Health effects : pregnancy use of diethylstilbestrol

The Journal of the Indiana State Medical Association, 1979

Abstract

The use of DES (diethylstilbestrol) to prevent pregnancy complications and miscarriages has shown effects in women who took DES and their offspring.

A University of Chicago follow-up study indicated that women who had used DES had more breast and gynecological cancers than a control group, although the results were statistically insignificant.

DES daughters have a higher occurrence of a rare malignant vaginal cancer, clear cell adenocarcinoma,

and DES-exposed males showed a history of cryptorchidism, hypoplastic testes, epididymal cysts, and low sperm counts.

A DES Task Force formed by the Office of the Assistant Secretary for Health in 1978 recommends that all persons exposed to DES be informed of health risks and that DES daughters be carefully monitored by using Pap smears, iodine staining, and colposcopy when necessary.

In addition, the Task Force recommends

  • that DES women not use estrogens,
  • that postmenopausal replacement estrogens be prescribed prudently,
  • that DES not be given to suppress lactation,
  • and that women given DES for postcoital contraception be informed of the possible health risks.

Sources

  • Health effects: pregnancy use of diethylstilbestrol, The Journal of the Indiana State Medical Association, NCBI PubMed, PMID: 458172, 1979 May.
DES DIETHYLSTILBESTROL RESOURCES

Physician advisory : health effects of the pregnancy use of diethylstilbestrol

Clinical toxicology, 1979

Abstract

A DES (diethylstilbestrol) Task Force formed in February by the Office of the Assistant Secretary for Health, examined the health effects of DES in pregnancy. This report is an outline of the Task Force’s recommendations.

Physicians should advise women to whom they prescribe the drugs of their exposure and of the need for follow-up medical care for themselves and their offspring. Physicians are also to provide patients inquiring of possible past DES exposure, complete and accurate information whenever possible, and such information should be provided free of charge.

The incidence of clear cell adenocarcinoma for DES-exposed daughters is between 1.4/100 to 1.4/10,000. Periodic examination, rather than active therapeutic intervention (e.g., surgery) is recommended for patients with adenosis. For asymptomatic DES daughters, periodic screening examinations should start at age 14 or at menarche; vaginal bleeding/discharge should be promptly evaluated. Hystersosalpingography should not be used as a routine screening procedure in DES daughters but should be reserved for cases of repeated pregnancy loss or infertility.

Asymptomatic DES mothers should have routine screening (e.g., annual pelvic exam including bimanual palpation and Pap smear; breast exam) appropriate for women with no prior estrogen exposure.

DES exposed males have been known to have:

  1. history of cryptochirdism;
  2. hypoplastic testes;
  3. epididymal cysts;
  4. and sperm abnormalities (low sperm counts, decreased motility).
    DES males should have physical examination, appropriate medical follow-up or corrective measures, as the case may be.

Use of DES postcoital contraception should be limited to situations where the fully informed patient or her physician deems that there is no alternative.

Sources

  • Induction of urogenital anomalies and some tumors in the progeny of mice receiving diethylstilbestrol during pregnancy, Clinical toxicology, NCBI PubMed, PMID: 37020, 1979 Mar.
  • Features image Michael Marusin
DES DIETHYLSTILBESTROL RESOURCES

Mise au point des connaissances en 2002

image de connaissances

Thesis, Walter-Kull Agnès, June 2002

Abstract

Le diéthylstilbestrol (Distilbène®) était le premier oestrogène de synthèse nonstéroïdien à apparaître sur le marché français en 1950. Son utilisation s’imposait d’abord aux USA à la suite des travaux menés par Smith dans le cadre de la prévention de certaines complications de la grossesse.

Après 25 ans d’utilisation, Herbst découvrait que le diéthylstilbestrol était responsable d’adénocarcinomes vaginaux à cellules claires chez les filles exposées in utero.

