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Journal Article 
Serum dioxin concentrations and age at menarche 
Warner, M; Samuels, S; Mocarelli, P; Gerthoux, PM; Needham, L; Patterson, DG, Jr; Eskenazi, B 
Environmental Health Perspectives
ISSN: 0091-6765
EISSN: 1552-9924 
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
dioxin; endocrine disruptors; environmental exposures; epidemiology;
menarche; puberty; 2,3,7,8-tetrachlorodibenzo-p-dioxin 
Accidents, Occupational 
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