Intrauterine exposure to diethylstilbestrol: Long-term effects in humans (original) (raw)
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Journal of the Medical Association of the State of Alabama, 1977
In 1971 a link between maternal diethylstilbestrol (DES) therapy during pregnancy and the later occurrence of clear-cell adenocarcinoma of the vagina in female offspring exposed to the drug in utero was 1st reported. Patients ranged from 7 to 28 years of age at the time of diagnosis. A registry now has data on almost 300 such cases. The registry address is: MARP Room 303 5841 Maryland Avenue Chicago Illinois 60637. Because DES-type hormones were not given to some of the mothers of these cancer patients other factors also play a role in the etiology of these cancers. In all cases when dates are precise the drug was given before the 18th week of gestation. Cancers related to DES therapy have not been reported in male offspring. Doses and duration of therapy have varied widely. As many as 2 million mothers may have been so treated. Benign vaginal adenosis has also been present in cancer cases and in 1/3 of other exposed patients. Cervical ectropion has been observed in most cases. Othe...
Cancer risk in women prenatally exposed to diethylstilbestrol
International Journal of Cancer, 2007
Prenatal diethylstilbestrol (DES) exposure is associated with excess risks of clear cell adenocarcinoma (CCA), and breast cancer in older women. Whether overall cancer risk is also elevated is unclear. Total and site-specific cancer risks were evaluated in the DES Combined Cohort Follow-up Study using age-and calendaryear specific standardized incidence rate ratios (SIR), and ageadjusted incidence rate ratios (RR) comparing DES exposed and unexposed women. A total of 143 and 49 cancer cases occurred in 97,831 and 34,810 person-years among the exposed and unexposed, respectively. There was no overall excess risk among exposed women when compared with external rates (SIR 1.01; 95% confidence interval [CI] 0.86-1.2). The overall RR comparing exposed with unexposed women was 1.32 (95% CI 0.94-1.8). Breast cancer risk was elevated only among women over 40 years (RR 1.83; 95% CI 1.1-3.2). The CCA SIR among exposed women was nearly 40, and the estimated attack rate through age 39 was 1.6/1,000 women. CCA incidence decreased by over 80% after age 25 when compared with 20-24 years. Excluding CCA and breast cancer, the overall RR was 1.21 (95% CI 0.74-2.0). DES was not associated with excess risks of either endometrial or ovarian cancer. These data suggest that the DES associated increase in CCA incidence remains elevated through the reproductive years. There was no consistent evidence of risk excesses for cancers other than CCA, and breast cancer in older women. Given that the population is still young, continued follow-up is necessary to assess the overall carcinogenic impact of prenatal DES exposure. ' 2007 Wiley-Liss, Inc.
Cancer Risk in Women Exposed to Diethylstilbestrol In Utero
JAMA, 1998
Context.-The association between in utero exposure to diethylstilbestrol (DES) and clear cell adenocarcinoma (CCA) of the vagina and cervix is well known, yet there has been no systematic study of DES-exposed daughters to determine whether they have an increased risk of other cancers. As many as 3 million women in the United States may have been exposed to DES in utero.
Commentary: Prenatal exposure to diethylstilbestrol (DES): a continuing story
International Journal of Epidemiology, 2006
Developmental exposure to diethylstilbestrol elicits demethylation of estrogen-responsive lactoferrin gene in mouse uterus. Cancer Res 1997;57:4356-59. 28 Couse JF, Dixon D, Yates M et al. Estrogen receptor-a knockout mice exhibit resistance to the developmental effects of neonatal diethylstilbestrol exposure on the female reproductive tract.
Long-term cancer risk in women given diethylstilbestrol (DES) during pregnancy
British Journal of Cancer - BRIT J CANCER, 2001
From 1940 through the 1960s, diethylstilbestrol (DES), a synthetic oestrogen, was given to pregnant women to prevent pregnancy complications and losses. Subsequent studies showed increased risks of reproductive tract abnormalities, particularly vaginal adenocarcinoma, in exposed daughters. An increased risk of breast cancer in the DES-exposed mothers was also found in some studies. In this report, we present further follow-up and a combined analysis of two cohorts of women who were exposed to DES during pregnancy. The purpose of our study was to evaluate maternal DES exposure in relation to risk of cancer, particularly tumours with a hormonal aetiology. DES exposure status was determined by a review of medical records of the Mothers Study cohort or clinical trial records of the Dieckmann Study. Poisson regression analyses were used to estimate relative risks (RR) and 95% confidence intervals (CI) for the relationship between DES and cancer occurrence. The study results demonstrated ...
