子宫内暴露于己烯雌酚的女性的不良健康后果。

Adverse health outcomes in women exposed in utero to diethylstilbestrol.

机构信息

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.

出版信息

N Engl J Med. 2011 Oct 6;365(14):1304-14. doi: 10.1056/NEJMoa1013961.

DOI:10.1056/NEJMoa1013961

PMID:21991952

Abstract

BACKGROUND

Before 1971, several million women were exposed in utero to diethylstilbestrol (DES) given to their mothers to prevent pregnancy complications. Several adverse outcomes have been linked to such exposure, but their cumulative effects are not well understood.

METHODS

We combined data from three studies initiated in the 1970s with continued long-term follow-up of 4653 women exposed in utero to DES and 1927 unexposed controls. We assessed the risks of 12 adverse outcomes linked to DES exposure, including cumulative risks to 45 years of age for reproductive outcomes and to 55 years of age for other outcomes, and their relationships to the baseline presence or absence of vaginal epithelial changes, which are correlated with a higher dose of, and earlier exposure to, DES in utero.

RESULTS

Cumulative risks in women exposed to DES, as compared with those not exposed, were as follows: for infertility, 33.3% vs. 15.5% (hazard ratio, 2.37; 95% confidence interval [CI], 2.05 to 2.75); spontaneous abortion, 50.3% vs. 38.6% (hazard ratio, 1.64; 95% CI, 1.42 to 1.88); preterm delivery, 53.3% vs. 17.8% (hazard ratio, 4.68; 95% CI, 3.74 to 5.86); loss of second-trimester pregnancy, 16.4% vs. 1.7% (hazard ratio, 3.77; 95% CI, 2.56 to 5.54); ectopic pregnancy, 14.6% vs. 2.9% (hazard ratio, 3.72; 95% CI, 2.58 to 5.38); preeclampsia, 26.4% vs. 13.7% (hazard ratio 1.42; 95% CI, 1.07 to 1.89); stillbirth, 8.9% vs. 2.6% (hazard ratio, 2.45; 95% CI, 1.33 to 4.54); early menopause, 5.1% vs. 1.7% (hazard ratio, 2.35; 95% CI, 1.67 to 3.31); grade 2 or higher cervical intraepithelial neoplasia, 6.9% vs. 3.4% (hazard ratio, 2.28; 95% CI, 1.59 to 3.27); and breast cancer at 40 years of age or older, 3.9% vs. 2.2% (hazard ratio, 1.82; 95% CI, 1.04 to 3.18). For most outcomes, the risks among exposed women were higher for those with vaginal epithelial changes than for those without such changes.

CONCLUSIONS

In utero exposure of women to DES is associated with a high lifetime risk of a broad spectrum of adverse health outcomes. (Funded by the National Cancer Institute.).

摘要

背景

在 1971 年之前，有几百万女性在子宫内接触到了己烯雌酚（DES），这种药物是给她们的母亲用的，以防止妊娠并发症。一些不利的结果与这种接触有关，但它们的累积效应尚不清楚。

方法

我们结合了三个在 20 世纪 70 年代开始的研究的数据，并对 4653 名子宫内暴露于 DES 的女性和 1927 名未暴露的对照组进行了长期随访。我们评估了 12 种与 DES 暴露有关的不良结果的风险，包括生殖结果到 45 岁和其他结果到 55 岁的累积风险，以及它们与阴道上皮变化的存在或不存在的关系，这些变化与更高剂量和更早的宫内 DES 暴露有关。

结果

与未暴露的女性相比，DES 暴露的女性的累积风险如下：不孕，33.3%对 15.5%（风险比，2.37；95%置信区间[CI]，2.05 至 2.75）；自然流产，50.3%对 38.6%（风险比，1.64；95%CI，1.42 至 1.88）；早产，53.3%对 17.8%（风险比，4.68；95%CI，3.74 至 5.86）；妊娠中期流产，16.4%对 1.7%（风险比，3.77；95%CI，2.56 至 5.54）；异位妊娠，14.6%对 2.9%（风险比，3.72；95%CI，2.58 至 5.38）；子痫前期，26.4%对 13.7%（风险比，1.42；95%CI，1.07 至 1.89）；死产，8.9%对 2.6%（风险比，2.45；95%CI，1.33 至 4.54）；早绝经，5.1%对 1.7%（风险比，2.35；95%CI，1.67 至 3.31）；宫颈上皮内瘤变 2 级或以上，6.9%对 3.4%（风险比，2.28；95%CI，1.59 至 3.27）；40 岁及以上乳腺癌，3.9%对 2.2%（风险比，1.82；95%CI，1.04 至 3.18）。对于大多数结果，有阴道上皮变化的暴露女性的风险高于没有这种变化的女性。