The majority of these mothers who said they did not take DES were indeed DES positive by written records…
The written obstetric records of maternal exposure to diethylstilbestrol (DES) were used as a criterion standard and compared with the DES exposure history recalled by mothers of women with vaginal, cervical, or indeterminable vaginal/exocervical clear cell adenocarcinoma.
Among cervical cases, the sensitivity of maternal recall was 50% (N = 2), and its specificity was 100%. Among vaginal and vaginal/exocervical cases, this sensitivity was 72%; specificity was 60%; and the majority of these mothers who said they did not take DES were DES positive by written records.
Thus investigators should avoid using maternal recall alone to measure DES exposure. Among subjects for whom written maternal obstetric records were available, 88% of vaginal cases and 46% of cervical cases were DES positive. The authors conclude that few cases of vaginal clear cell adenocarcinoma should occur in young women as the cohort of women exposed in utero to DES continues to age, whereas cases of cervical origin may continue to occur.
In this 1980 study, the difference in pregnancy outcomes between the DES daughters and the unexposed is highly significant
Reproductive histories were compared for 226 diethylstilbestrol-exposed daughters and 203 DES-unexposed daughters whose mothers participated in a double-blind evaluation 27 years before. Irregular menstruation was slightly more common among the exposed (10%) than among the unexposed (4%). Nineteen of the exposed and only four of the unexposed had primary infertility. Among those at risk, 86% of the unexposed and 67% of the exposed had become pregnant. The reasons for these differences are not known. Comparison of evaluable first pregnancy outcome revealed full-term live birth to be more common among the unexposed (85%) than the exposed (47%). Premature live birth was experienced by 22% of the exposed but only 7% of the unexposed. Nonviable outcomes of stillbirth, neonatal death, miscarriage and ectopic pregnancy occurred in 31% of the exposed and 8% of the unexposed. The difference in pregnancy outcomes between the groups is highly significant. The DES-exposed with transverse cervicovaginal ridges were more likely to experience a nonviable outcome. Overall 82% of the exposed and 93% of the unexposed had at least one live offspring.
The majority of DES-exposed women do not perform monthly breast-self examinations
DES Follow-up Study Summary
The purpose of this paper was to determine if women exposed in utero to Diethylstilbestrol (DES) are more likely than unexposed women to receive recommended or additional breast cancer screening examinations.
Data from the study cohort were used to assess the degree of recommended compliance of breast cancer screenings was found in 3,140 DES exposed and 826 unexposed women. Participants were enrolled at four sites: Houston, Boston, Rochester, and Los Angeles. The data from the mailed questionnaires that included the reported frequency from 1990 through 1994 of breast-self examinations (BSEs), clinical breast examinations (CBEs), and mammograms was analyzed.
The results showed that the DES-exposed women exceeded annual recommendations for CBEs among women without a history of benign breast disease compared with unexposed women. There were no other statistically significant differences between exposed and unexposed women who reported performing BSEs, CBEs (less than 40 years of age), and mammographies, regardless of benign breast disease history.
Although this study showed that the majority of DES-exposed women receive breast cancer screenings at least at recommended intervals, it also showed that over two thirds do not perform monthly BSEs. It is recommended that Future efforts should be focused on further educating this and other at-risk populations through mailed reminders and during patient consultations on the benefits of screening examinations.
2009 Study Abstract
To determine if women exposed in utero to diethylstilbestrol (DES) are more likely than unexposed women to receive recommended or additional breast cancer screening examinations.
1994 Diethylstilbestrol-Adenosis (DESAD) cohort data are used to assess the degree of recommended compliance of breast cancer screenings found in 3140 DES-exposed and 826 unexposed women. Participants were enrolled at four sites: Houston, Boston, Rochester, and Los Angeles. Logistic regression modeling was used to analyze mailed questionnaire data that included reported frequency over the preceding 5 years (1990-1994) of breast-self examinations (BSEs), clinical breast examinations (CBEs), and mammograms.
DES-exposed women exceeded annual recommendations for CBEs (aOR 2.20, 95% CI, 1.04-4.67) among women without a history of benign breast disease (BBD) compared with unexposed women. There were no other statistically significant differences between exposed and unexposed women who reported performing BSEs, CBEs (<40 years of age), and mammographies, regardless of BBD history.
