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DES Follow-up Study Background

1938
 DES first produced
Mid-1940s to early 1970s
 Women widely used DES as a treatment for threatened miscarriages
Mid-1970s
 Participants recruited into DES studies across the nation
1992
 NCI-DES Follow-up Study began
1994
 1st questionnaires mailed
1997
 2nd questionnaires and 1st newsletter mailed
1999
 2nd newsletter mailed
2000
 1st questionnaires mailed to grdanddaughters
2001
 3rd questionnaires and 3rd newsletter mailed
2004
 DES web site developed
2005
 4th newsletter mailed Web site launched
2006
 4th questionnaires mailed
2009
 2nd questionnaires mailed to granddaughters
2010
 5th newsletter mailed
2011
 5th questionnaires mailed and web version available for completion on website
2015
 6th newsletter mailed
2016
 6th questionnaires mailed and web version available for completion on website
The National Cancer Institute (NCI) Combined DES Cohorts Follow-up Study is a nationwide research study following more than 21,000 women and men to learn as much as possible about the long-term health effects of DES exposure. The NCI study is the largest ongoing research study on long-term health and DES exposure. Five research centers in the United States carry out the DES Follow-up Study, coordinated by NCI. Leaders in DES research and education are responsible for the study and are dedicated to increasing scientific and medical knowledge about DES exposure. The research team includes physicians, epidemiologists, researchers, and DES advocates and educators. The following provides more background information about DES and the DES Followup Study.

The following provides more background information about DES and the DES Followup Study.

  What is DES
  Reasons to Study DES
  The History of DES Research at NCI
  NCI’s DES Follow-up Study
      DESAD Cohort
      Women’s Health Study Cohort
      Mayo Clinic Cohort
      Dieckmann Cohort
      Horne Cohort
  How the DES Follow-up Study is Conducted
  Priorities and Challenges of the DES Follow-up Study
  Scientific researchers, center coordinators and DES advocates

What is DES?

Diethylstilbestrol (DES) is a non-steroidal estrogen, and the first estrogen pill. It was produced in 1938 and was widely used from the mid-1940s until the early 1970s as a treatment for women who were at risk of miscarriages. It is estimated that millions of Americans (mothers, daughters, and sons) may have been exposed to DES. In 1971, data demonstrated a connection between a mother’s use of DES during pregnancy and the occurrence of cancer of the vagina in her daughters. Subsequently, DES has been associated with several other health effects, including an increased frequency of problems of the reproductive tract, changes in the tissue of the vagina, infertility and poor pregnancy outcomes in daughters.

Reasons to Study DES

The most important reason to study DES is to provide DES-exposed people and medical professionals with information about the long-term health effects of DES exposure.

The study is also an important source of scientific information. DES is often used as a way of studying how chemicals that act like or interfere with hormones in the body affect health. Although numerous cancer-causing agents are known to pass from the placenta to the fetus in animals, DES is unique because it is the only agent known to do the same in humans.

Finally, the study of DES may aid in understanding the effects of hormones, in general, during the development of the fetus.

The History of DES Research at NCI

The NCI study is funded by Congress because of passage of the DES Research and Education legislation.

Congress has passed two bills requiring research on DES exposure, and two National Institutes of Health (NIH)-sponsored workshops on DES were held in 1992 and 1999 to make research recommendations. These recommendations included the following:

Continue to monitor the people participating in studies of DES for cancer risk, particularly among daughters as they approach menopause and among DES-exposed sons;

Assess the impact of and risks associated with exposure to other hormones such as hormone replacement therapy in DES-exposed mothers and daughters;

Study whether DES-exposed women and men will develop non-reproductive conditions.

NCI’s DES Follow-up Study

In 1992, NCI, together with researchers at five research centers, began a long-term study of individuals exposed to DES. Participants were initially drawn from eight different medical centers and consisted of five individual cohorts (groups of people being studied). These cohorts are the DESAD cohort, Women’s Health Study cohort, Mayo Clinic cohort, Dieckmann cohort, and Horne Cohort. In order for the study findings to be valid, enrollment in the study is limited to participants who have been part of existing cohorts. Currently, it is not possible for the DES Follow-up Study to accept new participants. Five cohorts (groups of people being studied) make up the DES Follow- Up Study.
  • DESAD (Diethylstilbestrol Adenosis Project) Cohort
    The largest number of DES-exposed daughters were identified from the DESAD cohort, which enrolled more than 4,000 exposed and 1,000 unexposed daughters. Beginning in 1975 enrollment took place at Baylor College of Medicine, Gundersen Clinic, Massachusetts General Hospital, the Mayo Clinic, and the University of Southern California. Sisters of exposed participants and other women who were not related to the DES-exposed participants were included in the study as a comparison group. The primary goal of the study was to provide yearly clinical examinations for the daughters to ascertain their risk of reproductive problems. Exposed and unexposed daughters underwent identical examinations through l983. They were mailed yearly questionnaires from 1984 to 1989 to document their reproductive and medical history. All participants from the DESAD cohort were included in the DES Follow-up Study if their exposure to DES was known and they had responded to at least one mailed questionnaire between 1984 and 1989.

