Breast Cancer Risk in DES Mothers

Breast cancer in mothers given diethylstilbestrol in pregnancy

1984 Study Abstract

We compared the incidence of breast cancer in 3033 women who had taken diethylstilbestrol (DES) in pregnancy during the period from 1940 to 1960 with the incidence in a comparable group of unexposed parous women. We ascertained vital status in 95 per cent of the exposed women and in 93 per cent of the unexposed women and received completed questionnaires for 88 and 85 per cent, respectively.

With over 85,000 woman-years of follow-up in each group, the incidence of breast cancer per 100,000 woman-years was 134 in the exposed group and 93 in the unexposed group, yielding a crude relative risk of 1.4 (95 per cent confidence interval, 1.1 to 1.9). The elevated incidence did not appear to be due to bias or to confounding by other risk factors measured in the study.

Breast-cancer mortality was slightly higher in the exposed women (relative risk, 1.1) but not significantly so (95 per cent confidence interval, 0.7 to 2.0). We conclude that the incidence of breast cancer is moderately increased in women given DES, but we cannot exclude the possibility that some unrecognized concomitant of DES exposure accounts for this increase.

Public Information Programme

The authors compared the incidence of breast cancer in 3033 women who had taken diethylstilbestrol (DES) in pregnancy during the period 1940-60 with the incidence in a comparable group of unexposed parous women. The vital status was ascertained in 95% of the exposed women and in 93% of the unexposed women and completed questionnaires were received for 88 and 85% respectively. With over 85,000 women-years of follow-up in each group, the incidence of breast cancer/100,000 woman-years was 134 in the exposed group and 93 in the unexposed group, yielding a crude relative risk of 1.4 (95% confidence interval, 1.1-1.9). The elevated incidence did not appear to be due to bias or to confounding by other risk factors measured in the study. Breast cancer mortality was slightly higher in the exposed women (relative risk, 1.1) but not significantly so (95% confidence interval, 0.7-2.0). The incidence of breast cancer is moderately increased in women given DES, but the possibility cannot be excluded that some unrecognized concomitant of DES exposure accounts for this increase.

Sources

  • Breast cancer in mothers given diethylstilbestrol in pregnancy, The New England journal of medicine, NCBI PubMed PMID: 6493300, 1984 Nov 29.
  • Featured image credit Alisa Olaivar.
DES DIETHYLSTILBESTROL RESOURCES

DES Mothers and Breast Cancer Risk

Long-term cancer risk in women given diethylstilbestrol (DES) during pregnancy

2001 Study Abstract

From 1940 through the 1960s, diethylstilbestrol (DES), a synthetic oestrogen, was given to pregnant women to prevent pregnancy complications and losses. Subsequent studies showed increased risks of reproductive tract abnormalities, particularly vaginal adenocarcinoma, in exposed daughters.

An increased risk of breast cancer in the DES-exposed mothers was also found in some studies. In this report, we present further follow-up and a combined analysis of two cohorts of women who were exposed to DES during pregnancy.

The purpose of our study was to evaluate maternal DES exposure in relation to risk of cancer, particularly tumours with a hormonal aetiology. DES exposure status was determined by a review of medical records of the Mothers Study cohort or clinical trial records of the Dieckmann Study. Poisson regression analyses were used to estimate relative risks (RR) and 95% confidence intervals (CI) for the relationship between DES and cancer occurrence.

The study results demonstrated a modest association between DES exposure and breast cancer risk, RR = 1.27 (95% CI = 1.07-1.52). The increased risk was not exacerbated by a family history of breast cancer, or by use of oral contraceptives or hormone replacement therapy. We found no evidence that DES was associated with risk of ovarian, endometrial or other cancer.

Sources

  • Read the full paper (free access) : Long-term cancer risk in women given diethylstilbestrol (DES) during pregnancy, British Journal of Cancer, NCBI PubMed, PMC2363605, 2001.
  • Featured image credit Debora Cardenas.
DES DIETHYLSTILBESTROL RESOURCES

Breast Cancer in DES Mothers

Breast cancer in mothers prescribed diethylstilbestrol in pregnancy. Further follow-up, 1993

Study Abstract

Objective
Further assessment of the long-term risk of breast cancer associated with diethylstilbestrol (DES) during pregnancy.

