Vaginal adenosis and diethylstilboestrol

The size of the problem in the UK is small, but clinicians should be aware that it exists

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.

1984 Study Abstract

Unlike the effects of Thalidomide on the developing child, those of DES are not readily apparent at birth. The administration of diethylstilbestrol DES and its sequelae are in this respect a unique medical experience. Fortunately, with the realization that late sequelae occur, the use of the drug in pregnancy has been discontinued and the problems are likely to be self-limiting.

The link between DES and particularly the benign changes in the vagina and cervix (adenosis) seems well established. The association between this drug and the development of genital malignancies is less clear, and the very low incidence in the prospective studies in the USA supports this concept.

The size of the problem in the UK is small, but clinicians should be aware that it exists. Cases of vaginal adenosis in young women should be investigated and screened appropriately, and preferably referred to centres where colposcopic expertise is available. Treatment of simple vaginal adenosis should be avoided.

Sources and more information
  • Vaginal adenosis and diethylstilboestrol, British journal of hospital medicine 1984 Jan;31(1):42-8, NCBI PMID: 6697040.
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Atypical vaginal adenosis and cervical ectropion, Association with CCAC in DES-exposed offspring

Atypical vaginal adenosis and atypical cervical ectropion of the tuboendometrial type are precursors of clear cell adenocarcinoma

Cervical-Ectropion-Analysis image
The frequency with which atypical tuboendometrial glands in the vagina and cervix were associated with the carcinomas and the proximity of the former to the latter provide strong evidence that atypical vaginal adenosis and atypical cervical ectropion of the tuboendometrial type are precursors of clear cell adenocarcinoma.

1984 Study Abstract

Knowledge of the evolution of clear cell adenocarcinomas of the vagina and cervix in diethylstilbestrol-exposed progeny has remained elusive despite the known topographical association of these tumors with the tuboendometrial form of vaginal adenosis and cervical ectropion.

Twenty radical hysterectomy or radical hysterectomy and vaginectomy specimens of clear cell adenocarcinoma of the vagina or cervix were serially blocked in toto;

  • tuboendometrial epithelium was found in the vagina in 19 (95%) of the cases, usually in greatest concentration at the margin of the tumor, particularly inferiorly.
  • Foci of atypical tuboendometrial epithelium were identified in 16 (80%) of the cases, almost always immediately adjacent to the tumor.

Twenty-five of a second group of 47 specimens in which only substantial portions of the vagina or cervix adjacent to a clear cell adenocarcinoma were available for examination also had foci of atypical tuboendometrial epithelium.

The frequency with which atypical tuboendometrial glands in the vagina and cervix were associated with the carcinomas and the proximity of the former to the latter provide strong evidence that atypical vaginal adenosis and atypical cervical ectropion of the tuboendometrial type are precursors of clear cell adenocarcinoma.

Sources and more information
  • Atypical vaginal adenosis and cervical ectropion. Association with clear cell adenocarcinoma in diethylstilbestrol-exposed offspring, Cancer. 1984, Sep 1, ;54(5):869-75. Robboy SJ, Young RH, Welch WR, Truslow GY, Prat J, Herbst AL, Scully RE, NCBI PMID: 6537153.
  • Full paper: Cancer Volume 54, Issue 5, Article first published online: 29 JUN 2006, PDF.
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Structural anomalies of the cervix and vagina in women enrolled in the Diethylstilbestrol Adenosis Project

Prevalence rate of the anomalies lower among subjects who had been pregnant, and higher among those with later age at menarche

woman-thinking
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. Contemplation by Rennett Stowe.

1984 Study Abstract

Among women exposed in utero to diethylstilbestrol (DES) and enrolled in the Diethylstilbestrol Adenosis (DESAD) Project, structural anomalies of the cervix or vagina were found in 25% of the 1,655 subjects identified by review of prenatal records, 43% of the 800 who themselves requested entry into the project, and 49% of the 1,089 referred by physicians but in only 2% of the 963 control subjects. Among the 367 cases found by record review to have complete information on the DES exposure, multivariate analysis indicated close association of the anomalies with the gestational week of first exposure and the total dose. Also, the prevalence rate of the anomalies was lower among subjects who had been pregnant and higher among those with later age at menarche.

Sources and more information
  • Structural anomalies of the cervix and vagina in women enrolled in the Diethylstilbestrol Adenosis (DESAD) Project, Am J Obstet Gynecol, NCBI PMID: 6691382, 1984 Jan 1;148(1):59-66.
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Increased Incidence of Cervical and Vaginal Dysplasia in Diethylstilbestrol-Exposed Young Women

A DES Experience of the National Collaborative Diethylstilbestrol Adenosis Project.

Cervical-Dysplasia-Testing image
In this 1984 study, the incidence rate for dysplasia and carcinoma in situ was significantly higher in the women exposed to diethylstilbestrol.

1984 Study Abstract

The incidence rates of dysplasia and carcinoma in situ (CIS) of the cervix and vagina were determined in 3,980 young women exposed prenatally to diethylstilbestrol. Strict criteria were developed to minimize selection bias among the subset of 744 pairs of matched exposed and unexposed (control) cohort participants, all of whom were identified through review of prenatal obstetrical records. A high degree of compliance was achieved throughout the seven-year study period since in each group about 90% of the women remained as active participants, kept 77% of the annual anniversary examinations, and had separate Papanicolaou smears of the cervix and vagina performed in 99% of the anniversary examinations. The incidence rate for dysplasia and CIS was significantly higher in the women exposed to diethylstilbestrol than in those not exposed in the matched cohort (15.7 v 7.9 cases per 1,000 person-years of follow-up). The rates were higher in the exposed women if squamous metaplasia extended to the outer half of the cervix or onto the vagina. In other respects, the matched cohorts were strikingly similar.

Sources and more information
  • Increased incidence of cervical and vaginal dysplasia in 3,980 diethylstilbestrol-exposed young women. Experience of the National Collaborative Diethylstilbestrol Adenosis Project, NCBI PMID: 6502858, JAMA. 1984 Dec 7;252(21):2979-83.
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