The majority of DES-exposed women receive breast cancer screenings at least at recommended intervals, but over two thirds do not perform monthly BSEs. Future efforts should be focused on further educating this and other at-risk populations through mailed reminders and during patient consultations on the benefits of screening examinations.
Breast cancer screening in women exposed in utero to diethylstilbestrol,NCBI, PMID: 19361323, 2009 Apr;18(4):547-52. doi: 10.1089/jwh.2007.0580. Full text PMC2857514.
A total of 143 exposed women and 49 unexposed women in the DES Combined Cohort Follow-up Study were diagnosed with cancer as of 2001.
Compared with breast cancer rates in the general US population, there was no overall higher risk among DES exposed women. Comparing exposed with unexposed women within the study, there was about a 30% increase in cancer risk but this finding could be due to chance. As reported in a previous article (Palmer 2006), breast cancer risk was elevated but only among women over 40 years of age. Exposed women had a risk of CCA that was nearly 40% higher than the general population, however; the incidence of CCA decreased substantially after age 25 compared with women 20 to 24 years old. Excluding CCA and breast cancer, the higher risk of cancer among the DES exposed women was about 20%, a result that could be due to chance. DES was not associated with higher risks of either endometrial or ovarian cancer. These data suggest that the DES associated increase in CCA rates remains elevated through the reproductive years. There was no consistent evidence of a higher risk for cancers other than CCA, and breast in older women.
Given that the population is still young, continued follow-up is necessary to assess the overall cancer risk associated with prenatal DES exposure.
Cancer risk in women prenatally exposed to diethylstilbestrol,NCBI, PMID: 17390375, 2007 Jul 15;121(2):356-60.
In utero exposure to DES is associated with a 50 % higher risk of preeclampsia
DES Follow-up Study Summary
Women exposed to Diethylstilbestrol (DES) in utero experience a greater risk of adverse reproductive events including infertility, ectopic pregnancies, spontaneous pregnancy losses and premature births. These complications may in part be due to prenatal effects of DES on the structure of the uterus or cervix. Preeclampsia, a common pregnancy complication characterized by maternal hypertension, and high levels of uric acid and protein, frequently involves the placenta not entirely attaching to the mother’s endometrium (implantation). DES-associated uterine abnormalities and possible alterations in immune function may adversely affect successful implantation.
The hypothesis that prenatal DES exposure is associated with preeclampsia risk was previously addressed in a small case-control study that reported a greater than two-fold risk in women who reported a history of DES exposure compared with those who did not. We used data from the National Cancer Institute DES Combined Cohorts Follow-up Study to readdress this issue. A total of 285 preeclampsia cases (210 exposed and 75 unexposed) occurred in 7313 live births (4759 DES exposed and 2554 unexposed). Prenatal DES exposure was associated with nearly a 50% elevation in preeclampsia risk in the daughters’ pregnancies. Taking into account differences in DES exposed and unexposed women in preeclampsia risk factors including age at the pregnancy, number of pregnancies, education, smoking, a measure of body fatness, and year of preeclampsia diagnosis, the risk was slightly lower, about 40%. The increased risk of preeclampsia associated with prenatal DES exposure was concentrated among women who developed preeclampsia in their first pregnancy (80% higher risk), those who were exposed to DES before 15 weeks of pregnancy (57% higher risk) and those who were treated with magnesium sulfate (over two times the risk). Among DES-exposed women who had a prior hysterosalpingogram (a procedure that allows physicians to view the reproductive organs), preeclampsia prevalence was higher in those with uterine abnormalities (12.4%) than in those without (7.7%). Our data suggest that prenatal DES exposure is associated with a slightly elevated risk of preeclampsia that is possibly due to a higher prevalence of uterine abnormalities in DES daughters.
Women exposed to diethylstilbestrol (DES) in utero experience a greater risk of adverse reproductive events including infertility, ectopic gestations, spontaneous pregnancy losses and premature births. These complications may in part be mediated through teratogenic effects, namely the structural uterine and cervical abnormalities that have been associated with in utero DES exposure. Preeclampsia, a common pregnancy complication characterized by maternal hypertension, hyperuricemia, and proteinuria frequently involves shallow placentation. Placental establishment requires cytotrophoblast invasion of the underlying stroma and blood vessels of the maternal endometrium, a process involving immune and angiogenic mechanisms. DES-associated uterine abnormalities and possible alterations in immune function (4-7) may adversely affect successful implantation.
