Warner Marcella, Samuels Steven, Mocarelli Paolo, Gerthoux Pier Mario, Needham Larry, Patterson Donald G, Eskenazi Brenda
School of Public Health, University of California at Berkeley, Berkeley, California 94720-7380, USA.
Environ Health Perspect. 2004 Sep;112(13):1289-92. doi: 10.1289/ehp.7004.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a widespread environmental contaminant, is associated with delays in pubertal development in animal studies. On 10 July 1976, as a result of a chemical explosion, residents of Seveso, Italy, experienced the highest levels of TCDD exposure experienced by a human population. Twenty years later, we initiated the Seveso Women's Health Study (SWHS), a retrospective cohort study of female residents of the most contaminated areas, to determine whether the women were at higher risk for reproductive disease. We examined the association of TCDD serum levels, based on measurements in serum collected soon after the explosion, with reported age at menarche among the 282 SWHS women who were premenarcheal at the time of the explosion. We found no change in risk of onset of menarche with a 10-fold increase in TCDD (e.g., 10-100 ppt; hazard ratio = 0.95; 95% confidence interval, 0.83-1.09; p-value for trend = 0.46). When TCDD levels were categorized, there was also no evidence of a dose-response trend (p = 0.65). In summary, we found that individual serum TCDD measurements are not significantly related to age at menarche among women in the SWHS cohort. The women in this study experienced substantial TCDD exposure during the postnatal but prepubertal developmental period. Given that animal evidence suggests in utero exposure has the most significant effect on onset of puberty, continued follow-up of the offspring of the SWHS cohort is important.
2,3,7,8-四氯二苯并对二恶英（TCDD）是一种广泛存在的环境污染物，在动物研究中，它与青春期发育延迟有关。1976年7月10日，由于一场化学爆炸，意大利塞韦索的居民经历了人类群体中最高水平的TCDD暴露。二十年后，我们启动了塞韦索妇女健康研究（SWHS），这是一项对污染最严重地区女性居民的回顾性队列研究，以确定这些女性是否患生殖疾病的风险更高。我们根据爆炸后不久采集的血清测量值，研究了282名在爆炸时处于月经初潮前的SWHS女性中TCDD血清水平与报告的月经初潮年龄之间的关联。我们发现，TCDD增加10倍（例如，10 - 100皮克/升）时，月经初潮开始的风险没有变化（风险比 = 0.95；95%置信区间，0.83 - 1.09；趋势p值 = 0.46）。当对TCDD水平进行分类时，也没有剂量反应趋势的证据（p = 0.6）。总之，我们发现，在SWHS队列中的女性中，个体血清TCDD测量值与月经初潮年龄没有显著相关性。本研究中的女性在出生后但青春期前的发育阶段经历了大量的TCDD暴露。鉴于动物研究证据表明子宫内暴露对青春期开始有最显著的影响，对SWHS队列后代的持续随访很重要。
