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Reprod Toxicol. 2019 Mar;84:32-38. doi: 10.1016/j.reprotox.2018.12.008. Epub 2018 Dec 27.

Reproductive and hormone-related outcomes in women whose mothers were exposed in utero to diethylstilbestrol (DES): A report from the US National Cancer Institute DES Third Generation Study.

Author information

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.

KEYWORDS:

DES; Diethylstilbestrol; Epigenetic; Granddaughters; Intergenerational; Third generation women

PMID:
30594671
PMCID:
PMC6382553
[Available on 2020-03-01]
DOI:
10.1016/j.reprotox.2018.12.008
[Indexed for MEDLINE]

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