Après avoir retracé les principales étapes de « l’affaire Distilbène® » et rappelé les principales propriétés pharmacologiques de la molécule, l’ensemble des effets secondaires lié à l’utilisation du diéthylstilbestrol est abordé. Un cas clinique vient illustrer ces propos en exposant une malformation utérine (utérus en T) chez une jeune femme consultant pour stérilité secondaire et ayant été exposée au diéthylstilbestrol in utero. Une augmentation du risque de cancer du sein chez les mères traitées pendant leur grossesse est en outre rapporté ainsi qu’un nombre accru de malformations uro-génitales chez les garçons exposés in utero.

L’ensemble de ces données a amené le corps médical et paramédical à préconiser une prise en charge gynécologique, obstétricale et médico-psychologique de la population exposée. En 2002, soit 25 ans après l’interdiction de son utilisation chez la femme enceinte, de nouvelles données apparaissent et on parle pour la première fois d’une transmission transgénérationnelle des effets secondaires du médicament.

Sources

Le Distilbène DES, en savoir plus

Entre mère et fille, le DES, aspects psychologiques

image d'aspect psychologique

The psychological impact of DES exposure in women : a comparison of short-term and long-term effects in several generations of DES-exposed

2008 Study Abstract

Les aspects psychologiques liés à la prise du DES n’ont jusqu’ici que rarement fait l’objet d’études spécifiques. Ce sont principalement les équipes américaines qui ont fait des recherches dans ce domaine. Les auteurs se sont préoccupés essentiellement du vécu des femmes exposées in utero, de leurs réactions à l’annonce de cette exposition, et des conséquences qui en résultent : effets neurologiques, endocriniens qui peuvent entraîner des conséquences au développement intellectuel, psychique et sexuel de ces femmes ayant reçu du DES.

Ils concluent qu’il n’y a aucun effet du DES sur le plan cognitif. En revanche, il semblerait que sur le plan du comportement sexuel les femmes ayant reçu du DES in utero ont plus de difficultés dans leur vie sexuelle – “Psychosexual milestones in women prenatally exposed to diethylstilbestrol” – “Sexual activity level and sexual functioning in women prenatally exposed to diethylstilbestrol” – que les femmes du groupe témoin. De même, ils trouvent que ces femmes sont plus dépressives et montrent plus de difficultés psychologiques. Ils concluent que cette vulnérabilité psychologique est due à l’inquiétude consécutive aux problèmes gynécologiques et obstétricaux qu’elles rencontrent.

Par ailleurs, une équipe s’est plus particulièrement attachée à la recherche des effets psychiatriques sur le comportement humain des individus ayant reçu du distilbène in utero. Trois sur quatre jeunes adultes masculins psychotiques présentaient un électroencéphalogramme (EEG) perturbé. Tous les quatre avaient reçu du DES in utero. Les auteurs pensent que cette prérecherche est suffisamment significative pour qu’elle soit poursuivie. D’autres cliniciens se sont attachés à repérer quelle pourrait être la détresse des mères qui ont pris ce médicament. Ils ont rencontré des femmes qu’ils décrivent comme anxieuses, craintives et à la fois très mécontentes vis-à-vis du DES. Les plus âgées sont les plus atteintes.

Sources

  • Entre mère et fille, le DES, aspects psychologiques, Springer International Publishing AG, Le Distilbène® trente ans après, pp 83-91, février 2008.
  • Featured image Alex Blăjan.
DES DIETHYLSTILBESTROL RESOURCES

DES-Mother and DES-Daughter Relationship

Exposure to DES may reveal pre-existing difficulties from generation to generation

1996 Study Abstract

The psychological consequences resulting from the exposure to diethylstilbestrol (DES), a non-steroidal oestrogen, on the mother-daughter relationship are studied using semi-directive interviews with 43 daughters and 7 mothers treated with DES during their pregnancies.

Prenatal exposure to diethylstilbestrol and the mother-daughter relationship, US National Library of Medicine, European journal of obstetrics, gynecology, and reproductive biology, NCBI PubMed PMID: 8730622, 1996 Apr.

