Pregnancy outcome in women exposed to DES in utero, their mothers, and unexposed siblings

Pregnancy Outcome in 98 Women Exposed to Diethylstilbestrol In Utero.

Abstract

Pregnancy Outcome in 98 Women Exposed to Diethylstilbestrol In Utero, Their Mothers, and Unexposed Siblings, Obstetrics and gynecology, Volume 59 – Issue 3, July 1981.

The reproductive capability and labor complications of 98 women exposed to diethylstilbestrol (DES) in utero were compared with those of three separate control groups. The controls consisted of:

  1. 167 age-matched, normal women,
  2. 20 siblings not exposed to DES who had achieved pregnancy,
  3. and their mothers.

Spontaneous abortion, ectopic pregnancy, incompetent cervix, and premature labor occurred significantly more often in the DES-exposed population than in the normal controls.

The controls also achieved a higher percentage of desired pregnancies overall; this was statistically significant (89.6 versus 75.0%, P less than .001).

When compared with their mothers, however, the DES-exposed population achieved a greater percentage of desired, viable pregnancies (75.6 versus 67.0%, P less than .001).

The unexposed siblings of the DES women achieved a higher percentage of desired, viable pregnancies than did their exposed sisters (86.9 versus 73.6%, P = .274), but less than the normal population (86.9 versus 89.6%).

Click to download the full study.

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Pregnancy outcome in women exposed to diethylstilbestrol in utero

image of pregnant-woman
The outcomes of the pregnancies of DES-exposed women registered in the Stilbestrol Clinic at the Stanford University Medical Center were examined in 1981. Pregnant Woman.

Abstract

American journal of obstetrics and gynecology, NCBI PubMed PMID:7234915, 1981 May.

The presence of anomalies in vagina, cervix, and uterine body of women exposed to diethylstilbestrol in utero has provoked interest and concern regarding the reproductive potential of these women. To expand and to evaluate better better the current knowledge in this matter, the outcomes of the pregnancies of exposed women registered in the Stilbestrol Clinic at the Stanford University Medical Center were examined.

The results were combined with the published results of similar examinations of other institutions and a summation of all available data is presented.

  • Although it is evident that the majority (79%) of exposed women who have become pregnant and not regularly sought abortion have obtained at least one living infant, the incidence of spontaneous abortion and preterm delivery has consistently been found to be greater in exposed women than in unexposed control women.
  • One of every 30 pregnancies reported in exposed patients has been ectopically located.
  • Additionally, there is suggestive evidence that exposed women with teratologic changes have a higher incidence of pregnancy loss than those without such changes.

However, few of these observations can boast statistical validity and statistical validation of the same observation by separate investigators has not been obtained. Moreover, none of the teratologic changes in exposed patients has been seen to preclude normal pregnancy and term delivery.

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Reproductive performance of DES-exposed female progeny

image of empty-couffin
This 1981 study showed that fetal wastage is high in DES Daughters.

Abstract

Obstetrics and gynecology, Volume 58 – Issue 1, July 1981.

The reproductive performance of 106 patients exposed in utero to diethylstilbestrol by maternal ingestion is described.

Fetal wastage is high, apparently because of spontaneous abortion during the first and second trimesters.

Recommendations – see image below – are made for preconception counseling of exposed progeny to increase fetal salvage.

Obstetrics and gynecology, Volume 58 – Issue 1, July 1981.

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Reproductive Outcome of Women exposed to Diethylstilbestrol In Utero

image of dark-candle
In this 1980 survey, among pregnancies that progressed beyond 20 weeks’ gestation, the incidence of premature delivery was significantly increased and associated with an increased perinatal mortality. Those risks are even bigger for DES Daughters with gross cervicovaginal changes. dark candle light.

Abstract

Obstetrics and gynecology, Volume 56 – Issue 1, July 1980.

Diethylstilbestrol DES exposure in utero produces histologic and gross anatomic abnormalities in the lower and upper female genital tract. The authors investigated the reproductive history of 71 DES-exposed women by comparing their questionnaire data with those of 69 demographically matched non-DES-exposed control subjects.