Reproductive outcomes in men with prenatal exposure to diethylstilbestrol
Fertility and Sterility, 2005
Objective: To examine prenatal diethylstilbestrol (DES) exposure in relation to male reproductive outcomes. Design: Prospective observational study. Setting: Participants were identified through record review, clinical trial participation, or an obstetrics clinic. Patient(s): A total of 1,085 DES-exposed and 1,047 unexposed men. Intervention(s): Participants were exposed prenatally to DES through the mother's obstetrics care or clinical trial participation. Main Outcome Measure(s): Infertility; never fathering a pregnancy or live birth; number of pregnancies or live births fathered. Result(s): We found little evidence that prenatal DES exposure affects the likelihood of never fathering a pregnancy or live birth, or influences the mean number of fathered pregnancies or live births. Our data suggest that DES-exposed men are slightly more likely to experience infertility (relative risk [RR] ϭ 1.3, 95% confidence interval [CI] ϭ 1.0-1.6). The DES dose and gestational timing did not influence infertility or the number of pregnancies or live births fathered, but results were inconsistent for dose effects on the likelihood of never fathering a pregnancy or a live birth. Conclusion(s): Prenatal DES exposure may be associated with a slightly increased risk of having an infertility experience, but does not increase the likelihood of never fathering a pregnancy or a live birth, or the number of pregnancies or live births fathered.
2006
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 5 0.05), and were more likely to report irregular menstrual periods, odds ratio (OR) 5 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 5 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 5 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.
Cancer Risk in Men Exposed In Utero to Diethylstilbestrol
JNCI Journal of the National Cancer Institute, 2001
Background: An association between prenatal diethylstilbestrol (DES) exposure and cancer in men, especially testicular cancer, has been suspected, but findings from case-control studies have been inconsistent. This study was conducted to investigate the association between prenatal DES exposure and cancer risk in men via prospective follow-up. Methods: A total of 3613 men whose prenatal DES exposure status was known were followed from 1978 through 1994. The overall and sitespecific cancer incidence rates among the DES-exposed men were compared with those of the unexposed men in the study and with population-based rates. The relative rate (RR) was used to assess the strength of the association between prenatal DES exposure and cancer development. All statistical tests were two-sided. Results: Overall cancer rates among DES-exposed men were similar to those among unexposed men (RR = 1.07; 95% confidence interval [CI] = 0.58 to 1.96) and to national rates (RR = 0.99; 95% CI = 0.65 to 1.44). Testicular cancer may be elevated among DES-exposed men, since the RRs for testicular cancer were 3.05 (95% CI = 0.65 to 22.0) times those of unexposed men in the study and 2.04 (95% CI = 0.82 to 4.20) times those of males in the population-based rates. The higher rate of testicular cancer in the DES-exposed men is, however, also compatible with a chance observation. Conclusions: To date, men exposed to DES in utero do not appear to have an increased risk of most cancers. It remains uncertain, however, whether prenatal DES exposure is associated with testicular cancer. [J Natl Cancer Inst 2001;93:545-51]
2001
Objectives: Women exposed prenatally to diethylstibestrol (DES) have an excess risk of clear-cell adenocarcinoma of the vagina and cervix, but the eect on the incidence of squamous neoplasia is uncertain. The purpose of the current study was to evaluate the long-term risk of developing high-grade squamous neoplasia of the genital tract among women exposed prenatally to DES. Methods: A cohort comprising 3899 DES-exposed and 1374 unexposed daughters was followed for 13 years (1982± 1995) for pathology-con®rmed diagnoses of high-grade squamous intraepithelial neoplasia (HSIL) of the genital tract. Poisson regression analysis was used to compute relative risks (RR) and 95% con®dence intervals (95% CI), adjusting for age, calendar year, and other covariates. Results: The RR (95% CI) among DES-exposed versus unexposed, based on 111 cases of high-grade disease, was 2.1 (1.2±3.8). Adjustment for screening history estimated by the number of years since the last Pap smear had little eect. Risk estimates were higher with earlier intrauterine exposure; the RR (95% CI) for exposure within 7 weeks of the last menstrual period was 2.8 (1.4±5.5). Only two cases of invasive squamous cervical cancer occurred in total, precluding separate analysis. Conclusions: The ®ndings support an association between in-utero DES exposure and high-grade squamous neoplasia, although a role for more intensive screening among DES-exposed women in the production of this excess could not be completely ruled out.