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

Linda Titus; Elizabeth E Hatch; Keith M Drake; Samantha E Parker; Marianne Hyer; Julie R Palmer; William C Strohsnitter; Ervin Adam; Arthur L Herbst; Dezheng Huo; Robert N Hoover; Rebecca Troisi

doi:10.1016/j.reprotox.2018.12.008

Reproductive Endocrinology · Ovarian Hormones

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

Titus L, Hatch EE, Drake KM, Parker SE, Hyer M, Palmer JR, Strohsnitter WC, Adam E, Herbst AL, Huo D, Hoover RN, Troisi R

Published March 2019 Reproductive toxicology (Elmsford, N.Y.)

DOI 10.1016/j.reprotox.2018.12.008 PMID 30594671 PMC PMC6382553

RRM Academy Synopsis

Daughters of DES-exposed women report more irregular cycles

A cohort study found that women whose mothers had prenatal DES exposure reported irregular cycles more often. At follow-up, about 25 out of 100 exposed women reported them, against about 19 out of 100 unexposed. Amenorrhea (no period for six weeks or more) and preterm delivery were also reported more often at follow-up.

Key Findings

Irregular cycles at follow-up: 94 of 381 exposed women (24.7%) and 54 of 280 unexposed women (19.3%); prevalence ratio 1.32 (95% CI: 1.10, 1.60). Baseline ratio: 1.22 (95% CI: 1.12,1.33).
Amenorrhea at follow-up: 67 of 381 exposed women (17.6%) and 42 of 280 unexposed women (15.0%); prevalence ratio 1.26 (95% CI: 1.06, 1.49). Baseline ratio: 1.22 (95% CI: 0.85, 1.75).
Preterm delivery at follow-up, among women who had been pregnant: 22 of 182 exposed (12.1%) and 11 of 138 unexposed (8.0%); risk ratio 1.54 (95% CI: 1.35, 1.75).
Mothers with vaginal epithelial changes (a marker of early and high DES exposure): daughters' baseline ratio for irregular cycles was 1.30 (95% CI: 1.17, 1.46); without them, 1.04 (95% CI: 0.74, 1.46).
Age at first menses was similar: an average of 12.5 in exposed women and 12.7 in unexposed women (MD: −0.20; 95% CI: −0.57, 0.16).

Interpretation

This cohort study compared women whose mothers did and did not have prenatal DES exposure. Medical records or physician notes verified each mother's exposure status. Participants reported their own outcomes on questionnaires. Most were white and under thirty at baseline. Irregular cycles showed an association at baseline and at follow-up. Preterm delivery showed an association in the follow-up data, with a baseline ratio of 1.31 (95% CI: 0.81,2.10). The authors state that this young group needs more follow-up to judge infertility and ectopic pregnancy.

RRM Context

Restorative reproductive medicine seeks the cause of an irregular cycle. In this cohort, a grandmother's DES use was linked to irregular cycles in her granddaughters. The authors say this matters for other drugs and chemicals that disrupt hormones.

Our editorial summary of this paper, not the article's abstract.

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.

Topics

Reproductive Endocrinology › Ovarian Hormones › Estrogen · Lifestyle and Environment › Environmental Exposures › Endocrine Disrupting Chemicals · Menstrual Cycle › Cycle Disorders › Amenorrhea

Linda Titus, Elizabeth E Hatch, Keith M Drake, Samantha E Parker, Marianne Hyer, Julie R Palmer, William C Strohsnitter, Ervin Adam, Arthur L Herbst, Dezheng Huo, Robert N Hoover, Rebecca Troisi

L Titus, Liz Hatch, Beth Hatch, Betsy Hatch, E Hatch, K Drake, Sam Parker, S Parker, M Hyer, J Palmer, Bill Strohsnitter, Will Strohsnitter, Billy Strohsnitter, W Strohsnitter, E Adam, A Herbst, D Huo, Bob Hoover, Rob Hoover, Bobby Hoover, R Hoover, Becky Troisi, R Troisi

PMID 30594671 30594671 DOI 10.1016/j.reprotox.2018.12.008 10.1016/j.reprotox.2018.12.008 Titus et al. 2019, Titus 2019

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

Daughters of DES-exposed women report more irregular cycles

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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