenic cocktail – who gave birth to 115 children.

Three groups were observed:

  1. Group 1 (n = 18): firstborn unexposed children,
  2. Group 2 (n = 62): children exposed in utero to synthetic progestins,
  3. and Group 3 (n = 35): children born after a previous pregnancy treated with progestins.

No psychiatric disorders were reported in Group 1 and the incidence of psychiatric disorders was drastically elevated in Group 2.

Our work shows a striking increase in psychiatric disorders among children exposed in utero to progestins and strongly suggests that prenatal exposure is associated with a high risk of psychiatric disorders in adolescence and adulthood, whether accompanied or not by disorders of sex development.


  • Neurodevelopmental disorders in children exposed in utero to synthetic progestins: analysis from the national cohort of the Hhorages Association, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, DOI: 10.5772/intechopen.80969, November 5th 2018.
  • Image credit Alexander Krivitskiy.

Evidence for Link Between Mental Disorders and in Utero Exposure to Synthetic Hormones

A Long and Crucial History, IntechOpen, 2018


Somatic effects of diethylstilbestrol on children exposed in utero have long been recognized. This is not the case for psychiatric disorders, although animal studies provide evidence of somatic and behavioral disorders.

Recent studies have reported psychiatric effects of synthetic estrogens on the brain of children exposed in utero as schizophrenia, bipolar disorders, depression, eating disorders, suicides, suicide attempts. Recently, a team of St. Anne’s Hospital, Paris (Prof. Krebs, Dr. Kebir) demonstrated the epigenetic mechanism of DES effect on the brain, a specific methylation of two genes playing important roles in neurodevelopment: the ADAM TS9 (control of the formation of reproductive organs and of the fetus’s CNS) and the ZFP 57 gene suggested to be associated with psychosis.

Progestins used in contraception and in hormone replacement therapy are known to affect the adult brain, but no data on children existed before our recent paper on their effects after in utero exposure. Clinical data were collected from 1934 children of the Association of Patients HHORAGES cohort.

Our data show the presence of somatic disorders and a drastic increase of psychiatric disorders among children in utero exposed to progestins. These mental disorders are the same as pathologies provoked by exposure to synthetic estrogens.


At the end of the 1990s, somewhere in France, an agricultural engineer, Mr. RA, made the observation that his three children were suffering from various psychic and somatic pathologies, the elder suffering from bilateral cryptorchidism, micropenis, infertility due to azoospermia (no spermatozoa), and schizotypal character; the second from anxiety, depression, and eating disorders (anorexia) coupled with small uterus and ovaries; and the third suffering from schizophrenia and severe depression associated with suicide attempts. He observed also the relationship with the fact that in all three cases, his wife received medical treatment consisting of a synthetic hormone cocktail: diethylstilbestrol (DES), ethinyl estradiol (EE), plus synthetic progestin delay during her three pregnancies after a previous miscarriage. He conducted research in the world literature on the subject and came to the conclusion that not only was one of these products, diethylstilbestrol (DES), already known for its misdeeds but that it continued to be administered in France until 1977/1982. The product, inexpensive to make, was not patented and was manufactured and distributed by many pharmaceutical laboratories. The same goes for EE, which was banned for pregnant women in 1980 but remains the best-selling estrogen in the world because it is part of the contraceptive pill.

In 1998, one of us (MOS-G), concerned by the same kind of problems in her two children who were exposed in utero to the same cocktail of synthetic estrogens, lost her two children after psychiatric illnesses. Following the reading of a “Call to Families” printed in a newspaper, she met Mr. RA, who had gathered around him about 20 French families concerned with their in utero-exposed children suffering from psychiatric illnesses. He wanted to expose his observations and the results of his bibliographic researches at a meeting of patient families collecting observations on the genital malformations of girls exposed in utero to DES. Alas, he was condemned, rejected, and disclaimed by doctors, mostly gynecologists and psychiatrists as well as by associative members. They denied the existence of psychiatric disorders in exposed boys and girls. Discouraged, Mr. RA died shortly afterward. In order to continue his work and regroup the families concerned by the origin of the heavy psychiatric pathologies of their children and despite the taboo surrounding such diseases as psychoses, we gathered several mothers concerned and created the Association of Patients Halt to Artificial Hormones for Pregnancies (HHORAGES), in 2002. This Association which collected more than 1300 French spontaneous testimonies is now registered with the Epidemiology Portal of French National Institute for Medical Research (INSERM) as a French Health Database.