  • Women’s Health Study Cohort
    The Women's Health Study started in 1981 to study breast cancer in DES-exposed mothers. More than 3,000 women exposed to DES at any time during pregnancy and 3,000 unexposed women were identified through a review of prenatal records from 1940-60 at the Boston Lying-in Hospital, the Mayo Clinic, Dartmouth Medical School (Mary Hitchcock Hospital), and a private obstetrical practice in Portland, Maine. Prior to the DES Follow-up Study, these mothers were sent three mailed questionnaires during the 1980s, and medical records were collected when participants reported that they had cancer. Daughters and sons of these women had not been studied previously. Two of the three centers tried to enroll daughters and sons from the Women’s Health Study, whether or not they were exposed to DES, into the DES Follow-up Study. More than 1,000 daughters and 1,000 sons have been added to the NCI study through these efforts.
  • Mayo Clinic Cohort
    This cohort is the largest cohort of sons included in the DES Follow-up Study. It was identified by reviewing prenatal records of women who gave birth at Mayo Clinic hospitals between 1939 and 1961. Men who were exposed to DES and others who were not exposed were asked to participate. The medical records of these sons were studied to determine if DES exposure was related to an increased risk of infertility, problems with the genitals or urinary tract, and cancer. About one-third of both the exposed and unexposed sons also had a physical examination at the Mayo Clinic during the early 1980s.
  • Dieckmann Cohort
    The DES Follow-up Study also includes mothers and their daughters and sons from the Dieckmann cohort. These women were enrolled in a clinical trial at the University of Chicago from 1950-52 to determine whether DES was effective at preventing pregnancy loss. In the mid-1970s, the Dieckmann mothers were located and recruited for a telephone interview study. Attempts to locate the children of the mothers who participated in the Dieckmann trial began around the same time. Between 1974 and 1976, exposed and unexposed sons were examined for genital problems. This cohort was last contacted in 1992 when questionnaires focusing on fertility were obtained from 253 exposed and 241 unexposed sons. Contact was off and on with the Dieckmann cohort mothers and children until the start of the DES Follow-up Study.
  • Horne Cohort
    The Horne cohort includes mothers who were treated with DES by Dr. Herbert Horne, an infertility physician in Boston, and their exposed and unexposed children. Beginning in 1971, Dr. Horne periodically sent questionnaires to these participants.

How the DES Follow-up Study is Conducted

The DES Follow-Up Study participants are sent questionnaires requesting information about their recent health history. In 1994, 1997, 2001, 2006, 2011 and 2016 questionnaires were mailed to or telephone interviews conducted with participants in all the cohorts. Web questionnaires were made available starting in 2006. Deaths were identified through these contacts. Information on diseases such as cancer, benign breast and gynecologic tumors, precancerous conditions of the cervix, autoimmune diseases (like rheumatoid arthritis), psychiatric disorders, and genito-urinary conditions (such as epidydimal cysts) among the sons was collected. Information was collected also on general cancer risk factors and known breast, ovarian, and endometrial cancer risk factors, in addition to demographic variables (e.g., age, education), and health screening behaviors. This information has been and continues to be analyzed statistically to understand the relationship between DES and health outcomes. This is done by comparing the occurrence of disease in participants who were exposed to DES with those who were not exposed to DES.

Priorities and Challenges of the DES Follow-up Study

Our primary goal is to measure new cases of cancer and deaths from cancer, especially cancers of the breast and reproductive system. We also continue to assess a range of possible health effects related to DES exposure, monitoring for yet unanticipated health risks. Finally, we evaluate doing more detailed studies of specific DES-related conditions. One of the major problems in studying DES is establishing a cohort with proof of exposure. DES exposure typically occurred up to 40 or more years ago and most prenatal records have been destroyed, obstetricians have retired or are deceased, and mothers are deceased or do not recall their drug exposures from such a long time ago. Therefore, the DES Follow-up Study, which has followed the largest cohort of documented DES exposed people over time, represents the only remaining opportunity to study DES health effects on a population followed over a period of time.

DES Researchers

Scientific researchers, center coordinators and DES advocates