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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Identification and management of DES-exposed women

Emphasis has been placed on screening for clear cell adenocarcinoma rather than squamous cell carcinoma and reproductive alterations

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Greater effort must be made by practitioners to identify and screen for DES exposure in their practices, as well as to educate the public regarding the health risks posed by DES exposure so that affected women may be reached and receive care.

1988 Study Abstract

Diethylstilbestrol (DES), a synthetic estrogen compound, was prescribed to many women with history of miscarriage between the years 1940 and 1971.

As a result of prolonged use of DES in gynecological practice, an estimated 1 million to 1.5 million women were exposed prenatally, resulting in multiple upper and lower genital tract abnormalities. These anomalies may affect reproductive function and place women at greater risk for developing clear cell adenocarcinoma (peak incidence at age 19) and squamous cell carcinoma of the vagina and cervix (peak incidence at ages 35 to 40).

Emphasis has been placed on screening for clear cell adenocarcinoma rather than squamous cell carcinoma and reproductive alterations. Despite the previous emphasis during the 1970s and a subsequent decline in public and practitioner awareness, women are at risk for the known effects of DES exposure until the year 2010. Greater effort must be made by practitioners to identify and screen for DES exposure in their practices, as well as to educate the public regarding the health risks posed by DES exposure so that affected women may be reached and receive care.

Sources and more information
  • Identification and management of DES-exposed women, The Nurse practitioner, 1988 Nov;13(11):15-6, 19-20, 22 passim, NCBI PMID: 3231355.
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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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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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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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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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