Despite various alerts published in the 1940s, after work on animals proving in particular its carcinogenic effect, and despite the work of Dieckman et al., initiated as early as 1953, demonstrating in a large cohort of pregnant women given diethylstilbetrol (DES), a synthetic estrogen, versus placebo that the drug was inefficient in preventing miscarriages or premature births, this product has been widely distributed around the world, sowing a long list of misdeeds. After the discovery of cervicovaginal cancers called “clear cells adenoma (CCAD)” in the “DES girls,” DES was banned in the United States for pregnant women in 1971 but only in 1977 in France, where this recommendation disappeared from the “French Vidal book,” but DES continued to be prescribed sporadically until 1982. Meanwhile another synthetic estrogen, steroidal, also synthesized on 1938, 17-alpha-ethinyl estradiol (EE), was often added to DES as a cocktail or later as a replacement, sometimes with the addition of synthetic-delay progestin. The idea that prevailed at the time was that women had a hormonal deficit that triggered a miscarriage, whereas now we know that the miscarriage itself causes this deficiency. These products were prescribed not only to women who had miscarriages but also in comfort (“to have beautiful babies,” according to an advertising) or even as a “morning after pill” or to cut milk after childbirth. DES and 17-alpha-EE, although belonging to different estrogenic and degrading categories, are, however, bound to the same ER beta-estrogen receptors.

Behavioral disorders demonstrated in animals (rats) exposed in utero

Animal studies (on mice and rats) have demonstrated the toxicity of these synthetic estrogens on the offspring, including the cause of behavioral disorders. Palanza et al. demonstrated in particular that prenatal exposure to three different synthetic chemicals, DES and two pesticides, DDT and methoxychlor, and its analog, affects the behavior of young suckling mice, showing increased aggression in males (increased numbers of attacks and decreased reaction time before the attack). Doses of DES were 1000 times less than those of DDT and caused much larger aggression responses, demonstrating the considerable effect of DES at very low doses. The treatment period for rodent mothers from day 11 to day 17 of pregnancy was also critical because it represents a key period in the differentiation of the reproductive system and brain development in these rodents in the early stages of pregnancy.

Moreover, injection of 17-alpha-estradiol (EE) in pregnant rats causes not only many abortions in mothers but also anxiety and depression disorders in offspring, the synthetic hormone having been administered at the same relative doses as in humans (15 g/kg, 1 per day, versus 19 g/kg, 1 per day). At the cytological level of the brain, an alteration of the anterior part of the hippocampus in young rats exposed to EE in utero has been demonstrated in 2004. The hippocampus is indeed a part of the brain that contains many estrogen receptors during the prenatal period. Ogiue-Ikeda et al. showed in 2008 that synaptic plasticity can be upset by estrogens or other endocrine disruptors (EDs). Later and unequivocally, Newbold demonstrated the validity of the rodent model transposed to humans.

Behavioral disorders, psychoses, and depression demonstrated in humans after in utero exposure to DES/EE

