Adverse Health Outcomes in Women Exposed In Utero to Diethylstilbestrol
Adverse Health Outcomes in Women Exposed In Utero to Diethylstilbestrol
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DOI：
10.1056/nejmoa1013961
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发表时间：
2011-10-06
影响因子：
158.5
通讯作者：
Troisi, Rebecca
中科院分区：
文献类型：
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作者：
Hoover, Robert N.;Hyer, Marianne;Troisi, Rebecca
1971年以前，数百万妇女在子宫内接触到己烯雌酚（DES），给她们的母亲服用DES以防止妊娠并发症。几个不良后果已被链接到这样的曝光，但其累积效应并不很好理解。METHODSWe结合数据从三项研究开始于20世纪70年代，持续长期随访的4653名妇女暴露在子宫内DES和1927未暴露的控制。我们评估了与DES暴露相关的12种不良结局的风险，包括45岁以下生殖结局的累积风险和55岁以下其他结局的累积风险，以及它们与阴道上皮变化的基线存在或不存在的关系，阴道上皮变化与子宫内较高剂量和较早暴露于DES相关。与未接触者相比，不孕症患者分别为33.3%和15.5%，（风险比，2.37; 95%置信区间[CI]，2.05 - 2.75）;自然流产，50.3% vs. 38.6%（风险比，1.64; 95% CI，1.42 - 1.88）;早产，53.3% vs. 17.8%（风险比，4.68; 95% CI，3.74 - 5.86）;中期妊娠丢失，16.4% vs. 1.7%（风险比，3.77; 95% CI，2.56 - 5.54）;异位妊娠，14.6% vs. 2.9%（风险比，3.72; 95% CI，2.58 - 5.38）;先兆子痫，26.4% vs. 13.7%（风险比1.42; 95% CI，1.07 - 1.89）;死产，8.9% vs. 2.6%（风险比，2.45; 95% CI，1.33 - 4.54）;绝经早期，5.1% vs. 1.7%（风险比，2.35; 95% CI，1.67 - 3.31）; 2级或以上宫颈上皮内瘤变，6.9% vs. 3.4%（风险比，2.28; 95%CI，1.59至3.27）; 40岁或以上的乳腺癌，3.9%对2.2%（风险比，1.82; 95%CI，1.04至3.18）。对于大多数结果，暴露的妇女之间的风险是较高的阴道上皮细胞的变化比那些没有这样的changes.CONCLUSIONSIn子宫内暴露的妇女DES是与一个高的终身风险的广泛的不良健康后果。（由国家癌症研究所资助。
BACKGROUNDBefore 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.METHODSWe 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.RESULTSCumulative 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.CONCLUSIONSIn 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.)