Menstrual and reproductive Characteristics of Women whose Mothers were exposed in Utero to DES

DES Follow-up Study Summary

We examined menstrual and reproductive characteristics in a unique cohort consisting of the daughters of women prenatally exposed (or not) to Diethylstilbestrol DES (i.e., the third generation). The menstrual and reproductive characteristics of 793 third generation women were assessed by mailed questionnaires. The study showed a comparable average age of menarche (12.6 years) in the daughters of prenatally DES-exposed and unexposed women. The daughters of the exposed women reached menstrual regularity later compared to the daughters of the unexposed, and were more likely to report irregular menstrual periods, odds ratio. A possible association between mothers’ DES exposure and daughters’ infertility was compatible with chance. For the most part, daughters of the prenatally DES-exposed and unexposed had similar reproductive outcomes, but daughters of exposed women had fewer live births than the unexposed. The high risk of reproductive problems seen in women exposed prenatally to DES was not observed in their daughters, but most third generation women have not yet attempted to start their families. Consequently, further follow-up is needed to assess their reproductive health.

2006 Study 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.

Sources

• Menstrual and reproductive characteristics of women whose mothers were exposed in utero to diethylstilbestrol (DES),NCBI, PMID: 16723367, 2006 Aug;35(4):862-8. Epub 2006 May 24. Full text Oxford Journals Medicine & Health International Journal of Epidemiology link.
• NCI, DES Follow-up Study Published Papers.

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