In humans, the work concerning the appearance of behavioral disorders in children after in utero exposure to synthetic hormones is less numerous, but as early as 1977, June Reinisch published in Nature that prenatal exposure to estrogen and/or synthetic progestins could affect the personality of exposed children. More recently, in 2012, Kebir and Krebs have analyzed several epidemiological studies concerning the effects of DES on exposed children in utero and the occurrence of psychiatric disorders in these children. Their analysis shows that only three large epidemiological studies on the effects of DES were performed in 1952–1953 (followed up in 1983), in 2007, and in 2010. The first study (double-blinded) that supports the hypothesis of a link between psychiatric disorders and prenatal exposure to DES was performed by Vessey et al., in 1983, from a clinical trial that had been performed 30 years earlier in 1953 in London by Dieckman et al., on 700 women treated with DES versus 700 subjected to a placebo. A doubling of depression and anxiety disorders has been demonstrated in the population exposed in utero. The second, published in 2007 and conducted by Verdoux et al., from a cohort of women from the Mutuelle (Health) de l’Education Nationale (MGEN) concludes that there are no significant links between exposure to DES, suicides, and/or psychiatric consultations or hospitalizations. A detailed analysis later, however, revealed a number of biases in this study. The most recent Nurses’ Health Study was conducted by O’Reilly et al., 2010, from 76,240 American women among whom 1612 women were exposed to DES in utero. The statistical analysis shows that the latter experienced an increase in depressive and anxiety disorders by a factor of 1.3. Kebir and Krebs emphasized the limitations of such epidemiological studies and noted in particular that, apart from depression and anxiety, other psychiatric disorders have not been studied. Postadolescence behavioral disturbances reported for these two estrogens in exposed children were depression, anxiety, schizophrenia-like behavior, anorexia, and bulimia nervosa. All these observations were synthesized by Pillard et al. and Giusti. On 1987, Katz et al. described the case of four male adults prenatally exposed to DES. It is in late adolescence that they develop psychotic disorders requiring neuroleptic treatment even though they have no family history of this type. He then hypothesizes that there may be a causal relationship between disruptions in neurodevelopment related to DES and the subsequent onset of psychotic disorders. Pillard et al. showed that the frequency of recurrent major depressive episodes is significantly higher in the DES-exposed than in their unexposed siblings, which was confirmed in 2010 in the large cohort of DES girls by O’Reilly et al.

Investigation of the causal link between exposure to these synthetic hormones in utero and severe psychotic disorders such as schizophrenia, bipolar disorders with or without eating disorders, and schizoaffective disorders, occurring in postadolescence in exposed children, was made possible thanks to the families of the Association HHORAGES. Our database, constituted by these spontaneous families’ testimonies, is based on responses to a detailed questionnaire, written by doctors and researchers and accepted by the CNIL (French Center for the Protection of Data Processing and Freedom). Our first global analysis (2004–2005 data) was based on 967 pregnancies from 470 mothers in collaboration between 2 of us (MOS-G/CS) of us (CS). The first results as well as the family questionnaires were detailed in 2012 in the chapter published in 2012 by InTech “Behavioral and Somatic Disorders in Children Exposed In Utero to Synthetic Hormones” in which we detailed somatic and psychiatric disorders, associated or not, in the exposed children of our cohort.

We have conducted a more recent analysis (2016) based on 1182 pregnancies from 529 mothers. Among the 740 (20 stillborn) exposed children, 603 (exposed) +16 post-DES (born without exposure but after a previous exposed pregnancy) are suffering from psychiatric disorders. The prevalence of the psychiatric disorders in comparison with the general population shows a dramatic increase.

We were also interested by the effects on the brain of synthetic progestins on in utero-exposed children of our cohort. Currently, there is no research on these effects of in utero exposure of children to progestins given alone during pregnancy. Our recent observations were collected from 1200 families of the HHORAGES cohort, that is, 1934 children using always the same detailed questionnaire. As previously shown, most families of our cohort had children exposed to estrogens or to estro-progestins, but only 46 families (115 children) had at least 1 child exposed to 1 or more progestins prescribed alone and representing 62 in utero-exposed children. Thirty-five children were post-exposed. The prescribed progestins were 17-α-hydroxyprogesterone caproate (synthetic progestin, SP) against total indication in 2000 but reauthorized in 2011, 17-α-hydroxyprogesterone heptanoate (SP) against total indication in 2002, and chlormadinone acetate (SP), derived from hydroxyprogesterone, against total indication in 1970.

Among the 62 exposed children (22 girls and 40 boys), 49 presented psychiatric disorders, 6 presented somatic disorders only, and 7 did not present any disorder. Only 1 post-exposed presented psychiatric disorder, while 34 other post-exposed did not present any disorder.

