These DES abnormalities may not be as traumatic as others depicted on this site but they are equally difficult for the DES affected woman. DES congenital anomalies can make the sexual experience very difficult and painful. In addition, some of the DES cellular changes can mimic vaginal adenocarcinoma and expose the DES daughter to additional examinations, Pap smears, biopsies and surgeries that otherwise would not have been needed. There is much known about DES anatomical mutations and the interested reader is invited to review some of the medical literature on this subject. Some of these studies date to the early 1970s when the first associations between DES usage in mothers and gynecological abnormalities in DES daughters were first being described.
Because of the abnormal embryological development of the vagina and cervix in DES daughters, synechiae can develop. These are abnormal areas of fibrosis or scar tissue development that limit the elasticity and proper function of the female genital tract. As a result, the entire area becomes much less distensible and DES daughters may note dyspareunia or pain during sexual intercourse. According to Stillman, who wrote a comprehensive review in 1982, structural cervical and vaginal abnormalities have been reported in 22-58% of DES-exposed women (1).
These include cervical collars, hoods, protuberances, sulci (grooves), annular or transverse ridges and frank cervical hypoplasia. These anomalies can result in an abnormal mucoid discharge. When practitioners have attempted to perform cryosurgery on these abnormal areas, severe cervical stenosis or narrowing has been reported. Since the internal lining of the lower female genital tract is disturbed by intrauterine DES exposure, the female sexual experience later on is often painful and frustrating.
Vaginal adenosis of the tuboendometrial type, which has been a precursor to frank adenocarcinoma, may require multiple examinations, tests, biopsies and cryosurgeries. Robboy et al reported in 1984 two cohorts of women who were diagnosed with these histological changes after known DES exposure (21). The first group of 20 DES exposed women had undergone radical hysterectomy with or without vaginectomy for clear cell adenocarcinoma of the cervix or vagina, respectively.
In this group, benign tuboendometrial adenosis was seen in 95% and atypical tuboendometrial adenosis was seen in 80% of cases directly next to the invasive cancer. In a related group of 47 cases with the same diagnosis of clear cell adenocarcinoma, but with less complete pathological sectioning, 36 (77%) were also associated with adenosis immediately adjacent to the cancer. This clear progression from benign adenosis to atypical adenosis to invasive cancer is a paradigm that is commonly recognized with other malignancies, especially colon cancer. Based on these findings, these authors suggested that even more aggressive surveillance and biopsies were warranted in DES daughters since the adenocarcinomas could be multifocal and that areas of malignant potential extended beyond the limits of the obvious cancer.
Robboy and colleagues also described a DES mouse model in 1982 that described the alterations in the female reproductive tract and accurately predicted what is seen clinically in DES exposed women (22). Intact reproductive tracts were transplanted from human embryos and fetuses from 5-17.7 weeks of age into nude mice that were given either a placebo or DES. Those genital tracts developed remarkably differently under the influence of DES. Normally, the paired embryonic Mullerian ducts fuse into a single uterovaginal tract or canal, the uterine and Fallopian tube mesenchyme (supporting structure) differentiates into inner endometrial and outer myometrial (muscular) layers and there is plication or folding of the tubal endometrial mucosal linings. The vagina develops into a stratified squamous barrier lining. Finally, there is uterine gland formation that allows for implantation of a fertilized ovum. Under the influence of DES, glandular epithelium or adenosis is found in the vagina, the growth of the upper genital tract is stunted and the inner and outer linings of the uterine body and Fallopian tubes fail to separate. All of these findings are markedly abnormal and have been seen in DES exposed patients.
1. Stillman R.J. In Utero Exposure to Diethylstilbestrol: Adverse Effects on the Reproductive Tract and Reproductive Performance in Male and Female Offspring. Am J. Obstet. & Gynec. 142:902, April 1982.
21. Robboy S. J. et al. Atypical Vaginal Adenosis and Cervical Ectropion. Cancer. 54:869-875, September 1984.
22. Robboy S.J. et al. Normal Development of the Human Female Reproductive Tract and Alterations Resulting from Experimental Exposure to Diethylstilbestrol. Hum Pathol. 13:190-198, 1982.