The hypothesis that prenatal DES exposure is associated with preeclampsia risk was previously addressed in a small case-control study that reported a greater than two-fold risk in women who reported a history of DES exposure compared with those who did not.
2007 Study Abstract
To assess whether preeclampsia risk is elevated in pregnancies of diethylstilbestrol (DES)-exposed daughters.
This study used data from the National Cancer Institute DES Combined Cohorts Follow-up Study. A total of 285 preeclampsia cases (210 exposed and 75 unexposed) occurred in 7,313 live births (4,759 DES exposed and 2,554 unexposed). Poisson regression analysis estimated relative risks and 95% confidence intervals (CI) for preeclampsia adjusted for age at the index pregnancy, parity, education, smoking, body mass index, year of diagnosis, and cohort.
In utero DES exposure was associated with nearly a 50% elevation in preeclampsia risk. Adjustment for preeclampsia risk factors attenuated the relative risk slightly (1.42, 95% CI 1.04-1.94). The excess risk with DES was concentrated among women who developed preeclampsia in their first pregnancies (relative risk 1.81, 95% CI 1.17-2.79), who were exposed before 15 weeks of gestation (relative risk 1.57, 95% CI 1.11-2.23), and who were treated with magnesium sulfate (relative risk 2.10, 95% CI 0.82-5.42). Among DES-exposed women who had a prior hysterosalpingogram, preeclampsia prevalence was higher in those with uterine abnormalities (12.4%) than in those without (7.7%).
These data suggest that in utero exposure to DES is associated with a slightly elevated risk of preeclampsia, and that one possible biological mechanism involves uterine abnormalities.
Preeclampsia risk in women exposed in utero to diethylstilbestrol,NCBI, PMID: 17601905, 2007 Jul;110(1):113-20.
Pregnancy outcomes in DES-exposed women are worse than those in unexposed women
2000 Study Abstract
To evaluate long-term pregnancy experiences of women exposed to diethylstilbestrol (DES) in utero compared with unexposed women.
This study was based on diethylstilbestrol-exposed daughters, the National Collaborative Diethylstylbistrol Adenosis cohort and the Chicago cohort, and their respective nonexposed comparison groups. Subjects who could be traced were sent a detailed questionnaire in 1994 that contained questions on health history, including information on pregnancies and their outcomes. We reviewed 3373 questionnaires from exposed daughters and 1036 questionnaires from unexposed women.
The response rate was 88% among exposed and unexposed women. Diethylstilbestrol-exposed women were less likely than unexposed women to have had full-term live births and more likely to have had premature births, spontaneous pregnancy losses, or ectopic pregnancies. Full-term infants were delivered in the first pregnancies of 84.5% of unexposed women compared with 64. 1% of exposed women identified by record review (relative risk [RR] 0.76, confidence interval [CI] 0.72, 0.80). Preterm delivery of first births occurred in 4.1% of unexposed compared with 11.5% of exposed women, and ectopic pregnancies in 0.77% of unexposed compared with 4.2% of exposed women. Spontaneous abortion was reported in 19.2% of DES-exposed women compared with 10.3% in control women (RR 2.00, CI 1.54, 2.60). According to complete pregnancy histories (many women had more than one pregnancy), preterm births were more common in DES-exposed women (19.4% exposed versus 7.5% unexposed (RR 2.93 CI 2.23, 3.86). Second-trimester spontaneous pregnancy losses were more common in DES-exposed women (6.3% versus 1.6%; RR 4.25, CI 2.36, 7.66). More first-trimester spontaneous abortions occurred in DES-exposed women than in controls (RR 1.31, CI 1.13, 1.53), and DES-exposed women had at least one ectopic pregnancy more often than unexposed women (RR 3.84, CI 2.26, 6.54).
Pregnancy outcomes in DES-exposed women were worse than those in unexposed women.
Currently, over 400 cases of clear cell adenocarcinoma of the vagina and cervix occurring in females born after 1940 have been accessioned into the Registry for Research on Hormonal Transplacental Carcinogenesis. Cases have been identified throughout the United States as well as Australia, Canada, Mexico, and Europe. Intrauterine exposure to DES and similar nonsteroidal estrogens have been uncovered in about two-thirds of the cases with an available maternal history. A peak in the age incidence curve of the DES-related cases has been observed at about 19 years with the age range being 7-30 years. The five-year survival for 400 patients has been 80%. Numerous nonmalignant epithelial changes have been observed. It appears that there has not been an increase in the occurrence of premalignant or malignant squamous cell lesions among the DES exposed. Premature birth has been more common among DES-exposed women. For those in whom there is evidence of a midpregnancy loss or premature ripening of the cervix during pregnancy, a cerclage procedure has been effective in producing a desirable outcome.