Among the 49 children affected by psychiatric disorders, 3 boys and 7 girls presented both somatic disorders in addition to psychiatric ones: boys (3), hypospadias (1), no urinary meatus (1), bilateral cryptorchidia, and sexual ambiguity (1) and girls (7), hormonal sterility (2), hirsutism and enuresis (1), enuresis (1), hirsutism (1), hermaphrodism (1, operated), and sexual ambiguity and tight urethra (1). Among the six exposed children suffering from somatic disorders “only,” we observed for boys (four) mega bilateral ureter (one grandchild), unilateral cryptorchidia (one), hypospadias with numerous interventions of reconstruction (one grandchild), and sexual ambiguity (one) and for girls (two) hormonal sterility (two).

A comparison of synthetic estrogen and progestin exposures for girls and boys demonstrates that psychiatric disorders were of the same nature for progestin exposure as those observed after exposure to synthetic estrogens, that is, behavioral disorders = 2, eating disorders = 2, schizophrenia = 29, depression, bipolar disorders = 16, suicides attempts = 7 series, and death = 1. The percentage of suicide attempts (11.29%) and death after suicide (1.6%) is proportionately lower after exposure to progestins than after exposure to synthetic estrogens.

An epigenetic mechanism

Search for the molecular basis of the causal link between in utero, exposure to synthetic hormones and the appearance of psychoses as schizophrenia or bipolar disorder in children exposed in utero, has been achieved thanks to the partnership that unites HHORAGES Patients’ Association with the INSERM team of molecular psychiatrist Pr. MO Krebs (St. Anne’s Hospital, Paris, France, UMR S 894), which began in 2007.

“It would have been ‘crazy’ to miss the problem posed by the Association Hhorages to establish a causal link between taking artificial hormone(s) during pregnancy and appearance of psychiatric disorders of the type psychotic in exposed children, because diethylstilbestrol (Distilbene® or DES) has been given over a limited period of time and people who have taken this molecule are still there to testify. This is a case study that should not be missed”

said Dr. Kebir (Center for Psychiatry and Neuroscience, UMR S 894), manager of these researches as part of the Krebs’ team.

First, to document in utero exposure to synthetic estrogens, Kebir and Krebs were able to analyze from our data a small number of family records that occurred in HHORAGES testimonies and studied a cohort of 472 exposed subjects. They account for 46.7% of mood disorders, 22.9% of psychotic disorders, 6.6% of anxiety disorders, 11% of eating disorders, and 12.7% of others, which confirms their previous observations published on 2009 and 2010 at the seventh and eighth Congress of the Encephalon in Paris on 43 exposed children highlighting clinical pictures with atypical associations.

Second, genetic and epigenetic analyses of HHORAGES siblings have shown in patients suffering from psychotic disorders and exposed in utero to DES and/or EE that this prenatal exposure is associated with epigenetic processes. Starting from the fact that psychiatric diseases develop from a brain dysfunction during neurodevelopment, and knowing that DES and EE are synthetic hormones (estrogens), endocrine disruptors, and confirming from the HHORAGES data numerous cases of heavy psychiatric disorders in children exposed, the Krebs’team in association with HHORAGES designed 10 years ago, in 2007, a research project Partnership Citizen Institution for Research and Innovation (PICRI), funded by the Ile de France Region, net by the French National REsearch Agency (ANR), that developed the hypothesis that the DES administered during pregnancies could be an environmental risk factor for the development of psychiatric disorders in impregnated children: the epigenome of the foetus could have been modified by in utero exposure to synthetic estrogens. The PICRI project was titled “Influence of hormonal treatments on brain development during pregnancy: study of phenotypic, behavioral and biological changes in informative families.” The families of HHORAGES were called to perform peripheral blood sampling after thorough questioning. Many families volunteered to participate in the research: 31 families were selected, satisfying the rigorous inclusion criteria desired. Many more families had come forward during this study, but they could not be included because the psychotic patient refused to come to St. Anne’s Hospital for blood sampling. In the selected families, total siblings were composed of first-born unexposed children, exposed children, and post-exposed children, with first-born unexposed serving as intrafamilial control. For the exploration of their epigenome, 485,000 cytosines by genome were studied and analyzed, representing an immense work. To complete this study, a cohort of young adolescents with relational, emotional, and social difficulties was followed for 6 months, some of whom had developed schizophrenic-type psychosis in these 6 months, although not exposed to DES. A comparison of their methylome, analyzed before and after the onset of the disease, was performed. In this study, authors reported a global methylation of the psychotic patient genome.