These women referred to gynaecological consultation for DES-related problems.

The daughters, exposed to DES during their foetal life, learned about DES after a pregnancy mishap (35% of the cases), or by accident (65% of the cases).

All of them were shocked when the existence of DES and its side effects were revealed to them.

Consequences on the mother-daughter relationship were

  • absent in 60% of the cases,
  • favourable in 20%,
  • and negative in 20%.

Five percent of the women showed hostility towards the medical practice, but 65% were not suspicious of the drugs administered to them during their pregnancies. For 64% of them, administration of DES to their mother had been kept secret. In 7 out of 50 cases, parents alone came for medical assistance in order to manage the secret.

Exposure to DES may reveal pre-existing difficulties not only between the mother and the daughter, but sometimes beyond from generation to generation.

More DES DiEthylStilbestrol Resources

DES mothers may manifest increased vulnerability to subsequent stresses in their lives

image of stress in woman

Vulnerability to stress among women with in utero diethylstilbestrol (DES) exposed children

Abstract

In utero exposure to diethylstilbestrol (DES) was initially linked to vaginal-cervical cancer and subsequently to reproductive difficulties. These unanticipated and ongoing health risks to female offspring may constitute a chronic source of stress for DES mothers.

Vulnerability to stress among women with in utero diethylstilbestrol (DES) exposed daughters, US National Library of Medicine, Journal of human stress, NCBI PubMed PMID: 3855173, 1985.

Image credit michaelclesle.

We interviewed 60 mothers of exposed daughters and 30 acquaintance controls. Two hypotheses were tested in regard to DES mothers: DES discovery and its aftermath have a direct, long-term, negative effect on psychological health and the DES experience intensifies the negative psychological effects of other adverse life circumstances.

To operationalize psychological health, we measured symptoms of “demoralization” and positive health practices–the latter as a behavioral indicator of mastery and personal control. We also measured adversities that may mediate the threat posed by DES, including stressful events, medical problems, and chronic burdens. We found DES history to be associated with poorer psychological health only when mothers encountered other losses and threats to themselves and their families.

We concluded that DES mothers may manifest increased vulnerability to subsequent stresses in their lives.

More DES DiEthylStilbestrol Resources

Observations on the psychological impact of diethylstilbestrol exposure and suggestions on management

Physicians can help the DES-exposed deal with their emotional issues

Abstract

The emotional impact of diethylstilbestrol (DES) exposure is described in a series of 50 mothers and daughters interviewed by psychiatrists. Patterns of response to this trauma and methods of resolution are discussed, and opportunities for preventive intervention by gynecologists are suggested. Specific, open dialogue about DES with the patient as a colleage can minimize the emotional sequelae of the experience.

PIP:

Observations on the psychological impact of diethylstilbestrol exposure and suggestions on management, US National Library of Medicine National Institutes of Health, The Journal of reproductive medicine, NCBI PubMed PMID: 7373597, 1980 Mar.

Image credit theloushe.

This study analyzes the emotional impact of diethylstilbestrol (DES) exposure in an index population consisting of 50 women at risk plus 30 mothers who were all interviewed about their DES experience in an open-ended, in-depth, clinical style. The findings show that significant emotional upset is the normal response to the knowledge that the ingestion of a drug during pregnancy can cause or has caused some abnormality in the offspring.

Nevertheless, the capacity of a woman to come to terms with the anxiety DES has generated, once she had been given the chance to express her feelings and fears, was impressive.

DES daughters reacted to the DES experience in one of 3 ways, in descending order of frequency:

  1. trust (80%). Most DES daughters rationalized that their mothers and doctors did the best they could, and were generally cooperative in their follow-up care;
  2. hostility (10%);
  3. and fear (10%).

90% of DES mothers came to terms with the knowledge and implications of DES exposure in ways characteristic of their life-long personality styles; in contrast, the remaining 10% who did not come to terms with the reality of DES exposure felt overwhelmed by quilt, paranoid rage, fear, and despair.

