Psychological effects of diethylstilbestrol exposure

Guilt: the most common problem among DES mothers

This 1977 study concluded that sensitivity and good communication on the part of medical personnel are recommended.

Study Abstract

The Journal of The American Medical Association, doi:10.1001/jama.1977.03270300056007, January 17, 1977

The psychological response of daughters and their mothers to discovery of in utero diethylstilbestrol (DES) exposure was studied.

At the DES Colposcopy Clinic, 41 daughters and 20 mothers were extensively interviewed. Twelve patients with abnormal cytology tests were controls.

Initial anxiety was usually followed by acceptance of the condition after examination and counseling. Patients responded best when informed of their problem by their mothers and when the relationship between mother and daughter was good. The majority of patients found colposcopy to be unpleasant; they tended to be disturbed in proportion to the degree of being upset about DES exposure. The most common problem among mothers was guilt.

A questionnaire survey of physicians showed that they had less concern for psychological problems than patients or mothers did. Sensitivity and good communication on the part of medical personnel are recommended.

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Management of females exposed to DES-type drugs ; 1977 recommendations

Vaginal and cervical cancers and other abnormalities associated with exposure in utero to diethylstilbestrol and related synthetic hormones

woman-at-hospital
1977 study and recommendations about vaginal and cervical cancers and other abnormalities associated with exposure in utero to diethylstilbestrol and related synthetic hormones. all you’ve been through.

1977 Study Abstract

All asymptomatic girls who wore exposed to diethylstilbestrol in utero should receive a thorough pelvic examination at menarche or if they have reached 14 years of age. Younger girls should be examined if they develop abnormal bleeding or discharge. Whenever prenatal exposure is probable and theme are symptoms of discharge, further investigation is imperative, regardless of the patient’s age. This investigation should not be concluded until it is certain that no lesion is present.

Before the examination is undertaken, the entire procedure should be thoroughly discussed with the patient (and her mother on father if she is a minor).

The examination should include inspection and palpation, Papanicolaou smear (cervix and vagina), and an iodine staining test of the entire cervix and vagina. Abnormal areas, including those that do not stain with iodine, should be biopsied.  This procedure can be performed in the physician’s office with small biopsy instruments and without significant discomfort.

For the very young patient who has symptoms that require investigation, anesthesia may occasionally be required be fore an examination. A small speculum permits adequate visualization of the vagina without undue discomfort in younger patients.

With asymptomatic females, if adequate examination is not possible at the initial visit, vaginal tampons should be used for a few months to allow an adequate examination later without discomfort. Colposcopy is a useful adjunct to this examination, but it is not essential. Utilizing its low power magnification to examine the vagina and cervix, the physician can identify areas of glandular tissue (adenosis) in the vagina on on the cervix. This identification permits directed rather than “blind” biopsies. When used in con junction with the iodine staining test and selected biopsy, colposcopy permits precise recording of observed abnormalities and their appraisal at fixed intervals.

The patient exposed to DES-type drugs should be followed on a regular basis. After a normal initial examination, annual pelvic examinations with cervical and vaginal cytology and iodine staining are probably adequate. If any abnormalities are noted during the initial evaluation, more frequent follow-up examinations are suggested (every 3 to 6 months, depending on the severity of the findings).

Locally destructive measures such as cauterization, cryosurgery, or excision can be utilized if atypical changes such as marked squamous dysplasia on carcinoma in situ of the vagina or cervix are found on biopsy.

Sources and more information
  • Vaginal and cervical cancers and other abnormalities associated with exposure in utero to diethylstilbestrol and related synthetic hormones, Cancer Research, 1977 Apr.
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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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The management of DES-exposed women: one physician’s approach

It is clear that DES has long-term effects that may develop over time

The finding of an incidence of 47% of cervical or vaginal intraepithelial neoplasia in 34 patients aged 10 to 26 years so treated to date indicates a high risk of potential candidacy for squamous carcinoma of the vagina or cervix in later years. Away we try to escape by Kei Kojishi.

1976 Study Abstract

The female offspring of diethylstilbestrol DES-treated mothers are examined cytologically and colposcopically annually, starting at the age of seven years no treatment is indicated until a colposcopic atypical transformation zone occurs. With its occurrence all the abnormal epithelium (squamous or columnar) is excised from the vagina and cervix under colposcopic guidance in the hospital or in the office under local anesthesia. The procedures are done in stages to minimize scarring and to eliminate the possibility of vaginal-cervical adhesions or vaginal shortening. The finding of an incidence of 47% of cervical or vaginal intraepithelial neoplasia in 34 patients aged 10 to 26 years so treated to date indicates a high risk of potential candidacy for squamous carcinoma of the vagina or cervix in later years.