After the analysis of the whole methylome of the selected HHORAGES cohort, the team of Krebs-Kebir highlighted differential specific methylated regions (DMR): in the zinc finger protein 57 gene ZFP57 and in the ADAM TS9gene and in young psychotic patients exposed in utero to DES/EE. In this work, the authors observed that in exposed individuals, ZFP57 gene methylation may be associated with their psychosis. The ZFP57 gene (located on chromosome 6) is expressed very early in development. It is a transcription regulator, directly related to the phenomenon of methylation and neurodevelopment. The ADAM TS9 gene is implicated in the control of organ shape, especially in the development and function of the uterus and reproductive organs which are often abnormal after in utero DES exposure as well as in the control of the CNS development and in several kinds of cancers.

Discussion and conclusion

Very few studies have investigated the impact of prenatal exposure to DES and EE on psychiatric outcome. Animal studies on rats or mice allowed us to hypothesize that estrogenic hormones induce neurodevelopmental disturbances in exposed human subjects and may potentially mediate an increased risk of behavioral and psychiatric disorders. Our data therefore strongly suggest that DES/EE exposure during pregnancy is associated with high incidence of behavioral and/or psychiatric disorders. They illustrate a higher risk of schizophrenia, as this disease was 17 times more prevalent than in the general population, with sons being more affected than DES daughters. Regarding the existence of eating disorders (bulimia, anorexia), it should be noted that girls are much more affected than boys, and we often observed the association of eating disorders with bipolarity (manic-depressive disorders), anxiety, and depression. With regard to suicides, our work clearly demonstrates a drastically increased risk of suicide attempts (65.4% versus 0 in the unexposed controls and 0.25% in the general population) and suicides (3.4% versus 0 in the unexposed controls and 0.02% in the general population). It could be noted that, as in the general population, DES sons commit more suicides than DES daughters and the inverse for suicide attempts. Moreover, our data reveal that 50% of the sons who committed suicide suffered from schizophrenia. Psychiatric studies in general have shown that the percentage of suicides is generally higher in individuals with psychiatric disorders than in the general population. But to our knowledge, there is no information or specific studies concerning this association in the context of DES exposure. Sixteen subjects in Group 3 (post-DES children) had diagnosed psychiatric disorders. An explanation for this finding might be that DES, being a very lipophilic synthetic estrogen, remains in the mothers’ fat after estrogenic impregnation in a previous pregnancy and is then released through the placental barrier during the next gestation.

No work had been reported on the impact of in utero exposure to synthetic progestin hormones administered alone on the occurrence of psychiatric disorders in exposed children before our first presentation in the European Congress of Gynecology in 2017. For the first time, we described psychiatric disorders that can affect children exposed in utero to progestins. Previously, and during many years, synthetic progestogens were not considered as dangerous during pregnancy or during replacement or contraceptive treatment. Moreover, they have been suggested to exert neuroprotective effects in several animal models of neurological disease. Negative mood symptoms have been reported by Andreen et al. in some women as a result of progesterone during the luteal phase of menstrual cycles. This is believed to be mediated via the action of allopregnanolone on the GABA-A system. A reduction of allopregnanolone circulating levels that correlates to depressive symptoms has been recently reported, and conversely, healthy women reported increased anxiety and mood disorders after long-acting subdermal implant of progestogens. In a group of 236 schizophrenic patients at onset, an elevated concentration of progesterone has been found, and authors suggested that steroid hormones may influence brain function, underlying schizophrenia, and major depressive disorders. Moreover, Buoli et al. (2016) found high DHAS levels in patients with a history of psychotic symptoms, suggesting a role of steroids in the etiology of psychosis and mood disorders. Progestins are known to induce GABA receptor activity/neural activation before birth; it is likely that a GABAergic system could contribute to schizophrenia, anxiety, depression, panic disorders, epilepsy, autism, and others. Although some progestins have been banned from the market, others are not: our data demonstrated that caution should be taken with regard to the use of these progestins during pregnancy and even outside these periods (contraception or hormone replacement therapy).