Physicians can help patients deal with such problems by:

  1. acknowledging problematical feelings and expecting them to be difficult to deal with;
  2. noting the patient’s pattern of response, and supporting her strengths;
  3. giving factural information matter-of-factly;
  4. listening to reactions to this information;
  5. giving a structured plan in which the woman participates and be available for follow-through on it (eg, periodic colposcopic examinations);
  6. and referring the women to support groups for an extended network of information and continued support.
More DES DiEthylStilbestrol Resources

Psychological Effects of Diethylstilbestrol Exposure

Guilt: the most common problem among DES mothers

Abstract

The psychological response of daughters and their mothers to discovery of in utero diethylstilbestrol (DES) exposure was studied.

At the DES Colposcopy Clinic, 41 daughters and 20 mothers were extensively interviewed. Twelve patients with abnormal cytology tests were controls.

Psychological effects of diethylstilbestrol exposure,  US National Library of Medicine National Institutes of Health,  JAMA, doi:10.1001/jama.1977.03270300056007, January 17, 1977.

Initial anxiety was usually followed by acceptance of the condition after examination and counseling. Patients responded best when informed of their problem by their mothers and when the relationship between mother and daughter was good.

The majority of patients found colposcopy to be unpleasant; they tended to be disturbed in proportion to the degree of being upset about DES exposure. The most common problem among mothers was guilt.

A questionnaire survey of physicians showed that they had less concern for psychological problems than patients or mothers did. Sensitivity and good communication on the part of medical personnel are recommended.

More DES DiEthylStilbestrol Resources

Osseous trabeculae and osteofibrosis as long-term effects of diethylstilbestrol

Abstract

In a study on the long-term effects of dietary diethylstilbestrol or 17 beta-estradiol on C3H mice, estrogens induced a proliferation of osseous trabeculae and increased the incidence and hastened the development of osteofibrotic areas in the sterna.

There were 6 osteosarcomas, 2 having metastases, in 1,242 mice fed dietary estrogens over 360 days, but none in 356 untreated controls.

Osseous changes and osteosacomas in mice continuously fed diets containing diethylstilbestrol or 17 beta-estradiol, Journal of the National Cancer Institute, NCBI PubMed PMID: 6944535, 1981 Sep.

These tumors were reviewed along with 4 early sternal osteosarcomas selected from 17 osteosarcomas (only 1 in a control) found thus in two other ongoing comparable studies.

In at least 1 case, and possibly in 2 other early cases, tumors were associated with areas of osteofibrosis, and 1 tumor was probably associated with proliferation of bony trabeculae in the medullary cavity.

More DES DiEthylStilbestrol Resources

Estrogen use to reduce the growth rate of tall girls

image of tall girl

Abstract

In the past 15 years 450 girls have been seen because of concern about tall stature: 168 of them have been treated with stilbestrol to control the growth rate. Of the latter group 87 have been followed after treatment for a sufficiently long time to be sure growth had ceased and to provide the data for this report.

At the onset of treatment the following data (mean values) were recorded: chronologic age, 13.0 years; skeletal age, 13.2 years; height, 172.9 cm; estimated mature height 180.2 cm; and growth potential, 7.3 cm. At the end of treatment data of interest (mean values) were: reduction in final height, 3.5 cm; duration of therapy, 2.1 years; amount of stilbestrol given, 2.3 gm; age of last visit, 17.6 years.

Tall girls: a survey of 15 years of management and treatment, The Journal of pediatrics, NCBI PubMed PMID: 165277, 1975 Apr.

Side effects were minimal, though two girls developed parovarian cysts that required surgery during treatment. Not included in the series of 87, one additional girl was seen with a serous cystadenoma of the ovary, and one girl developed superficial venous thrombosis of the calf. Long-term follow-up has revealed no late complications.

It is concluded that estrogen can reduce significantly the growth rate of almost all tall girls, but treatment must be carried out under very careful supervision, bearing in mind possible side effects.

More DES DiEthylStilbestrol Resources