DES (Diethylstilbestrol) Resource Guide 1980

National Women’s Health Network, 1980

DES-Guide 1980 cover image
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National Women’s Health Network,
Resource Guide 6, 1980

The sixth resource guide of the 1980 series published by the National Women’s Health Network concerns DES (diethylstilbestrol), a synthetic estrogen prescribed to women, usually during pregnancy, from the time of its discovery in 1938 and even after it was banned by the FDA in 1971.

As this guide details, direct exposure to DES increases the risk of breast cancer, while exposure in utero may lead to cancer or physical disabilities.

In addition to documenting the effects of DES, this guide also provides resources and information for mothers and daughters who have been exposed.

Sources
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DES exposure and the aging woman: mothers, sons and daughters

Increased risk of cancers for the DES-exposed

image of holding hands
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 for consumption.

2002 Study Abstract

Diethylstilbestrol (DES), the first orally active artificial estrogen ever developed, was prescribed to several million pregnant women during the 1940s through the 1960s in the mistaken belief that it reduced the risk of miscarriage.

In 1971, the US Food and Drug Administration contraindicated its use in pregnancy when DES was associated with the development of vaginal clear cell adenocarcinoma (CCA) in daughters exposed in utero.

In daughters whose mothers took DES during pregnancy, the drug has been associated with congenital malformations of the reproductive tract, fertility problems, a possible increased risk of cervical carcinoma in situ, and a presumed lifetime risk of vaginal and cervical CCA.

DES mothers have an increased risk of breast cancer (RR = 1.3).

DES sons have an increased prevalence of urogenital anomalies, and a possible increased risk of testicular cancer.

Sources and more information
  • DES exposure and the aging woman: mothers and daughters, Current women’s health reports, NCBI PMID: 12215312, 2002 Oct;2(5):390-3..
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Researching the cancer-causing effects that the artificial hormone DES has among young women

Lou Grant Inheritance, Season 3 Episode 17, 1980

While researching the cancer-causing effects that the artificial hormone DES has among young women, Billie discovers that she is a “DES daughter“.
Meanwhile, Rossi covers the legal struggle of a young woman who has been disowned by her family.

More info and videos
  • Lou Grant Inheritance, Season 3 Episode 17, Aired: 01/28/1980, Not Rated. Video published on 28 Dec 2012.
  • More DES Videos on our YT channel.
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A clinicopathologic study of vagina and cervix in DES-exposed progeny

Involution of vaginal adenosis – following DES exposure – occurs with increasing age

worried-girl image
The 1980 study findings suggest that involution of vaginal adenosis – following DES exposure – occurs with increasing age

1980 Study Abstract

In this survey of 210 women with a history and/or gross changes of the cervix and vagina characteristic of diethylstilbestrol (DES) exposure, changes related to vaginal adenosis were correlated with age. The mean age of women with columnar epithelium alone was 18.5 +/- 3.2 years, columnar epithelium with squamous metaplasia was 20.2 +/- 3.4 years, and squamous metaplasia alone was 23.0 +/- 2.7 years. These findings suggest that involution of vaginal adenosis occurs with increasing age. Involution of glands in the superficial stroma in most cases occurred concurrently with that of surface columnar epithelium. However, those deeply seated and complex glands in the stroma might lag in the metaplastic process and might persist. The pitfalls of misinterpretation of squamous cell changes in histologic samples were discussed. The lack of correlation between the colposcopic findings of mosaicism and/or punctuation and squamous cell neoplasia was confirmed in this study.

Sources and more information
  • A clinicopathologic study of vagina and cervix in DES-exposed progeny, Diagn Gynecol Obstet. 1980 Winter;2(4):245-56, NCBI PMID: 7215109.
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Colposcopic findings and intraepithelial neoplasia in diethylstilbestrol-exposed offspring

The Dutch experience, 1989

Colposcopy-Procedure image
Colposcopy in DES-exposed offspring in inexperienced hands can result in many unnecessary biopsies. Therefore colposcopic examination should be performed by expert colposcopists in referral diethylstilbestrol centers.
Colposcopy procedure image via colposcopyinfo.

1990 Study Abstract

Data from two regional diethylstilbestrol clinics for colposcopic evaluation of young women with a history of diethylstilbestrol exposure in utero are presented:

A total of 224 subjects with a well-documented history were enrolled in this study.

  • Structural anomalies of the cervix and vagina were found in 30%.
  • Vaginal epithelial changes were colposcopically observed in 65%,
  • including vaginal adenosis in 22%.
  • The prevalence rate of abnormal cytologic findings in the study group was 9%.
  • In half of these patients a low-grade intraepithelial neoplasia of the cervix and vagina was found.

It was concluded that colposcopy in diethylstilbestrol-exposed offspring in inexperienced hands can result in many unnecessary biopsies. Therefore colposcopic examination should be performed by expert colposcopists in referral diethylstilbestrol centers.