  • The study group’s menstrual indices were comparable with those of the control group except in menstrual flow, which was significantly shorter in duration (P < .001), and in dysmenorrhea, which was reported more often (P<.05).
  • Fertility, as indicated by incidence of pregnancy, mean gravidity, and frequency of infertility problems, did not differ between groups.
  • The incidence of early (less than 20 weeks) pregnancy complications, ectopic pregnancy, and spontaneous abortion was comparable between groups. However, the incidence of late (after 20 weeks) pregnancy complications, premature delivery (40%, P<.001), and perinatal death (25%, P<.05) was significantly increased in the study group. Among DES-exposed subjects with gross cervicovaginal changes, premature delivery was even more frequent (71.4%, P<.0005), and consequently it was associated with a higher perinatal mortality (43%, P<.001).

The authors conclude that DES exposure in utero in this study group was not associated with increased difficulty in conceiving or early pregnancy complications. However, among pregnancies that progressed beyond 20 weeks’ gestation, the incidence of premature delivery was significantly increased and associated with an increased perinatal mortality. The mechanism(s) for these premature deliveries remains to be elucidated.

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Reproductive problems in the DES-exposed female

image of pregnancy
Reproductive problems in the DES-exposed female, 1980 findings. Pregnant-25-weeks.

Abstract

Obstetrics and gynecology, NCBI PubMed, PMID:7366902, 1980 Apr.

The records of 25 diethylstilbestrol-exposed women under treatment for reproductive dysfunction were reviewed.

A tendency toward:

  • pregnancy wastage (5 of 10 patients),
  • ectopic pregnancy (2 of 8 patients),
  • cervical factor infertility (15 of 20 patients),
  • hysterographic abnormalities (15 of 19 patients),
  • and ovulatory dysfunction (10 of 25 patients) was noted.

With the exceptions of ovulation induction and cervical cerclage, no means of treatment can be recommended.

Click to download the full study.

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Comparison of Pregnancy Experience in DES-Daughters and unexposed Women

pregnant image
In this 1980 study, the difference in pregnancy outcomes between the DES daughters and the unexposed is highly significant. Pregnant.

Abstract

A comparison of pregnancy experience in DES-exposed and DES-unexposed daughters

The Journal of reproductive medicine, NCBI PubMed,  PMID:7359503, 1980 Feb.

Reproductive histories were compared for 226 DES-exposed and 203 -unexposed daughters whose mothers participated in a double-blind evaluation 27 years before.

  • Irregular menstruation was slightly more common among the exposed (10%) than among the unexposed (4%).
  • Nineteen of the exposed and only four of the unexposed had primary infertility.
  • Among those at risk, 86% of the unexposed and 67% of the exposed had become pregnant. The reasons for these differences are not known.
  • Comparison of evaluable first pregnancy outcome revealed full-term live birth to be more common among the unexposed (85%) than the exposed (47%).
  • Premature live birth was experienced by 22% of the exposed but only 7% of the unexposed.
  • Nonviable outcomes of stillbirth, neonatal death, miscarriage and ectopic pregnancy occurred in 31% of the exposed and 8% of the unexposed.

The difference in pregnancy outcomes between the groups is highly significant. The DES-exposed with transverse cervicovaginal ridges were more likely to experience a nonviable outcome. Overall 82% of the exposed and 93% of the unexposed had at least one live offspring.

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DES Daughters

What is a DES Daughter? Who are they?

DES Daughters are all the women born between 1938 and 1978 who have been exposed in utero to the anti miscarriage drug and man-made estrogen Diethylstilbestrol (or DES in short) Diethylstilbestrol DES Google+ Page icon.

They live in the U.S.A., Canada, Australia, Europe and all corners of the world where the drug was prescribed decades ago during pregnancy.

DES Daughters during a DES Symposium image
DES Daughters during the MGH Boston 2011 DES Symposium – Andrea Goldstein, Caitlin McCarthy, Cheryl Roth.

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.

Sources:

  • DES Action USA Voice newsletter spring 2005
  • DES Action USA
  • Viva Presse.fr
  • M6Bonus.fr
  • Hhorages.

Notes:

*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).