Higher infertility rate and abnormalities found in the DES Daughters
Infertility was examined among 343 diethylstilbestrol-exposed and 303 unexposed daughters whose mothers participated in an evaluation of diethylstilbestrol use during pregnancy 35 years ago. Of the married individuals who were not using contraception and who were actively trying to conceive, a greater proportion of diethylstilbestrol-exposed women than unexposed subjects experienced primary infertility (33% versus 14%, p less than 0.001). Among those with primary infertility, abnormal hysterosalpingograms were observed in 46% of the diethylstilbestrol-exposed group and in none of the unexposed group (p less than 0.02), while tubal abnormalities were found in 42% of the exposed and in none of the unexposed (p = 0.02). First pregnancies were achieved by 40 (58%) women exposed to diethylstilbestrol and 18 (64%) unexposed subjects. Twenty-four (60%) of the exposed women and 15 (83%) of the unexposed individuals who conceived had a live-born infant who survived. The estimated cumulative rate of first pregnancy was 16% for the exposed group and 36% for the unexposed group at 12 months after the diagnosis of primary infertility (p less than 0.05).
Age-incidence and risk of diethylstilbestrol-related clear cell adenocarcinoma of the vagina and cervix
This study was based on cases accessioned in the Registry of Clear Cell Adenocarcinoma of the Genital Tract in Young Females to ascertain the incidence of diethylstilbestrol (DES)-related cancers by age and year of birth. For accuracy in estimating the size of the reference population for the incidence rates, calculations were restricted to 127 white residents of the United States who were exposed prenatally to DES or other nonsteroidal synthetic estrogens. The disease is exceedingly rare prior to age 14 when the incidence rate begins to rise rapidly. The incidence peaks at age 19 (median 19.2 years) and then drops precipitately. Thus, DES-related clear cell adenocarcinoma is unusual in that nearly all cancers have been diagnosed in a narrow age range of 10 years (14 to 23 years). Women born in 1951 to 1953 have higher incidence rates than those born in the previous or subsequent three-year period. This suggests that the prevalence of pregnancy-related use of DES was at a peak in the early 1950’s. The cumulative risk of this type of genital cancer, through age 24, for DES-exposed female subjects is estimated to be in the range of 0.14 to 1.4 per thousand. The wide limits are due to the fact that the number of young women exposed is not known precisly. The low risk of disease and the narrow age range of the cases, relative to the long latency period, suggest that DES is an incomplete carcinogen. Other factors, possibly related to puberty, may be involved in the causation of this disease.
American journal of obstetrics and gynecology, 1981
Information on reproductive history, gynecologic operations, and examinations was analyzed for 338 diethylstilbestrol (DES)-exposed and 298 unexposed women whose mothers participated in an evaluation of DES use in pregnancy 28 years ago. A history of infrequent menses (less often than every 36 days) was reported more commonly by the exposed women (32%) than by the unexposed women (15%) and the mean duration of menstrual flow was also less. A greater number of exposed women than unexposed women experienced primary infertility (53 versus 19). The reasons for these differences are not currently known. Comparison of the outcomes of first pregnancies showed a higher proportion of premature births, spontaneous abortions, and ectopic pregnancies in the exposed women (P less than 0.001). The difference in the occurrence of ectopic pregnancies was statistically significant (8 versus 0; P less than 0.005). An adverse pregnancy outcome was more likely in DES-exposed women with cervicovaginal ridges. However, when the outcome of all pregnancies were considered, 81% of the exposed women had at least one living child. More exposed women than unexposed women had gynecologic surgical procedures, which may, in part, be due to the increased medical surveillance of the exposed group. The spectrum of diseases at operation in both groups was similar. Adnexal masses and pelvic inflammatory disease were more commonly reported among the exposed women while the occurrence of endometriosis in both groups was similar. For the exposed women who had been examined at the Chicago Lying-In Hospital over a 4-year period, epithelial changes in the vagina had disappeared in 32% and cervicovaginal ridges had disappeared in 57%.