Treffers P E, Hanselaar A G, Helmerhorst T J, Koster M E, van Leeuwen F E
Universitair Medisch Centrum St Radboud, afd. Pathologie, Nijmegen.
Ned Tijdschr Geneeskd. 2001 Apr 7;145(14):675-80.
Since the 1940s, diethylstilbestrol (DES) has been administered to about three million pregnant women in the United States and in the Netherlands, between 1947 and 1975, to about 220,000. The most important consequences described are: for DES mothers an increased risk of mammary carcinomas and for DES daughters a 1 in 1000 chance of clear cell adenocarcinoma (CCAC) as well as an increased risk of (pre)malignant abnormalities of the stratified epithelium in the vagina and cervix. In addition to this, DES daughters frequently have developmental disorders of the cervix and corpus uteri. In connection with this fertilisation disorders have been described as well as unfavourable outcomes of pregnancy: more ectopic pregnancies, abortion and premature birth. DES sons exhibit an increased frequency of several benign abnormalities of the genitalia. The DES problem continues to be an important issue. The entire cohort of DES mothers is in the age group with a high risk of mammary carcinoma. The youngest DES daughters will be of childbearing age for at least another 15 years; the risk of ectopic pregnancies and pre-term labour is increased. The oldest DES daughters are now reaching postmenopausal age. The incidence of CCAC of the vagina and cervix in the population is bimodal, with a second peak at older age. It is still unknown if at this age DES daughters will have an increased incidence of these malignancies. From animal experiments it becomes clear that DES administration to pregnant mice results in an increased incidence of genital tumours not only in the second generation but also in the third. This has yet to be investigated in humans and deserves special attention. The legally imposed destruction of patient files after a period of ten years is a serious threat to patient care and scientific investigation, notably in obstetrics and child medicine.
自20世纪40年代以来，己烯雌酚（DES）已在美国约300万孕妇中使用，在荷兰，1947年至1975年间约有22万孕妇使用过。所描述的最重要后果是：对于服用DES的母亲，患乳腺癌的风险增加；对于DES女儿，患透明细胞腺癌（CCAC）的几率为千分之一，以及阴道和宫颈分层上皮（癌前）恶性异常的风险增加。除此之外，DES女儿经常出现宫颈和子宫体发育障碍。与此相关的还有受精障碍以及不良妊娠结局的描述：更多的宫外孕、流产和早产。DES儿子的生殖器出现几种良性异常的频率增加。DES问题仍然是一个重要问题。服用DES的母亲整个队列都处于乳腺癌高危年龄组。最年轻的DES女儿至少还有15年才到育龄；宫外孕和早产的风险增加。最年长的DES女儿现在正步入绝经后年龄。人群中阴道和宫颈CCAC的发病率呈双峰分布，在老年时有第二个高峰。目前尚不清楚在这个年龄DES女儿这些恶性肿瘤的发病率是否会增加。从动物实验中可以清楚地看到，给怀孕小鼠服用DES不仅会导致第二代而且会导致第三代生殖器肿瘤发病率增加。这一点在人类中还有待研究，值得特别关注。法律规定在十年后销毁患者档案对患者护理和科学研究构成严重威胁，尤其是在妇产科和儿童医学领域。