The brain is a very vulnerable organ because its development covers a very broad period extending from the early prenatal stage (third week of pregnancy) to end around the age of 20. During its development, there are times when its vulnerability is even greater than others; these periods are called “shooting windows,” during which the environment can impact the normal process of development. Abdolmaleky et al. as early as 2005 had developed the hypothesis that gene-environment modulations could be performed via DNA methylations. Krebs’ team put forward the hypothesis that DES-induced changes in epigenetic background and alteration of DNA functioning (methylations) could be significant factors to demonstrate a possible origin of psychotic disorders and a link with in utero DES exposure of the children suffering from these illnesses.

Numerous studies have shown that, for example, in the rat, early maternal separation or the fact of causing significant stress to the mother changes the methylation signals of certain genes of the rat directly related to the regulation of anxiety. It has also been discovered that the proper environment for changing the methylation signals may be chemical. This is the case of DES recognized by the scientific community as an endocrine disruptor and banned for pregnant women. This change in the level of methylation caused in utero by DES has been demonstrated for urogenital malformations of girls and boys as well as for cancers. On 2015, Harlid et al. published in a pioneer work the first study for evaluation of possible effects of in utero DES exposure on genome-wide DNA methylation in humans. They studied whole blood DNA methylation in 100 40–59-year-old women reporting in utero exposure, compared to 100 unexposed women. They did not find any differential methylation, but the DMR approach was not used in their recent work (2015). On the other hand, in 2017 Rivollier et al. described specific differential methylated regions (DMR) on two genes implicated in neurodevelopment (ZFP57 and ADAMTS9). Surprisingly, they cautiously claim that these DMR are “supposedly” associated with prenatal exposure to DES in young psychotic patients in utero exposed to DES/EE. Nevertheless, these modifications of methylation are really specific because they do not exist in the methylome of young psychotic patients not exposed to DES in which global methylation of the genome was observed. Moreover authors have compared exposed subjects to their unexposed siblings which do not present these specific methylations although they shared environmental and genetic factors.

The citizen work carried out between the French HHORAGES Patient Association and two major medical research laboratories has provided convincing scientific results: (1) on the detection and confirmation of the existence of psychiatric disorders (accompanied or not of somatic disorders) in children exposed in utero to synthetic hormones and (2) on the mechanisms of action of these synthetic hormones administered to pregnant mothers on the brain of their offspring. The effects of these endocrine disruptors in humans through what is becoming a public health scandal, denied for a long time by doctors, especially psychiatrists, scientists, and specialized journalists, are thus better known. The fact that these synthetic products do not degrade in the human body in the same way as the natural hormones and act on the functioning of genes implicated in neurodevelopment during the fetal life, following an epigenetic mechanism, is a real time bomb. Indeed, this mechanism induces a transgenerational effect already partially demonstrated in the HHORAGES cohort at the third-generation level for hypospadias, a specific genital malformation. So far, only a few third-generation children suffering psychiatric illness are documented in the HHORAGES testimonies. This is understandable because third-generation exposed children are still too young (excepted in some cases) to present psychiatric disorders as schizophrenia which is not the case for hypospadias that are detectable from birth in male children and grandchildren. In contrast, psychiatric disorders usually appear in postadolescence, 18–20 years, and sometimes later.

By Marie-Odile Soyer-Gobillard, Laura Gaspari and Charles Sultan,
Submitted: May 22nd 2018 – Reviewed: August 17th 2018 – Published: November 5th 2018.
© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


  • Full study free access) : “Evidence for Link Between Mental Disorders and in Utero Exposure to Synthetic Hormones: A Long and Crucial History, IntechOpen, DOI: 10.5772/intechopen.80969, November 5th 2018.
  • Image credit futurebrand.

New Online Global DES Health History Survey

image de connaissances

Calling all DES Mothers, Daughters and Sons!

DES diethylstilbestrol health history 2012 survey image
The DES Health History Global Survey is our chance to be heard and make all of our health experience counts!

