Cervical intraepithelial neoplasia associated with exposure to diethylstilbestrol in utero

Obstetical Gynecology, Clinical and Pathologic Study 1981

intraepithelial-neoplasia image
Orr JW Jr, Shingleton HM, Gore H, Austin JM Jr, Hatch KD, Soong SJ., Obstetrics and Gynecology 1981.

1981 Study Abstract

The anatomic, colposcopic, cytologic, and histologic findings of the cervix in 300 women exposed to diethylstilbestrol (DES) in utero are reported.

Structural cervical abnormalities were found in 51.7% of these patients and an abnormal colposcopic examination was present in 50.6%. The initial interpretation of the pathologic specimens revealed that 26.6% of patients had cytologic or histologic evidence of cervical dysplasia. A uniform pathologic review demonstrated that 10.8% of the cytologic specimens and 37.5% of the histologic specimens had been overread by the initial pathologist. A correlation of the review cytology and histology revealed that the Papanicolaou smear sensitivity for the prediction of abnormal histology was 83.9% and specificity was 86.3%. The probability of an atypical cytologic finding predicting an abnormal histologic pattern was highly significant (P less than .00001). Colposcopic and structural cervical abnormalities were not predictive of an abnormal histologic diagnosis. Of the 18 patients (6%) with histologic evidence of mild-moderate dysplasia, 12 have been followed with no treatment, and cytologic and colposcopic examination has been normal. Marked dysplasia-carcinoma in situ was found in 14 patients (4.7%). Their therapy is summarized.

These data strongly suggest that women exposed to DES may be followed safely with Papanicolaou smears and colposcopic examinations provided that both cytopathologists and colposcopists are cognizant of the metaplastic changes in the DES progeny that distinguish them from patients with cervical intraepithelial neoplasia (CIN) who were not exposed to DES. Biopsy should be performed only if indicated by cytologic atypia, colposcopic evidence of advanced CIN, or the presence of an invasive lesion.

Sources and more information
  • Cervical intraepithelial neoplasia associated with exposure to diethylstilbestrol in utero: a clinical and pathologic study, Obstet Gynecol. 1981 Jul;58(1):75-82, NCBI PMID: 7195532.
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Developmental effects of Diethylstilbestrol in pregnancy

Medical – Gynecology & Obstetrics and Urology, 1981

Developmental effects of diethylstilbestrol (DES) in pregnancy book cover image
Taken from DES books album on Flickr.

Unknown Binding: 203 pages

Publisher: Thieme-Stratton (1981)

Language: English

Written by Herbst, Arthur L,
and Bern, Howard A.

Check-out DES books album on Flickr.

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Market Share Liability for DES (Diethylstilbestrol) Injury

A New High Water Mark in Tort Law: Sindell v. Abbott Laboratories

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University of Nebraska College of Law review, 1981

Abstract

In Sindell v. Abbott Laboratories, the California Supreme Court discussed intra-industry liability for adverse effects of drugs and adopted the market share liability theory for DES injuries. Although the majority purported to shift only the burden of proving causation from the plaintiff to the defendants, the effect of its adopting the intra-industry joint liability concept (or, more specifically, the market share doctrine) is to guarantee that the plaintiff will prevail on the causation issue. By departing from traditional tort doctrine and effectively eliminating causation as an issue, “‘[m]arket share’ liability thus represents a new high water mark in tort law.” This Note analyzes Sindell and the various approaches taken to overcome the obstacle of product identification in DES cases. In addition, it examines the legal, social, and economic ramifications of intra-industry joint liability.

Sources
  • Market Share Liability for DES (Diethylstilbestrol) Injury: A New High Water Mark in Tort Law: Sindell v. Abbott Laboratories, 26 Cal. 3d 588, 607 P.2d 924, 163 Cal. Rptr. 132, cert. denied, 101 S. Ct. 285 (1980), Barbara J. Koperski, University of Nebraska College of Law.
  • Full text, Nebraska Law Review, Volume 60 | Issue 2 Article 9, 1981
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Statutes of limitations: the special problem of DES suits

Two methods that DES plaintiffs may be able to use to overcome the potential statutes of limitations bar are discussed

image of PubMed NCBI The Endocrine Society logo
This Note discusses two methods that DES plaintiffs may be able to use to overcome the potential statutes of limitations bar: (1) the discovery rule, and (2) state provisions which toll the statute of limitations for minors.

In 1971, medical studies determined that DES causes a rare type of vaginal cancer in a small number of daughters of mothers who took DES during pregnancy. Subsequently, medical studies determined that exposure to DES can cause other vaginal abnormalities in the daughters, some of which may be precancerous.

As a result of these discoveries, many lawsuits have been filed by these daughters against DES manufacturers. Many DES suits may be barred by statutes of limitations, both because the number of years between the daughters’ exposure to DES in utero and the discovery that DES can cause injuries exceeds the statutory period, and because the cancer or other injuries caused by DES may not develop for many additional years.

This Note discusses two methods that DES plaintiffs may be able to use to overcome the potential statutes of limitations bar:

  1. the discovery rule,
  2. and state provisions which toll the statute of limitations for minors.
  • The Note contends that courts should apply an expanded discovery rule to DES suits to avoid the unfair result of barring a claim before the plaintiff could have known that she had a cause of action.
  • In addition, the Note argues that the injury which causes the statute of limitations to begin to run in DES suits should not be rigidly defined.
  • Finally, the Note urges that courts allow eligible DES plaintiffs to take advantage of applicable state provisions that toll the statute of limitations for minors.

