Colposcopic evaluation of DES-exposed progeny at two large medical centers: the squamous neoplasia problem

The squamous neoplasia problem, Southern medical journal, 1978

Colposcopy-Unit
Cases of vaginal adenosis in young women should be investigated and screened appropriately, and preferably referred to centres where colposcopic expertise is available.

1978 Study Abstract

Two hundred eight patients with confirmed or suspected diethylstilbestrol exposure were examined colposcopically at two separate medical centers.

  • Cervicovaginal ridges were present in 90 (43.3%)
  • and ectopy was found in 188 (90.4%) of the patients.
  • Evidence of vaginal adenosis was present in 122 (58.6%) of the cases.

Seventy-four percent of the patients had abnormal colposcopic findings:

  • 15.4% having columnar epithelium on the surface of the vagina
  • and 66% having abnormal transformation zones (white epithelium, punctation, mosaic).
  • Twenty patients (9.6%) were initially identified histologically as having squamous dysplasia. Subsequent review of the histologic material in these cases could document only two cases of significant squamous dysplasia, both severe, the remainder having immature, atypical metaplasia or possibly very mild dysplasia.

This finding emphasizes the problems encountered in histologically differentiating squamous neoplasia from the peculiar metaplasia found in these patients, thereby making it difficult to establish whether these patients are at increased risk for the development of squamous neoplasia..

Sources and more information
  • Colposcopic evaluation of DES-exposed progeny at two large medical centers: the squamous neoplasia problem, Southern medical journal, NCBI PMID: 663728, 1978 Jul.
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Design and preliminary observations of the National Cooperative Diethylstilbestrol Adenosis Project

Obstetrics and Gynecology, DESAD Project, 1978

DESAD-Project logo
Aims of the 1978 DESAD Project: to fill urgent needs for information on the prevalence and incidence of structural and epithelial abnormalities or neoplastic changes and their complications in DES Daughters.

1978 Paper Abstract

The National Cooperative Diethylstilbestrol Adenosis (DESAD) Project has completed the major portion of its enrollment phase with the examination of more than 3000 daughters of women taking synthetic nonsteroidal estrogens (denoted diethylstilbestrol DES) during pregnancies occurring from the early 1940s to the mid-1960s.

The aims of the Project are to fill urgent needs for information on the prevalence and incidence of structural and epithelial abnormalities or neoplastic changes and their complications in these young women.

Participants are grouped by mode of entry as identified by prenatal record review (40.1%), documented as DES-exposed but walking in (25.1%), or referred (22.8%) to the DESAD Project for examination, and not documented as exposed but having gynecologic abnormalities typical of those associated with DES exposure (12.0%).

This study cohort, in part having paired controls, will be examined annually for at least 5 years. Details of the design and selected preliminary findings are reported.

Sources and more information
  • Design and preliminary observations of National Cooperative Diethylstilbestrol Adenosis (DESAD) Project, Obstetrics and Gynecology 1978 Apr;51(4):453-8, NCBI PMID: 662228.
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Squamous cell carcinoma in situ of the vagina and cervix after intrauterine DES exposure

All cases of adenosis should be followed by colposcopy

young-woman
This 1978 study recommended that all cases of adenosis be followed by colposcopy.
I think I will just image by Mary.

1978 Study Abstract

Two patients exposed in utero to maternal diethylstilbestrol DES ingestion presented with adenosis. Each developed intraepithelial neoplasia in an area of active metaplastic change.

The question is raised whether a continuum exists beginning with DES exposure and proceeding through the occurrence of adenosis and active squamous metaplasia to dysplastic alteration and finally squamous neoplasia.

Since the cytologic smear is negative in 50% of cases during the dysplastic phase, it is recommened that all cases of adenosis be followed by colposcopy.

Sources and more information
  • Squamous cell carcinoma in situ of the vagina and cervix after intrauterine DES exposure, NCBI PMID: 683639, Obstet Gynecol. 1978 Jul;52(1 Suppl):30S-33S.
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Higher risk of developing squamous neoplasia following prenatal Diethylstilbestrol exposure

Incidence of squamous neoplasia of the cervix and vagina in DES-exposed

High-Grade-Squamous-Intraep
In this 1978 study, it appeared that women with in utero DES exposure may be at a higher risk of developing squamous neoplasia compared with non-DES-exposed women.

1978 Study Abstract (1)

Two hundred and fifty patients were examined because of a history of in utero exposure to diethylstilbestrol (DES) or because of the presence of physical findings suggesting such exposure. One thousand biopsies were examined for the presence of neoplasia and then compared to the colposcopic findings. There were no cases of glandular or squamous cell carcinoma. Fifteen (6 per cent) of the patients had squamous cell dysplasia. The degree of dysplasia was mild in 11 and moderate in only 4 (1.6 per cent) of the women. The majority of the cases of dysplasia involved the cervix, whereas the vagina was involved in only four cases, with simultaneous cervical dysplasia in three of these. Patients with cervical mosaic and white epithelium had dysplasia on biopsy much more frequently as compared with patients with similar colposcopic appearances in the vagina. Our results suggest a low incidence of significant squamous precancerous change in the DES-exposed population and provide evidence that colposcopic data concerning dysplasia pertinent to the cervix cannot be applied without modification to the evaluation of dysplasia in vaginal adenosis.

