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IJE Advance Access published online on May 24, 2006
International Journal of Epidemiology, doi:10.1093/ije/dyl106
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Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2006; all rights reserved.
Accepted April 24, 2006

Original paper

Menstrual and reproductive characteristics of women whose mothers were exposed in utero to diethylstilbestrol (DES)

Linda Titus-Ernstoff 1 *, Rebecca Troisi 2, Elizabeth E. Hatch 3, Lauren A. Wise 4, Julie Palmer 4, Marianne Hyer 5, Raymond Kaufman 6, Ervin Adam 7, William Strohsnitter 8, Kenneth Noller 8, Arthur L. Herbst 9, Jennifer Gibson-Chambers 1, Patricia Hartge 10, and Robert N. Hoover 10

1 Department of Community and Family Medicine, Dartmouth Medical School, and the Norris Cotton Cancer Center, Lebanon, NH 03756, USA
2 Department of Community and Family Medicine, Dartmouth Medical School, and the Norris Cotton Cancer Center, Lebanon, NH 03756, USA; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA
3 Department of Epidemiology and Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA
4 Slone Epidemiology Center, Boston University School of Public Health, Boston, MA 02215, USA
5 Information Management Services, Rockville, MD 20852, USA
6 Department of Obstetrics and Gynecology, Methodist Hospital, Houston, TX 77030, USA
7 Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, USA
8 Department of Obstetrics and Gynecology, New England Medical Center, Boston, MA 02111, USA
9 Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL 60637, USA
10 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA

* To whom correspondence should be addressed.
Linda Titus-Ernstoff, E-mail: Linda.Titus-Ernstoff{at}Dartmouth.edu


  Abstract

Background In women, prenatal exposure to diethylstilbestrol (DES) is associated with adult reproductive dysfunction. The mouse model, which replicates many DES outcomes, suggests DES causes epigenetic alterations, which are transmissable to daughters of prenatally exposed animals. We report menstrual and reproductive characteristics in a unique cohort comprising daughters of women exposed prenatally to DES.

Methods Menstrual and reproductive outcomes and baseline characteristics were assessed by mailed questionnaire in 793 women whose mothers had documented information regarding in utero DES exposure.

Results Mean age at menarche was 12.6 years in both groups, but daughters of the exposed women attained menstrual regularization later (mean age of 16.2 years vs. 15.8 years; P = 0.05), and were more likely to report irregular menstrual periods, odds ratio (OR) = 1.54 [95% confidence interval (95% CI 1.02-2.32)]. A possible association between mothers' DES exposure and daughters' infertility was compatible with chance, age, and cohort adjusted OR = 2.19 (95% CI 0.95-5.07). We found limited evidence that daughters of the exposed had more adverse reproductive outcomes, but daughters of exposed women had fewer live births (1.6) than the unexposed (1.9) (P = 0.005).

Conclusions The high risk of reproductive dysfunction seen in women exposed to DES in utero was not observed in their daughters, but most women in our cohort have not yet attempted to start their families, and further follow-up is needed to assess their reproductive health. Our findings of menstrual irregularity and possible infertility in third-generation women are preliminary but compatible with speculation regarding transgenerational transmission of DES-related epigenetic alterations in humans.

Keywords: Diethylstilbestrol; prenatal exposure; maternal exposure; menstruation; reproductive histories; infertility; epigenetic alternations.
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Related articles in Int. J. Epidemiol.:

Commentary: Prenatal exposure to diethylstilbestrol (DES): a continuing story
John A. McLachlan
Int. J. Epidemiol. 2006 10.1093/ije/dyl140. [Abstract]  

Commentary: Prenatal exposure to diethylstilbestrol (DES): a continuing story
John A. McLachlan
Int. J. Epidemiol. 2006 10.1093/ije/dyl140. [Abstract]  



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