Summary of findings from courtesy of

The DES Follow-Up Study investigates the long-term health consequences associated with exposure to diethylstilbestrol (DES). Since 1992, the National Cancer Institute, in collaboration with research centers throughout the United States has been conducting the DES Follow-Up Study of more than 21,000 mothers, daughters, and sons.

Prenatal DES Exposure and Common Adult Chronic Diseases.

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.

Click here to read the Pub Med article

Study of Genetic Markers in DES Exposed Daughters

Environmental scientists consider DES the ultimate model for studying the impact of exposure to environmental endocrine disruptors (chemicals that interfere with the body’s hormone system) during fetal development. Over three decades of studies in laboratory animals have raised multiple possible biologic effects that could be responsible for the poor health outcomes seen in DES exposed daughters, with one of the most promising indicating that prenatal exposure to DES causes persistent epigenetic changes (epigenetic changes occur in the cells during fetal development and typically turn on or off genes). In addition, some studies in laboratory animals indicate a possible effect of DES on hormone concentrations in women who were prenatally exposed.

Researchers at the National Cancer Institute, Boston University and Dartmouth Medical School are attempting to study whether genetic changes and hormone concentrations differ between women who were and were not prenatally exposed to DES. Initially, a small pilot study of 60 women (30 who were exposed to DES and 30 who were not) is planned. Blood samples will be drawn from women participating in our long-term DES Follow-up Study of the health effects of DES exposure. If the study is successful (if women can be recruited and blood samples obtained), we plan to study this question in a larger group of women. The findings of this pilot study may have profound implications for the ways in which endocrine disruption in the fetus influences human health in later life.


What are the cancer rates for persons who have been exposed to DES in utero?

In 1971, a strong association between DES use in pregnancy and the occurrence of vaginal clear cell adenocarcinoma (CCA) in exposed daughters was reported. A study published in 1998 found that DES daughters showed no increase in risk of cancer overall or for specific types of cancer, except CCA. The daughters in this study were, however, on average, in their late 30s and had not reached the age at which we expect cancer to occur so we are continuing to monitor these women. Overall, men exposed to DES in utero have not been found to have an increased risk of cancer. The risk for specific types of cancer in men, such as testicular or prostate cancer, is unclear and we are continuing to study it.


Does DES cause infertility?

A study published in 2001, based on the National Cooperative Diethylstlbestrol Adenosis Study (DESAD) and another cohort of DES exposed and unexposed daughters, found that DES daughters were more likely to have had premature births, miscarriages, and ectopic pregnancies. In addition, the study indicated that the risk of infertility was higher in DES daughters than in unexposed women, and that the increased risk of infertility was mainly due to uterine or tubal problems. A comprehensive review of the health outcomes of DES exposed daughters published in October 2011 reports that exposed daughters were 2.37 times as likely as unexposed women to have infertility, and that exposed women who became pregnant at least once were 1.64 times as likely to have spontaneous abortion and 4.68 times as likely to have a preterm birth. These adverse events are common in the general population, and even more likely among exposed daughters.


Does DES cause early menopause?

Researchers have found that daughters whose mothers were given DES during pregnancy are two times more likely to have menopause prior to age 45, compared to women who were not exposed to DES. They estimate that 3% of DES-exposed women have experienced early menopause due to their exposure to DES.


Should I use hormone therapy if I have been exposed to DES in utero? Is it safe?

Each woman should discuss this important question with her doctor. Although studies have not shown that the use of birth control pills or hormone replacement therapy is unsafe for DES-exposed daughters, some doctors believe these women should avoid these medications because they contain estrogen.


Does DES exposure cause autoimmune diseases like Hashimoto’s thyroiditis, lupus, rheumatoid arthritis, or multiple sclerosis?

We studied autoimmune disease in depth and published our findings in 2010. They are summarized in the 2010 DES newsletter. In short, we observed no differences in overall autoimmune disease rates between women who were and were not DES-exposed. There was also no difference in lupus and optic neurosis rates between the two groups. With regard to rheumatoid arthritis (RA), our study corroborated findings of an earlier study and we observed a possible increase in RA among DES-exposed women but this was confined to women under the age of 45. There was no overall increase in RA between exposed and unexposed women. There were too few cases if idiopathic thrombocytopenia purpura (ITP) to determine whether or not it is elevated among DES-exposed women. In addition, there was no significant difference in multiple sclerosis rates between women who and were not DES-exposed. This was based on a preliminary review of early data from the DES Follow-up Study. As a result, it was not studied as extensively as the other four aforementioned autoimmune diseases.


