- What is DES?
DES (diethylstilbestrol) is a synthetic form of estrogen, a female hormone.
It was prescribed between 1938 and 1971 to help women with certain complications
of pregnancy (1). Use of DES declined following studies
in the 1950s that showed it was not effective in preventing pregnancy complications.
When given during the first 5 months of a pregnancy, DES can interfere with
the development of the reproductive system in a fetus. For this reason, although
DES and other estrogens may be prescribed for some medical problems, they
are no longer used during pregnancy.
- What health problems might DES-exposed daughters have?
In 1971, DES was linked to clear cell adenocarcinoma in a small number of
daughters of women who had used DES during pregnancy. This uncommon cancer
of the vagina or cervix is usually diagnosed between age 15 and 25 in DES-exposed
daughters (1). Some cases have been reported in women in
their thirties and forties. The risk to women older than age 40 is still unknown,
because the women first exposed to DES in utero are just reaching
their fifties, and information about their risk has not been gathered. The
overall risk of an exposed daughter to develop this type of cancer is estimated
to be approximately 1 in 1,000 (0.1 percent) (1). Although
clear cell adenocarcinoma is extremely rare, it is important that DES-exposed
daughters be aware of the risk and have regular physical examinations.
Scientists found a link between DES exposure before birth and an increased
risk of developing abnormal cells in the tissue of the cervix and vagina.
Physicians use a number of terms to describe these abnormal cells, including
dysplasia, cervical intraepithelial neoplasia, and squamous intraepithelial
lesions (1). These abnormal cells resemble cancer cells
in appearance; however, they do not invade nearby healthy tissue as cancer
cells do. Although these conditions are not cancer, they may develop into
cancer if left untreated. DES-exposed daughters should have a yearly Pap test
and pelvic exam to check for abnormal cells. DES-exposed daughters may also
have structural changes in the vagina, uterus, or cervix, as well as irregular
menstruation and an increased risk of miscarriage, ectopic (tubal) pregnancy,
infertility, and premature births (1).
Evidence from a recent study suggests that daughters of women who took DES
during pregnancy may have a slightly increased risk of breast cancer after
age 40. The risk of breast cancer for DES-exposed women over age 40 was 1.9
times the risk of breast cancer for unexposed women of the same ages. The
increased risk association was present for all breast cancer risk factors
examined, and did not differ by tumor receptor status, tumor size, or lymph
node involvement (2).
Although this evidence suggests that prenatal DES exposure increases the
risk of breast cancer, breast cancer is still a relatively rare event among
DES-exposed women. For every 1,000 DES-exposed women aged 45 to 49, 4 new
cases of breast cancer per year would be expected, compared with 2 new cases
per year in every 1,000 unexposed women (3).
While the greater risk above age 40 is statistically significant, i.e., is
more than would be expected to happen by chance alone, it is still based on
relatively small numbers. The actual risk could be quite a bit lower or higher.
Therefore, additional research is needed to be sure that the increased risk
was caused by DES (2).
- What health problems might DES-exposed sons have?
There is some evidence that DES-exposed sons may have testicular abnormalities,
such as undescended testicles or abnormally small testicles. The risk for
testicular or prostate cancer is unclear; studies of the association between
DES exposure in utero and testicular cancer have produced mixed results.
In addition, investigations of abnormalities of the urogenital system among
DES-exposed sons have not produced clear answers (1).
- What health problems might DES-exposed mothers have?
Women who used DES may have a slightly increased risk of breast cancer. Current
research indicates that the risk of breast cancer in DES-exposed mothers is
approximately 30 percent higher than the risk for women who have not been
exposed to this drug (1). This risk has been stable over
time, and does not seem to increase as the mothers become older. Additional
research is needed to clarify this issue and whether DES-exposed mothers are
at higher risk for any other types of cancer.
- How can people find out if they took DES during pregnancy or were exposed
to DES in utero?
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 (1).
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.
- What should DES-exposed daughters do?
It is important for women who believe they may have been exposed to DES before
birth to be aware of the possible health effects of DES and inform their doctor
of their exposure. It is important that the physician be familiar with possible
problems associated with DES exposure, because some problems, such as clear
cell adenocarcinoma, are likely to be found only when the doctor is looking
for them. A thorough examination may include the following:
-
Pelvic examination—A doctor performs a physical examination
of the reproductive organs. An examination of the rectum also should be
done.
-
Palpation—As part of a pelvic examination, the doctor
feels the vagina, uterus, cervix, and ovaries for any lumps. Often palpation
provides the only evidence that an abnormal growth is present.
-
Pap test—A routine cervical Pap test is not adequate for
DES-exposed daughters. The cervical Pap test must be supplemented with
a special Pap test of the vagina called a “four-quadrant”
Pap test, in which cell samples are taken from all sides of the upper
vagina.
-
Iodine staining of the cervix and vagina—An iodine solution
is used to temporarily stain the linings of the cervix and vagina to detect
adenosis (a noncancerous but abnormal growth of glandular tissue) or other
abnormal tissue.
-
Colposcopy—In colposcopy, a magnifying instrument is used
to view the vagina and cervix. Some doctors do not perform colposcopy
routinely. However, if the Pap test result is not normal, it is very important
to check for abnormal tissue.
-
Biopsy—Small samples of any tissue that appears abnormal
on colposcopy are removed and examined under a microscope to see whether
cancer cells are present.
