Medical Conditions among Adult Offspring prenatally exposed to DiEthylStilbestrol

DES Follow-up Study Summary

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DES side-effects on Offspring exposed in Utero.

Concern about the possible impact of estrogen-like substances found in the environment on a range of health conditions has spurred research in this area. Diethylstilbestrol (DES) is an example of an endocrine-disruptor i.e., chemicals that interfere with the body’s hormone system. While prenatal exposure to DES is known to increase risks of vaginal or cervical cancer and poor reproductive outcomes in women, and abnormalities in the urinary and genital tracts in men information on non-reproductive medical conditions are lacking.

We studied the associations between prenatal DES exposure and the occurrence of cardiovascular disease, diabetes, osteoporosis and related conditions among 5,590 exposed and unexposed daughters and 2,657 exposed and unexposed sons in the NCI Combined DES Follow-up Study. The associations took into account the participants’ birth year, sex, weight adjusted for height, smoking status, alcohol use, educational status, number of general physical examinations in the past 5 years, and study site.

Comparing participants exposed prenatally to DES with those who were not exposed, there were increases in the risk of developing cardiovascular disease (27%), heart attacks (28%), hypertension (14%), and high cholesterol (12%). In addition, the risks of developing diabetes, coronary artery disease, osteoporosis and fractures were elevated, but these findings were possibly due to chance. The associations of DES and the medical conditions did not differ by dose and timing of DES exposure, nor, in the women, by presence or absence of vaginal epithelial changes (a marker of DES host susceptibility).

This study raises the possibility that prenatal DES exposure is associated with several common medical conditions in adulthood, although there is the possibility that our results are explained by differences in the reporting of conditions by the exposed and unexposed participants, or by other factors related to both the conditions and DES exposure status that were not accounted for in the study, such as dietary intake and physical activity. We plan to continue to study these associations by obtaining medical records to confirm the diagnoses in the current round of the study.

DES Info commented: ” DES Exposure estimated hazard ratios and their associated 95% confidence intervals for the associations between prenatal DES exposure and the occurrence of cardiovascular disease, diabetes, osteoporosis, and related conditions among 5590 female and 2657 male offspring followed from 1994 through 2006, adjusted for birth year, cohort, sex, body mass index, smoking status, alcohol use, education, and number of general physical examinations in the past 5 years “.

2013 Study Abstract:

BACKGROUND:
Diethylstilbestrol (DES), a synthetic estrogen that was used in pregnancy, is a prototype endocrine-disrupting chemical. Although prenatal exposure to DES is known to increase risks of vaginal/cervical adenocarcinoma and adverse reproductive outcomes in women, and urogenital anomalies in men, data on nonreproductive medical conditions are lacking.

METHODS:
We estimated hazard ratios and their associated 95% confidence intervals for the associations between prenatal DES exposure and the occurrence of cardiovascular disease, diabetes, osteoporosis, and related conditions among 5590 female and 2657 male offspring followed from 1994 through 2006, adjusted for birth year, cohort, sex, body mass index, smoking status, alcohol use, education, and number of general physical examinations in the past 5 years.

RESULTS:
Comparing persons exposed prenatally to DES with those who were not exposed, the hazard ratios were 1.21 (95% confidence interval = 0.96-1.54) for diabetes, 1.27 (1.00-1.62) for all cardiovascular disease, 1.18 (0.88-1.59) for coronary artery disease, 1.28 (0.88-1.86) for myocardial infarction, 1.12 (1.02-1.22) for high cholesterol, 1.14 (1.02-1.28) for hypertension, 1.24 (0.99-1.54) for osteoporosis, and 1.30 (0.95-1.79) for fractures. The associations did not differ by dose and timing of DES exposure, nor, in the women, by the presence or absence of vaginal epithelial changes (a marker of DES host susceptibility).

CONCLUSIONS:
These data raise the possibility that prenatal exposure to DES is associated with several common medical conditions in adulthood, although differential reporting by DES status and residual confounding cannot be ruled out. Further follow-up should assess these findings with validated outcomes and seek to understand the biological mechanisms.

Sources:

  • Medical conditions among adult offspring prenatally exposed to diethylstilbestrol,NCBI, PMID: 23474687, 2013 May;24(3):430-8. doi: 10.1097/EDE.0b013e318289bdf7. Full text link.
  • NCI, DES Follow-up Study Published Papers.
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