I am having heart trouble and want to know if this may have been caused by exposure to DES?

Currently, there is no evidence that DES exposure during pregnancy or in utero is associated with cardiovascular or coronary heart disease. Analyses are underway to study causes of death, including cardiovascular and coronary heart disease, in mothers who took DES. The majority of women who were exposed to DES have not yet reached the ages during which heart disease is common. In the future, however, it will be possible to address this question.


Can exposure to DES before birth influence psychosexual characteristics of those individuals who were exposed?

A study published in 2003 found little support for the hypothesis that in utero exposure to DES influences the psychosexual characteristics (the likelihood of ever having been married, age at first intercourse, number of sexual partners, and having had a same-sex sexual partner in adulthood) of adult men and women.


Are there any problems with the grandchildren of women who were given DES while pregnant? (i.e., the third generation)

Several reports have examined DES grandchildren for possible abnormalities. For the granddaughters, these studies indicate that the age of first menstruation is not affected by DES, but that DES-exposed granddaughters have a greater likelihood of menstrual irregularity. In a small clinical study that included pelvic exams, researchers found no evidence of DES-related changes in the granddaughters of women given DES during pregnancy. A study of cancer outcomes in the granddaughters and grandsons showed no overall increased risk of cancer in either gender. An excess of ovarian cancer was seen in the granddaughters of exposed women, but the number of cases was small, so the evidence is considered preliminary. Investigations in Holland and France have shown a higher risk of hypospadias (a genitourinary anomaly) in the grandsons of DES-exposed women, but DES exposure was not verified in these studies. An analysis of NCI data suggested an increased risk of hypospadias in DES-exposed grandsons, but the finding was not conclusive. A study conducted in Holland found an increased risk of tracheo-esophageal fistula in granddaughters, but this also was not seen in the NCI data.


Are there any problems with the grandsons of women who were given DES during pregnancy? (i.e., the third generation)

As noted above, several studies have noted possible increased risk of hypospadius in grandsons of women who took DES during their pregnancy. However most of the studies had methodological limitations and the association was inconclusive in the NCI data, where DES exposure was verified.


My mother took DES with my sibling, but I am the one who is having all the problems. Do you know if there is any relationship between my mother taking DES before she was pregnant with me and all the problems that I am having?

At this time, we have no reason to expect that unexposed siblings of individuals who were exposed to DES in utero would experience any adverse effects because there is no biological evidence that this is possible.


What steps do I take to find out if I am a DES daughter?

It has been estimated that 5 to 10 million people were exposed to DES during pregnancy. Many of these people are not aware that they were exposed. A woman who was pregnant between 1938 and 1971 and had problems or a history of problems during pregnancy may have been given DES or a similar drug. Women who think they used a hormone such as DES during pregnancy, or people who think that their mother used DES during pregnancy, can contact the attending physician or the hospital where the delivery took place to request a review of the medical records. If any pills were taken during pregnancy, obstetrical records should be checked to determine the name of the drug. Mothers and children have a right to this information.
However, finding medical records after a long period of time can be difficult. If the doctor has retired or died, another doctor may have taken over the practice, as well as the records. The county medical society or health department may know where the records have been stored. Some pharmacies keep records for a long time and can be contacted regarding prescription dispensing information. Military medical records are kept for 25 years. In many cases, however, it may be impossible to determine whether DES was used.


I was exposed to DES before birth. How often should I have a colposcopic examination?

When we first began our DES studies, we suggested that a colposcopic examination be done each year. After several years it became obvious that only those women who had changes in the lining of the vagina or cervix (about 30%) needed to have the procedure every year. However, you should continue to have pelvic examinations and PAP smears on a yearly basis. If you have had an abnormal pap smear in the past, or have one at any time, you should follow your physician’s advice. Your gynecologist should be able to provide information on whether you have had previous vaginal epithelial changes if you are unsure of your previous history.