Design
Follow-up continuation through June 1, 1989, of a historical cohort of DES-exposed and unexposed mothers ascertained by review of obstetric records.

Participants
Totals of 3029 each of DES-exposed and unexposed mothers who had delivered live babies at four centers in the United States during 1940 through 1960. Questionnaires were returned for 92.6% of the DES-exposed and 88.8% of the unexposed women.

Main Outcome Measures
Breast cancer incidence and mortality assessed from returned questionnaires and review of medical records and death certificates.

Main Results
The relative rate of breast cancer associated with DES exposure, after adjustment for demographic and reproductive variables, was 1.35 (95% confidence interval, 1.05 to 1.74). For 30 years or more following exposure, the relative rate was not appreciably higher (relative rate, 1.33; 95% confidence interval, 0.95 to 1.87) than that in earlier periods. Surveillance and increased detection seemed unlikely explanations for the increased risk, since DES-exposed women had excesses of both large and small breast cancers and the two cohorts reported similar breast cancer detection practices. A history of miscarriage before first term delivery was not associated with breast cancer occurrence.

Conclusion
Exposure to DES during pregnancy is associated with a modest but statistically significant increased risk of breast cancer. Contrary to prior indications, the risk does not appear to increase greatly over time. The findings are sufficient to exclude the possibility of a doubling of risk for the period of 30 or more years following exposure.

Sources

  • Breast cancer in mothers prescribed diethylstilbestrol in pregnancy. Further follow-up, Journal of the American Medical Association, NCBI PubMed, PMID: 8468763, 1993 Apr.
  • Featured image credit Benjamin Ranger.
DES DIETHYLSTILBESTROL RESOURCES

DES Mothers and Breast Cancer

A twenty-five-year follow-up study of women exposed to diethylstilbestrol during pregnancy

1978 Study Abstract

To assess the long-term effects of diethylstilbestrol we conducted a health survey among 693 mothers who had taken the drug during pregnancy and a comparable group of 668 who had not. These women had participated in a study during 1951-52 to evaluate the drug.

There were 32 (4.6 per cent) breast cancers among the 693 exposed and 21 (3.1 per cent) among the 668 unexposed, but the difference was not statistically significant (P = 0.16). No statistically significant differences occurred between the groups in any of the other categories of disease.

The occurrence of breast cancer in both groups was compared to the Connecticut State Tumor Registry for 1963-65. Compared to the registry data, a significantly (P less than 0.01) higher incidence of breast cancer occurred in both the exposed and unexposed groups at ages over 50. The reason for this increase is not known, but effects linked to the selection of mothers participating in the original clinical study cannot be excluded.

Sources

  • A twenty-five-year follow-up study of women exposed to diethylstilbestrol during pregnancy, The New England journal of medicine, NCBI PubMed, PMID: 628409, 1978 Apr.
  • Featured image credit Jeremy Wong.
DES DIETHYLSTILBESTROL RESOURCES

Follow-up study of male and female offspring of DES-exposed mothers

This follow-up study presents the effects of DES on the genital tract of male and female offspring of mothers who were part of a double-blind, placebo-controlled investigation during 1951 and 1952 aimed at determining the effect of DES on pregnancy

1977 Study Abstract

Epididymal cysts, hypotrophic testes, and capsular induration were the more common genital lesions found in 25% of 163 DES-exposed males as compared to 6% in 168 control males. Semen analysis data on 39 subjects of the DES-exposed group and 25 subjects of the control group showed that 26% of the DES-exposed group produced an ejaculate volume under 1.5 ml; no such cases were observed in the control group. The average values for sperm density ant total motile spermatozoa per ejaculate, although in the normal range, were more than two times lower in the DES-exposed group as compared to the controls. A quality score of greater than 10 (“severely pathologic semen”) was found in 28% of the DES-exposed group as compared to 0 in the control group. An association of pathologic semen quality with physical abnormalities was found only in the DES-exposed group. Two cases of azoospermia, one without genital abnormalities on physical examination and one with bilateral hypotrophic testes were observed so far in the DES-exposed group.