-
Breast examinations—Researchers are continuing to study
whether DES-exposed daughters have a higher risk of breast cancer than
unexposed daughters; therefore, DES-exposed daughters should continue
to rigorously follow the routine breast cancer screening recommendations
for their age group.
- What should DES-exposed mothers do?
A woman who took DES while pregnant (or suspects she may have taken it) should
inform her doctor. She should try to learn the dosage, when the medication
was started, and how it was used. She also should inform her children who
were exposed before birth so that this information can be included in their
medical records. DES-exposed mothers should have regular breast cancer screenings
and yearly medical checkups that include a pelvic examination and a Pap test.
- What should DES-exposed sons do?
DES-exposed sons should inform their physician of their exposure and be examined
periodically. While the level of risk of developing testicular cancer is unclear
among DES-exposed sons, males with undescended testicles or unusually small
testicles have an increased risk of developing testicular cancer, whether
or not they were exposed to DES.
- Is it safe for DES-exposed daughters to use oral contraceptives or hormone
replacement therapy?
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 are unsafe for DES-exposed daughters, some doctors believe these women
should avoid these medications because they contain estrogen. Structural changes
in the vagina or cervix should cause no problems with the use of other forms
of contraception, such as diaphragms or spermicides.
- Do DES-exposed daughters have unusual problems with fertility and pregnancy?
Multiple studies have found an increased risk of premature births, miscarriage,
and ectopic pregnancy associated with DES exposure (1).
In an analysis of data published in 2000, researchers found that DES daughters
were three times more likely to have had premature births and four times more
likely to have had a miscarriage or ectopic pregnancy than unexposed daughters.
Full-term infants were delivered in the first pregnancies of 64.1 percent
of exposed women compared with 84.5 percent of unexposed women (4).
Early studies investigating a possible link between DES exposure and infertility
produced conflicting results. However, a study published in 2001 that compared
DES-exposed and unexposed daughters found that DES-exposed daughters have
a higher risk of infertility than unexposed women, and the increased risk
of infertility is mainly due to uterine or tubal problems (5).
- What is the focus of current research on DES exposure?
Researchers continue to study DES-exposed daughters as they move into the
menopausal years. The cancer risks for exposed daughters and sons are also
being studied to determine if they differ from the unexposed population. In
addition, researchers are studying possible health effects on the grandchildren
of mothers who were exposed to DES during pregnancy (also called third-generation
daughters or DES granddaughters) (6).
Two published studies have examined DES granddaughters for possible abnormalities.
A 1995 study found that the age menstruation began was not affected by the
mother’s exposure to DES (7). In a 2002 study, researchers
compared DES granddaughters’ pelvic exams to the results of their mothers’
first pelvic exams. None of the granddaughters’ pelvic exams showed
changes usually associated with DES exposure. The researchers concluded that
third-generation effects of in utero DES exposure are unlikely (6).
A recent and larger study using questionnaires to daughters of mothers who
were exposed in utero to DES (granddaughters), however, shows a slight
effect on menstrual periods—later attainment of menstrual regularization
and more irregular periods—in the exposed granddaughters compared with
the unexposed granddaughters. Also, there was a suggestion that infertility
was greater among the exposed, and the exposed tended to have fewer births.
Because a number of these associations are based on small numbers of events,
researchers will continue to study these women to further clarify these findings
(8).
Researchers are also following up on the observation that exposure to DES
may lead to an increased risk of breast cancer. A 2006 analysis found that
DES exposure in utero was associated with a slightly increased risk
of breast cancer. The experience of the women thus far suggests that increased
risk might be restricted to women age 40 or older. Further follow-up is needed
to confirm this and to characterize risk as the women age.
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 (9).
- Where can DES-exposed people get additional information?
Resources for people who were exposed to DES include the following:
| Organization: |
Centers for Disease Control and Prevention
(CDC) |
| Address: |
CDC’s DES Update
Mail Stop E–29
1600 Clifton Road, NE.
Atlanta, GA 30333 |
| Telephone: |
1–800–232–4636 (toll-free) |
| E-mail: |
cdcinfo@CDC.gov |
| Internet Web site: |
http://www.cdc.gov/des/index.html |
The CDC’s DES Update Web page provides consumers, health care providers,
and DES Update partners with up-to-date information about the health effects
of DES, and screening and treatment options for DES-exposed groups. The Interactive
DES Self-Assessment Guide is designed to help consumers determine whether
they might have been exposed to DES between 1938 and 1971. Research on the
children of DES daughters is also available on the site.
DES Action USA is a consumer group organized by individuals who were exposed
to DES. It provides information, referrals, and support for DES-exposed people
and health professionals.
| Organization: |
The Registry for Research on Hormonal
Transplacental Carcinogenesis (Clear Cell Cancer Registry) |
| Address: |
The University of Chicago
Department of Obstetrics and Gynecology
5841 South Maryland Avenue
Chicago, IL 60637 |
| Telephone: |
773–702–6671 |
| Fax number: |
773–834–2341 |
| E-mail: |
danderso@babies.bsd.uchicago.edu |
| Internet Web site: |
http://obgyn.bsd.uchicago.edu/registry.html |
The Registry for Research on Hormonal Transplacental Carcinogenesis (also
called the Clear Cell Cancer Registry) is a worldwide registry for individuals
diagnosed with clear cell adenocarcinoma of the vagina and/or cervix. Staff
members also answer questions from the public.
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