1978 Study Abstract (2)

Among 199 women from 12 to 30 years of age who had been exposed to DES in utero, the colposcopic evaluation of the vagina and cervix was considered normal for only 13.6%. The incidence of colposcopically detected lesions was not related to the trimester of DES exposure, the patient’s age, use of oral contraceptives, or presenting symptoms. Areas of punctation, mosaic patterns, white epithelium, and keratosis were not considered areas of adenosis. Cervical bands, hoods, cock’s combs, etc., were considered as part of the cervix. Under this definition adenosis of the vagina was diagnosed in only 14.1% of the patients. Eight (4.0%) women were found to have cervical intraepithelial neoplasia (CIN), Grade 3 lesions, and an additional 36 (14.1%) women were found to have CIN, Grade 1 lesions based on the light microscopy evaluation of directed biopsies. There were no cases of clear cell adenocarcinoma. It appears that women with in utero DES exposure may be at a higher risk of developing squamous neoplasia compared with non-DES-exposed women.

Sources and more information
  • In utero exposure to DES. Evaluation and followup of 199 women,
    NCBI PMID: 662229, Obstet Gynecol. 1978 Apr;51(4):459-63.
  • Vaginal and cervical squamous cell dysplasia in women exposed to diethylstilbestrol in utero,
    NCBI PMID: 717453, Am J Obstet Gynecol. 1978 Nov 1;132(5):537-44.
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Squamous cell dysplasia and carcinoma in situ of the cervix and vagina after prenatal DES exposure

Squamous cell abnormalities of the vagina and cervix were evaluated in 1424 women exposed to diethylstilbestrol (DES) in utero

dysplasia
These 1978 data suggest that both cytology and biopsy of abnormal segments of the vagina and cervix remain an integral part of the examination of the DES-exposed female during long-term follow-up . Image by Helga Weber.

1978 Study Abstract

Squamous cell abnormalities of the vagina and cervix were evaluated in 1424 women exposed to diethylstilbestrol (DES) in utero. The prevalence of dysplasia was 2.1% and the incidence 0.85/100 person-years of followup. The dysplastic epithelial changes were almost always mild in women with no prior history of dysplasia and was slightly more frequent in the cervix than the vagina. Severe dysplasia and carcinoma in situ (CIS) were encountered only in those subjects specifically referred because of those abnormalities. The most common problem in the diagnosis of these squamous cell changes was the misinterpretation of mature and immature metaplastic cells for dysplastic squamous cells. Discordance between biopsy and cytology was common-place in the detection and followup of dysplasia, especially when it was mild. There were no instances in the study where cytology and biopsy samples from the vagina were both abnormal concurrently. Colposcopically directed biopsies did not increase the frequency of confirmation of cytologic findings. These data suggest that both cytology and biopsy of abnormal segments of the vagina and cervix remain an integral part of the examination of the DES-exposed female during long-term follow-up studies.

Sources and more information
  • Squamous cell dysplasia and carcinoma in situ of the cervix and vagina after prenatal exposure to diethylstilbestrol,
    NCBI PMID: 652199, Obstet Gynecol. 1978 May;51(5):528-35.
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A Twenty-Five-Year Follow-Up Study of Women exposed to DiEthylStilbestrol during Pregnancy

DES 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 for consumption.

To assess the long-term effects of diethylstilboestrol (DES) 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,
    NCBI, PMID: 628409, N Engl J Med. 1978 Apr 6;298(14):763-7.
  • Full text: NEJM, 197804062981403,
    N Engl J Med 1978; 298:763-767April 6, 1978DOI: 10.1056/NEJM197804062981403
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Women and the Crisis in Sex Hormones

Complete handbook by Barbara Seaman, published in 1981, about birth control, DES, menopause, remedies and more…

Women and the Crisis in Sex Hormones book cover image
Complete handbook published in 1981 about birth control, DES, menopause, remedies and more…

Barbara Seaman, author of The Greatest Experiment Ever Performed on Women, previously wrote a book entitled The Doctor’s Case Against the Pill, which was almost single-handedly responsible for calling the attention of Senator Nelson and his committee on drugs, as well as that of the public, to the dangers of hormone contraceptives for women, as well as to the indifference and perhaps denial of the medical profession generally. Now, in the Women and the Crisis in Sex Hormones book coauthored by her husband, a psychiatrist and psychopharmacologist, the subject is extended to a comprehensive examination of the entire contraceptive field.

Written with a biting and sardonic humor at times, it is a remarkable piece of investigative reporting, comprehensive enough to serve as a reliable reference work. It considers alternatives to hormonal contraception, including the diaphragm, cervical cap, intrauterine device, foam, current rhythm methods, sterilization, abortion, the condom, vasectomy, and a pill for men. It considers menopause and the use of hormones in relation to it.

Sources JAMA 1978;239(20):2179. doi:10.1001/jama.1978.03280470091039

The first chapters of this book are about DES history.

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