Sources and more information
  • Colposcopic findings and intraepithelial neoplasia in diethylstilbestrol-exposed offspring. The Dutch experience, NCBI PubMed PMID: 2589438, Am J Obstet Gynecol. 1989 Nov;161(5):1191-4.
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Payton v. Abbott Laboratories: an analysis of the Massachusetts DES class action suit

A landmark ruling for plaintiffs seeking class certification in DES suits

image of PubMed NCBI The Endocrine Society logo
The first case in which a judge has interpreted the requirements of Rule 23 of the Federal Rules of Civil Procedure to allow women exposed in utero to DES to sue as a class to determine liability for their injuries

In Payton v. Abbott Laboratories, U.S. District Court Judge Walter J. Skinner recently granted class certification to an action brought by twenty-seven Massachusetts women against major manufacturers of DES.
This is the first case in which a judge has interpreted the requirements of Rule 23 of the Federal Rules of Civil Procedure to allow women exposed in utero to DES to sue as a class to determine liability for their injuries.

  • This Note reviews the Payton certification in light of prior class action decisions involving DES and other types of claims, and of legal commentary on Rule 23.
  • This Note contends that Judge Skinner’s application of the Rule 23 requirements in Payton was procedurally correct, and recommends the class action device as an effective method for litigating such controversies.
  • Finally, this Note analyzes the implication of this landmark ruling for plaintiffs seeking class certification in DES suits and in suits presenting analogous factual situations.

Sources

  • Payton v. Abbott Laboratories: an analysis of the Massachusetts DES class action suit, NCBI, PMID: 7468600, 1980 Summer;6(2):243-82.
  • Full text on HeinOnline.
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Long-Term Effects on the Female Mouse Genital Tract associated with Prenatal Exposure to DES

Such prenatal studies with DES in mice may be helpful in understanding the role of estrogens in the functional development of the genital tract

Abstract

The association between treatment of pregnant women with Diethylstilbestrol (DES) and reproductive tract abnormalities in their female offspring is well known.
Reports of comparable in utero exposure in animals are few.

image of PubMed NCBI The Endocrine Society logo
Understanding the role of estrogens in the functional development of the genital tract.

In this paper, pregnant outbred mice were treated s.c. with daily doses of DES ranging from 0.01 to 100 µg/kg on Days 9 to 16 of gestation. This period corresponds with major organogenesis of the reproductive tract in the mouse. Additional groups of pregnant mice were treated during the same time interval with 100-µg/kg doses of either dimethylstilbestrol (DMS), a weakly estrogenic estructural analog of DES, or 17β-estradiol, a potent steroidal estrogen. When female offspring of mice gestationally exposed to DES were sacrificed at 12 to 18 months of age, lesions were found throughout their reproductive tracts. The vagina was characterized by excess keratinization and female hypospadias, and, at the dose of 100 µg/kg, 5 of 20 mice had epidermoid tumors of the vagina; in one of the 35 mice derived from mothers treated with DES (10 µg/kg), vaginal adenocarcinoma was observed. The cervix in the DES-exposed offspring was enlarged, even though the size of its lumen was not different from that in the controls. Stromal stimulation of the cervix was apparent, and a low incidence of benign (leiomyoma, papilloma) as well as malignant (stromal cell sarcoma, leiomyosarcoma) tumors were seen. There was evidence of stimulation in the epithelium, and stroma of the uterus and cystic endometrial hyperplasia was common; a low incidence of benign (leiomyomas) and malignant (adenocarcinoma, stromal cell sarcoma) tumors was observed. The ovaries of prenatally DES-treated females were cystic more often than were those of the corresponding controls; at the highest dose, three ovarian tumors were noted, and the fallopian tubes were inflamed and congenitally malformed. Genital tract tumors were not seen in 85 control females or in the 12 or 10 females exposed prenatally to estradiol or DMS, respectively. In fact, in 12- to 13-month-old females derived from mice exposed during pregnancy to DES (100 µg/kg), common findings, which were absent or in very low incidence in control, estradiol-treated, or DMS-treated mice, included: vaginal concretions and excess keratinization; cervical enlargement; uterine squamous metaplasia and cystic endometrial hyperplasia; and oviductal malformations. The differences in effects among DES, estradiol, and DMS may be linked to differences in relative bioavailability of the compounds to the fetal target tissue.

The results presented suggest a role for different embryonic rudiments as well as for tissue components in the observed long-term effects of gestational exposure to DES on the female reproductive tract. Moreover, such prenatal studies with DES in mice may be helpful in understanding the role of estrogens in the functional development of the genital tract and may ultimately provide a useful experimental model.

Sources:
  • Long-term effects on the female mouse genital tract associated with prenatal exposure to diethylstilbestrol, NCBI, PMID: 7193511, 1980 Nov;40(11):3988-99. Newbold RR.
  • Full text – American Association for Cancer Research, 40/11/3988 Cancer Res, 1980; 40:3988-3999.
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