Eighteen percent of 229 DES-exposed female patients had irregular menstrual cycles (oligomenorrhea) as compared to 10% of 136 controls. The history of pregnancy revealed a lower incidence of pregnancy in the DES-exposed group (18%) than in the control group (33%). Circumferential ridges of the vagina and cervix were seen in 40% of 229 DES-exposed females but in none of 136 controls. Colposcopic findings in the vagina revealed adenosis in 66.8% of the DES-exposed females and in 3.6% of the control group. Dysplastic lesions were more prevalent in the vagina and cervix of the DES-exposed subjects.

No cases of cancer were observed in either the male or female offspring.

Sources

  • Follow-up study of male and female offspring of DES-exposed mothers, Obstetrics and gynecology, NCBI PubMed, PMID: 318736, 1977 Jan.
  • Features image credit Isaac Cabezas.
DES DIETHYLSTILBESTROL RESOURCES

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

Does the Administration of Diethylstilbestrol during Pregnancy have Therapeutic Value ?

Diethylstilbestrol usage was questioned by WJ Dieckmann in 1953

Conclusions

A strictly controlled clinical trial of the therapeutic value of diethylstilbestrol administered to patients during pregnancy in reducing the hazards of some of the late complications of pregnancy for mothers and babies has been reported.

The various complications were studied in the total unselected group of patients divided into primigravidas, primiparas, and multiparas. Then the groups were again studied after all groups were corrected to compare with the Smiths’.

The results of the administration of diethylstilbestrol in graduated amounts to 840 patients according to a schedule suggested by the Smiths were compared with the results of an identical placebo tablet given to 806 patients. Stilbestrol did not reduce the incidence of abortion, prematurity, or postmaturity. Premature babies of stilbestrol-treated mothers were no longer nor more mature for their gestational ages than comparable prematures in the control group of placebo-treated mothers. It did not decrease the incidence of perinatal mortality. It did not decrease the frequency of the toxemias of pregnancy.

Discussion Abstracts

“We too are disappointed, and apologetic., because we were instrumental in putting them to so much trouble in acquiring results that are still inconclusive.
“We also wish we had given a placebo to our controls.”
“We omitted from our analyses all patients who aborted prior to viability and did not accept those who had threatened to abort at any time early in pregnancy or include such cases in our control series.”

DR. GEORGE van S. SMITH, Brookline, Mass.

“We have never said that it should be given to all during pregnancies.”
“We do not recommend stilbestrol for pregnancy complications, …”

DR. OLIVE W. SMITH, Brookline, Mass.

“The one general conclusion to be drawn from this very painstaking study of Dieckmann and co-workers must be obvious to each of us; stilbestrol is no panacea.”
“We have a similar study in progress. At the present time 350 patients have completed their pregnancies. Treatment was begun prior to the sixteenth week. There seems no need to give the details of the results. The material was analyzed in much the same manner as that of Dieckmann and the results were virtually identical. In short, there was no difference in size of newborn infants, duration of pregnancy, occurrence of premature labor or of toxemia in the two groups. This short series gave the same results as the much longer series. It would seem to me, therefore, that these results indicate that stilbestrol for routine use has little value.

DR. WILLARD ALLEN, St. Louis, Mo

“We have followed Dr. Olive Smith’s work very carefully.

This experiment was designed in an attempt to learn whether diethylstilbestrol has therapeutic value. Our problem was to find out whether it is worth the time and effort and money to administer the drug to large segments of our population in an attempt to cut flown on the hazards of some of these pregnancy complications.

We have not proved that it is of value. All of om data are filed on IBM cards. These are available to any of you who wish to examine them. Concerning the length of time that the drug was taken by the patients, 15 weeks is the average time and 5 weeks i~ the minimum period.

We think that the number of patients studied and the methods useJ showed that stilbestrol has no therapeutic value in pregnancy. It is possible that that answer may not he correct, but it will take at least as many more patients just as carefully controlled to prove that stilbestrol administered prophylactically to normal or abnormal pregnant patients has any value in the prevention of the specific complications of pregnancy.”

DR. DAVIS (Closing)

Sources

From the Department of Obstetrics and Gynecology of the University of Chicago and the Chicago Lying-in Hospital Chicago, Ill.
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