Take part in the new DES Health History survey created by DES Action USA and open to all DES-exposed individuals worldwide.

The survey is designed to establish trends and identify health issues faced by women who took Diethylstilbestrol, their DES exposed children, and also their children (DES granddaughters and grandsons).

Data from the DES community on health conditions – beyond those already known – which appear more frequently in DES-exposed individuals than among unexposed populations is critically missing. This information is needed to share with researchers who can follow-up with further study.

My mum has recently been diagnosed with Hashimoto’s Thyroiditis, an autoimmune disease that affects the thyroid. Could it be associated with her exposure to Diethylstilbestrol back in the late 60’s? Is she the only woman who was prescribed the wonder drug DES during pregnancy to suffer from this health condition?

I suffer from anxiety and stress from worrying about what the future holds for my daughters and whether Diethylstilbestrol will affect their health and chances to give me and my husband grand children. Am I the only DES daughter out there who cries in secret when her little girl plays being a mum knowing that this synthetic hormone may one day prevent that imaginative play from becoming reality due to potential DES pregnancy complications?

The children of Marie-Odile Gobillard-Soyer, a French DES mother and researcher in molecular biology, both committed suicide. She started an association and in 2011 conducted a national study among children of French DES mothers which revealed a link between DES and mental illness issues in DES daughters and sons.  Could this be a worldwide trend?

In October 2011, the alarming results of a study analyzing the risks of diethylstilbestrol related disorders among women whose mothers took the synthetic hormone during pregnancy, compared to others who weren’t exposed were published in the prestigious New England Journal of Medicine. But victims of this drug scandal wonder if other health conditions that are currently not associated with DES by the medical profession could in fact be the direct result of Diethylstilbestrol exposure. Hopefully the new global DES Health History Survey will answer these questions.

Since I started my Journal of a DES Daughter, I’ve read many sad testimonials and DES stories. What they all share in common is the incertitude for the future and the feeling that the DES drug scandal and its associated health issues are not enough acknowledged publicly and by the medical profession. The DES Health History Survey will provide DES Actions groups and DES activists with the data needed to push for more studies and support for DES victims.

Why is it important to know whether your health condition is associated with DES or not? First because DES victims have the right to KNOW and more importantly because PREVENTION of these conditions when you know you are at higher risk can save lives.

The deadline for the completion and return of this survey is JUNE 15th 2012.

The survey can be completed online or you can download the “DES Health History Questionnaire“.

Please share this information on your social networks, with your friend and family who may be interested in completing the survey. I can’t stress enough the importance to take part! This is our chance to be heard and make all of our health experience counts!

French study reveals more damaging DES side effects

Diethylstilbestrol (Distilbène), the synthetic sex hormone prescribed in France up to 1977 (and in many other countries under different names) to pregnant women to prevent miscarriage and premature labour, has caused genital abnormalities, infertility problems, and cancer in children exposed in utero to the drug. A new report reveals that DES may have done even more damage, often associated in cocktail with other estrogens as 17-alpha Ethinyl oestradiol (synthetic EE) or with synthetic Progestin.

Distilbène® DES psychiatric disorders image
Click to watch the M6 Actu DES news in French

A disturbing study conducted since 2004 by Marie-Odile Soyer-Gobillard, former director emeritus at the CNRS (French National Center for Scientific Research) reveals a link between DES and mental illness issues. In January 2011, and next in October 2011, 6 members of the association Hhorages (Halt to Synthetic Hormones for Pregnancies), of which Marie-Odile is the president, were received by the AFFSSAPS (the equivalent of the Food and Drug Administration in the U.S. now named AFSM, French Agency for Medicament Security) to discuss her findings. A working group composed of experts from the agency and the association will now be formed in April.