Sources

  • Statutes of limitations: the special problem of DES suits, NCBI, PMID: 7258194, 1981 Spring;7(1):91-106.
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Dysplasia and Cytologic Findings in 4589 Young Women enrolled in DiEthylStilbestrol-Adenosis Project

DiEthylStilbestrol usage review buttress the need for adequate and rigorous research into the use of drugs in pregnancy and ensure that they do more good than harm before being introduced

Abstract

image of PubMed NCBI The Endocrine Society logo
DiEthylStilbestrol usage review buttress the need for adequate and rigorous research into the use of drugs in pregnancy and ensure that they do more good than harm before being introduced.

This report presents the cytologic findings and the rates of dysplasia for 4,589 young women enrolled in the National Cooperative Diethylstilbestrol-Adenosis (DESAD) Project. Mucinous columnar cells and/or metaplastic squamous cells with or without mucinous droplets were encountered in 22% of vaginal scrape smears from all diethylstilbestrol (DES)-exposed participants identified by review of prenatal records and in 43% of women in whom vaginal epithelial changes (VEC) were observed by colposcopy or by iodine staining. The frequency of cellular findings in the vaginal scrape smears was closely related to the timing of the administration of the DES to the mother. With increasing age of the daughters, the overall frequencies of both the mucinous and metaplastic cells decreased; relative to each other, an increasing proportion was metaplastic squamous cells. These data suggest that, as the women grow older, vaginal adenosis regresses by the process of squamous metaplasia. Endometrial type cells were found in 2% of vaginal scrape smears. Their cyclical occurrence during the menstrual cycle and lack of correlation with the presence of VEC indicated an origin from the uterine corpus rather than the tuboendometrial type of adenosis. Squamous cell dysplasia of the vagina and cervix was detected by biopsy or scrape smear specimens in 1.8% of DES-exposed women in the record review group. The rate of unexposed women was twice as high. In general, the rates of dysplasia were higher in the cervix than vagina, and the more severe degrees of dysplasia were encountered only in those women who were referred to the DESAD Project or who themselves requested entry. Four patients who were referred or who themselves requested entry were found to have clear cell adenocarcinoma of the vagina. The vaginal smear provided the first clue to the presence of an abnormality in three of them.

Sources

  • Dysplasia and cytologic findings in 4,589 young women enrolled in diethylstilbestrol-adenosis (DESAD) project, NCBI, PMID: 7195652, Am J Obstet Gynecol. 1981 Jul 1;140(5):579-86.
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DES: The Complete Story

Possibly the most comprehensive book on Diethylstilbestrol

a Book by Cynthia Laitman Orenberg

DES the complete story book cover image
A comprehensive handbook on DES, diethylstilbestrol, explains the potential effects of the drug on mothers and their children and provides practical information for those exposed to the drug.

This prize-winning book provides comprehensive information on every aspect (including legal info) of the drug, DES, the artifical estrogen that was given to millions of pregnant women in the mistaken belief that it would prevent miscarriage. It is clearly written with the consumer in mind, well-organized and still accurate, even more than two decades since its publication.

Sources: Amazon customer review

Abstract:

Mrs Orenberg, a medical editor and writer for the University of Wisconsin Medical School, has written a treatise on the effects of diethylstilbestrol (DES) from the perspective of a mother whose daughter was exposed in utero to this drug. In 200 pages, she relates in lay terms essentially what is considered to be current knowledge regarding the development of DES, the first inexpensive, orally effective estrogenic substance; the clinical trials carried out by the Smiths in the 1940s regarding its usefulness in certain complications of pregnancy; its subsequent widespread use in several million pregnant women; the controlled double-blind studies that eventually demonstrated it to be no more effective than a placebo; the study in Boston by Herbst, Ulfelder, Scully, and Poskanzer that related exposure in utero to this drug to the development of a rare clear-cell adenocarcinoma of the vagina in several young women; and the subsequent establishment of a …

  • Sources: JAMA. 371088 1982;247(14):2027. doi:10.1001/jama.1982.03320390085060.
  • Check-out this DES books album on Flickr.
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DiEthylStilbestrol and other Sex Hormones during Pregnancy

DES has terrible side-effects in DES Daughters, DES Sons, DES Grand-Children…

Diethylstilbestrol and other sex hormones during pregnancy
In utero exposure to Diethylstilbestrol is associated with terrible side-effects in DES Daughters, DES Sons, DES Grand-Children

Intrauterine exposure to diethylstilbestrol (DES) has been associated with this subsequent rare development of clear cell adenocarcinoma of the vagina and cervix in exposed female progeny. These tumors have been seen thus far in patients between the ages of 7 and 29 years. In addition, nonmalignant epithelial and structural genital alterations have been frequently observed. The epithelial changes of adenosis, ectropion, metaplasia, and potential neoplasia are considered. Thus far, no increased risk of squamous cell neoplasia has been demonstrated in DES-exposed subjects. However, increased pregnancy wastage, including premature birth, does appear to be more common among DES-exposed women; this increase may be related to the structural uterine and cervical changes that have occurred. DES-exposed men have been demonstrated to have anatomic genital changes, but the effects of these changes, if any, on male infertility are not known. Masculinization of the female external genitalia, including phallic enlargement and labioscrotal fusion, has been reported following intrauterine exposure to certain progestational agents and androgens.

Sources: Diethylstilbestrol and other sex hormones during pregnancyNCBI, Dr Herbst A, Nov 1981.

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