| Secondary Sex Ratio among Women Exposed to Diethylstilbestrol in Utero Lauren A. Wise,1 Julie R. Palmer,1 Elizabeth E. Hatch,2 Rebecca Troisi,3,4 Linda Titus-Ernstoff,3 Arthur L. Herbst,5 Raymond Kaufman,6 Kenneth L. Noller,7 and Robert N. Hoover4 1Slone Epidemiology Center, Boston University, Boston, Massachusetts, USA; 2Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA; 3Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, USA; 4Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA; 5Department of Obstetrics and Gynecology, University of Chicago, Chicago, Illinois, USA; 6Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas, USA; 7Department of Obstetrics and Gynecology, New England Medical Center, Boston, Massachusetts, USA Abstract
Background: Diethylstilbestrol (DES) , a synthetic estrogen widely prescribed to pregnant women during the mid-1900s, is a potent endocrine disruptor. Previous studies have suggested an association between endocrine-disrupting compounds and secondary sex ratio. Methods: Data were provided by women participating in the National Cancer Institute (NCI) DES Combined Cohort Study. We used generalized estimating equations to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the relation of in utero DES exposure to sex ratio (proportion of male births) . Models were adjusted for maternal age, child's birth year, parity, and cohort, and accounted for clustering among women with multiple pregnancies. Results: The OR for having a male birth comparing DES-exposed to unexposed women was 1.05 (95% CI, 0.95–1.17) . For exposed women with complete data on cumulative DES dose and timing (33%) , those first exposed to DES earlier in gestation and to higher doses had the highest odds of having a male birth. The ORs were 0.91 (95% C, 0.65–1.27) for first exposure at ≥ 13 weeks gestation to < 5 g DES ; 0.95 (95% CI, 0.71–1.27) for first exposure at ≥ 13 weeks to ≥ 5 g ; 1.16 (95% CI, 0.96–1.41) for first exposure at < 13 weeks to < 5 g ; and 1.24 (95% CI, 1.04–1.48) for first exposure at < 13 weeks to ≥ 5 g compared with no exposure. Results did not vary appreciably by maternal age, parity, cohort, or infertility history. Conclusions: Overall, no association was observed between in utero DES exposure and secondary sex ratio, but a significant increase in the proportion of male births was found among women first exposed to DES earlier in gestation and to a higher cumulative dose. Key Words: diethylstilbestrol, estrogens, endocrine-disrupting chemicals, females, sex ratios. Environ Health Perspect 115:1314–1319 (2007) . doi:10.1289/ehp.10246 available via http://dx.doi.org/ [Online 28 June 2007]
Address correspondence to L.A. Wise, Slone Epidemiology Center, 1010 Commonwealth Ave., 4th Floor, Boston, MA 02215 USA. Telephone: (617) 734-6006. Fax: (617) 738-5119. E-mail: lwise@slone.bu.edu This study was supported by grants N01-CP-21168, N01-CP-51017, and N01-CP-01289 from the National Cancer Institute. The authors declare they have no competing financial interests. Received 9 March 2007 ; accepted 28 June 2007.
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