Sources and more information
  • The management of DES-exposed women: one physician’s approach, The Journal of reproductive medicine, NCBI pubmed 957347; 16(6):285-8. 1976 Jun.
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Refocusing on the gynecological and obstetrical consequences of intrauterine exposure to DES

Full examination of the DES-exposed pregnant patients is advised, including colposcopy and hysterosalpingography

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

1991 Study Abstract

The oncological and obstetrical follow-up is described of 321 patients who presented between 1981 and 1988 in the St Radboud Hospital with a history of intrauterine diethylstilbestrol(DES) exposure.

In 45 out of 321 cases cytological abnormalities were found including 20 cases of cervical intraepithelial neoplasia (CIN). No relation could be established between CIN and the extension of the cervical adenosis.

  • 22% of 87 evaluable pregnancies terminated in spontaneous abortion,
  • 13% of the patients delivered immaturely
  • and 27% prematurely.

These percentages were significantly higher than in the rest of the hospital population. The consequences of intrauterine exposure to DES are discussed.

Full examination of the patients is advised, including colposcopy and hysterosalpingography. If abnormalities are present it is advised to offer a timely cerclage in case of pregnancy.

Sources and more information
  • Refocusing on the gynecological and obstetrical consequences of intrauterine exposure to diethylstilbestrol (DES)., Nederlands tijdschrift voor geneeskunde, 1991 Jan 19;135(3):89-93., NCBI PMID: 1996166.
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Development of DES-associated clear-cell carcinoma: the importance of regular screening

Regular and frequent PAP smears are needed for DES-affected women

pap-smear image
This 1979 study underscores the necessity for frequent vaginal cytologic smears and pelvic examinations at intervals no greater than 6 months for the DES-affected women.

1979 Study Abstract

Because the rate of malignancies in young women exposed in utero to diethylstilbestrol (DES) is low, appropriate population screening methods have not been established. A case is presented that is believed to represent the first reported instance of a DES-exposed daughter who developed clear cell adenocarcinoma of the vagina after initially negative examinations. The patient was followed with Papanicolaou smears, pelvic examinations, and colposcopy every 6 months for 2 years prior to the discovery of malignancy. Initially negative, Papanicolaou smears successfully predicted the presence of an early adenocarcinoma. Palpation aided by colposcopy allowed directed biopsy of the small asymptomatic lesion.

This case underscores the necessity for frequent vaginal cytologic smears and pelvic examinations at intervals no greater than 6 months. Colposcopy is indicated to direct biopsies when an abnormal cytologic smears is reported or when abnormal bleeding or discharge occurs. Biopsy of any palpable lesion is mandatory.

Sources and more information
  • Development of DES-associated clear-cell carcinoma: the importance of regular screening, Obstetrics and Gynecology 1979 Mar;53(3):293-9, NCBI PMID: 424100.
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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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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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Cervical squamous carcinoma in situ and vaginal adenosis cancer risk in DES-exposed offspring

Cancer risk in diethylstilbestrol-exposed offspring, 1976 findings

woman-and-cancer
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.

1976 Study Abstract

The occurrence of columnar epithelium in the vagina (vaginal adenosis) in young women with intrauterine exposure to diethylstilbestrol (DES) during the first trimester of pregnancy was observed in 231 patients (82 per cent of 280 cases who underwent colposcopic study). Extension of columnar epithelium onto the portio of the cervix was present in the remaining 18 per cent of the cases. Abnormal colposcopic findings were present in the transformation zone in 96 per cent of the patients with vaginal adenosis. Directed biopsy revealed four cases of vaginal and/or cervical squamous carcinoma in situ (CIS), two cases of severe dysplasia, five cases of moderate, and 29 cases of mild dysplasia. The prevalence of CIS in DES-exposed girls (1.4 per cent) was nearly five times the prevalence rate of CIS in a control group of 5,808 DES-unexposed women (0.44 per cent). This finding correlates well with the hypothesis that the genesis of squamous intraepithelial neoplasia is specifically related to the extent and surface area of the vaginal transformation zone. An unusual case of invasive squamous carcinoma in a DES-exposed young girl is presented, which represents the initial observation of this association to date.

Sources and more information
  • Cancer risk in diethylstilbestrol-exposed offspring, Mattingly RF, Stafl A., NCBI PMID: 984124, Am J Obstet Gynecol. 1976 Nov 1;126(5):543-8.
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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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