Linda Titus1, Elizabeth E Hatch2, Keith M Drake3, Samantha E Parker2, Marianne Hyer4, Julie R Palmer5, William C Strohsnitter6, Ervin Adam7, Arthur L Herbst8, Dezheng Huo9, Robert N Hoover10, Rebecca Troisi10. 1. Departments of Epidemiology and Pediatrics, Geisel School of Medicine at Dartmouth, and the Norris Cotton Cancer Center, HB 7927, One Medical Center Drive, Lebanon, NH 03756, United States; Department of Pediatrics, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, United States. Electronic address: Linda.Titus@Dartmouth.edu. 2. Department of Epidemiology, Boston University School of Public Health, Boston, MA 02118, United States. 3. Department of Pediatrics, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, United States. 4. Information Management Services, Rockville, MD 20852, United States. 5. Slone Epidemiology Center, Boston University School of Public Health, Boston, MA, 02215, United States. 6. Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, United States. 7. Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX, 77030, United States. 8. Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL, 60637, United States. 9. Department of Public Health Sciences, University of Chicago, Chicago, IL, 60637, United States. 10. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, United States.
Abstract
BACKGROUND: Animal studies suggest that prenatal exposure to diethylstilbestrol (DES) causes epigenetic alterations in primordial germ cells that affect the next generation, but human studies are sparse. METHODS: We assessed hormonally mediated outcomes in third generation women whose mothers were prenatally DES-exposed and unexposed. RESULTS: Compared to the unexposed, DES-exposed third generation women had an increased risk of irregular menses and amenorrhea; the respective prevalence ratios and 95% confidence intervals (CI) in follow-up data were 1.32 (95% CI: 1.10, 1.60) and 1.26 (95% CI: 1.06, 1.49); associations were more apparent in third generation women whose prenatally DES-exposed mothers were affected by vaginal epithelial changes. The follow-up data also indicated an association with preterm delivery (relative risk (RR): 1.54; 95% CI: 1.35, 1.75). CONCLUSION: DES third generation women may have an increased risk of irregular menstrual cycles, amenorrhea, and preterm delivery, consistent with inter-generational effects of endocrine disrupting chemical exposure in humans.
BACKGROUND: Animal studies suggest that prenatal exposure to diethylstilbestrol (DES) causes epigenetic alterations in primordial germ cells that affect the next generation, but human studies are sparse. METHODS: We assessed hormonally mediated outcomes in third generation women whose mothers were prenatally DES-exposed and unexposed. RESULTS: Compared to the unexposed, DES-exposed third generation women had an increased risk of irregular menses and amenorrhea; the respective prevalence ratios and 95% confidence intervals (CI) in follow-up data were 1.32 (95% CI: 1.10, 1.60) and 1.26 (95% CI: 1.06, 1.49); associations were more apparent in third generation women whose prenatally DES-exposed mothers were affected by vaginal epithelial changes. The follow-up data also indicated an association with preterm delivery (relative risk (RR): 1.54; 95% CI: 1.35, 1.75). CONCLUSION:DES third generation women may have an increased risk of irregular menstrual cycles, amenorrhea, and preterm delivery, consistent with inter-generational effects of endocrine disrupting chemical exposure in humans.
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