DES Psychological Side Effects New French Stats

So what does the French study (published in the International Journal “Medicine and Longevity*) reveal? Marie-Odile sent questionnaires to 529 DES mothers and studied a group of 1180 children of which 740 have been exposed to DES in-utero. Of this group, 15 were still born and 684 suffer from psychiatric disorders and / or physical malformations while 41 were not ill. Amongst the studied population, the psychiatric illnesses are essentially depression, anorexia, schizophrenia, …). Today, Hhorages tots up 1223 testimonies representing 1223 mothers with a total amount of 2674 children. Amongst them, 1676 were in utero exposed to synthetic hormones, 1549 exposed children are ill: amongst them: 916 present psychic diseases « only », 448 present somatic and psychic diseases , 183 present somatic diseases « only »; 126 exposed are not ill. Amongst the observed siblings in the same family, only those who have not been exposed to DES in-utero, don’t show signs of psychiatric disorders …. Could this be just a coincidence?

Another shocking statistic: of all the cases reported since 2004, when the study started, Marie-Odile identified 150 suicide attempts series and 48 suicides. In some families, 2 or 3 children have ended their lives leaving their parents with a profound sense of guilt. Amongst the observed siblings in the same family, only those who have not been exposed to DES in-utero, don’t show signs of psychiatric disorders… Could this be just a coincidence?

Herself DES mother, Marie-Odile Soyer-Gobillard has been fighting since 1998 for the recognition of the link between synthetic sex hormones taken during her pregnancy including Distilbène®, and the psychological disorders of her own children, Nicolas and Valerie, who both committed suicide three years apart in 1995 and 1998 at age 28 and 27. She founded the association Hhorages with 3 other mothers in 2000 to raise awareness of the risks synthetic sex hormones prescribed during pregnancy pose on children born from these pregnancies.

According to Fran Howell (Executive Director DES Action USA), American researchers have been having trouble finding a solid link between DES and mental illness issues, except depression. But through the years DES Action USA have heard many reports of DES-exposed individuals suffering with psychological issues.

Pat Cody, co-founder of DES Action USA, wrote in the spring 2005 issue of VOICE (DES Action Newsletter) about why it is difficult for researchers to study these questions and develop definitive answers: “Here, some of the difficulties in getting a valid study are caused by a wide spread in the DES dosages mothers got, in the time in pregnancy when they got it, and for how long they took it (…). Sex hormones are, however, known to have effects on the organization of the brain in experimental animals with consequential behavioural effect”.

Distilbène® DES psychiatric disorders image
Click to watch the M6 Actu DES news in French

A 2005 study carried out by Professor Caston, a neurologist at the University of Rouen (France), has demonstrated that rats born to mothers treated with synthetic sex hormones developed anxiety and depressive behaviour. “These results could be explained by the effect of the molecule on the part of the brain involved in emotional processes, which is under development in foetuses”, the report says.

Could all the known DES side effects which have destroyed the lives of many DES mothers, daughters, and sons, just be the top of the iceberg? Already concerns for the grandchildren of DES mothers arise with a higher risk of hypospadias (misplaced opening of the penis) in sons of DES daughters. If more DES side effects are scientifically validated, DES could well be a real time bomb!

I welcome Marie-Odile’s research study and thank her and Hhorages for their combat and work on behalf of all the DES victims who suffer from the mental side effects of this drug.

More research is critically needed not only to provide DES-exposed individuals with appropriate care and support but for the next generation and all the people who may continue to suffer from the physical or mental consequences of this drug in the future. Please support Hhorages and your local DES Action group, and stay tune for more revelations about DES exposure and its devastating side effects.


  • DES Action USA Voice newsletter spring 2005
  • DES Action USA
  • Viva
  • Hhorages.


*Soyer-Gobillard, M.O. 2011. Endocrine disrupters and effects on behavioral disorders: No, we have not as yet learnt all our lessons concerning the DES story. Médecine et Longévité, (Elsevier Masson), 3, 67-74.
** Nicolas Kalfa, M.D., Ph.D,.Francoise Paris, M.D., Marie-Odile Soyer-Gobillard, Ph.D., Jean-Pierre Daures, M.D., Ph.D. and Charles Sultan, M.D., Ph.D. Prevalence of hypospadias in grandsons of women exposed to diethylstilbestrol during pregnancy: a multigenerational national cohort study. Fertil Steril, 2011, 95, 2574-2577(published by American Society for Reproductive Medicine).