What is the Registry?
What is DES and when was it used?
What health
problems are associated with DES exposure?
What is CCA?
Who can be in the Registry?
Who can I contact to register?
Current Registry Accessions
Related Sources of Information
What is the Registry?
The Registry for Research on Hormonal Transplacental
Carcinogenesis (the Registry) is an international research registry
of cancer patients with clear cell adenocarcinoma
(CCA) of the vagina and/or cervix or other specific gynecologic cancers
who may or may not have been exposed to diethylstilbestrol
(DES) or other synthetic hormones in utero (while still in their
mother's womb). The Registry was established in 1971 at Massachusetts
General Hospital by Dr. Arthur L. Herbst and colleagues to investigate
the development of CCA of the vagina and/or cervix in young women born
since 1940.
The development of most of the vaginal tumors has
been linked to the ingestion of DES during pregnancy. Because
these tumors are rare in young women, the Registry was established to centralize
data collection on this rare carcinoma. Varying amounts of information
on the epidemiology, clinical aspects and pathology of these tumors has
been obtained.
Top of PageWhat is DES and when was it used?
DES is a synthetic form of estrogen, which is a
female hormone. It was first synthesized in 1938 and was the first
orally active estrogen. It became very popular for use during pregnancy
to prevent miscarriage. It was estrogen in pill-form that could be
taken daily in small amounts. It was believed that the extra estrogen
taken during pregnancy would help a pregnant woman have a healthy baby.
DES was used from approximately 1941 until it was banned for use in pregnancy
in 1971. The exact number of women who took DES during pregnancy
is unknown, but it has been estimated that approximately two to four million
women were treated during pregnancy with DES or other nonsteroidal synthetic
estrogens, such as dienestrol or hexestrol.
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What health problems are associated with DES exposure?
Daughters:
DES-exposed female babies may have structural changes
in the vagina, cervix, uterus and/or fallopian tubes. Sometimes these
structural changes can contribute to problems later, when the child becomes
an adult. These structural abnormalities can make it more difficult
to conceive a child or to carry a pregnancy to full term. An unfavorable
pregnancy outcome (particularly premature birth, mid-trimester miscarriage,
and tubal pregnancies) may occur in almost half of the DES-exposed daughters.
DES-exposed females also have an increased risk
of developing a rare genital tract cancer: clear cell
adenocarcinoma (CCA) of the vagina and/or cervix.
DES-exposed daughters should be aware of possible
health effects of DES exposure and inform their doctor of this exposure.
The examination of the DES-exposed female should be conducted like a normal
thorough pelvic examination. One difference is that the entire vaginal
canal should be inspected and surgical lubricants should not be used since
they can interfere with the interpretation of the Pap smear. Cells
for the Pap smear should be taken from the vagina as well as from the ectocervix
and endocervical canal.
Relevant Recent Publications (not a complete list)
Palmer JR, et al: Prenatal diethylstilbestrol exposure and risk of breast cancer. Cancer Epidemiology Biomarkers and Prevention, August 2006.
Using data collected by participants in the National Cancer Institute’s DES Follow-up Study, it was found that DES-exposed daughters do not appear to have an increased risk of breast cancer through age 40. For women aged 40 and older, prenatal DES exposure may increase the risk of breast cancer, with exposed women having about two times the risk in comparison to unexposed women. However, it is still important to remember that breast cancer is relatively rare even among DES-exposed women: for every 1,000 DES-exposed women aged 45-49, we would expect about 4 new cases of breast cancer each year, compared to 2 new cases per year in 1,000 unexposed women. These findings underscore the need for regular screening for breast tumors.
Hatch EE, et al: Age at natural menopause in women exposed to diethylstilbestrol in utero. American Journal of Epidemiology, 1 October 2006; 164:682-688.
Data regarding menopause was also collected from questionnaires filled out by participants in the National Cancer Institute’s DES Follow-up Study. It was found that “the average age at menopause was 52.2 years in unexposed women and 51.5 years in DES-exposed women.” While this study shows that DES daughters seem to be at risk for earlier menopause, the study did not established the cause. The researchers speculated that this might be related to the number of ovarian follicles produced before birth. If a DES daughter starts out with fewer follicles, she would be expected to utilize all of her follicles sooner than a woman who started with a greater number of follicles. This could lead to an earlier menopause.
Sons:
There is some concern that DES-exposed sons
may also have some reproductive abnormalities. To date, some genital
tract abnormalities have been reported, such as epididymal cysts, cryptorchidism
(undescended testis), and testicular hypoplasia (testis that are not fully
developed). Males with undescended testicles or unusually small testicles
have an increased risk of developing testicular cancer whether or not they
are exposed to DES. A physician should evaluate these situations.
Abnormalities in semen analyses have also been reported. An increased
risk in the development of malignancy in DES-exposed males has not been
demonstrated. Studies in the past have suggested possible infertility
problems in DES-exposed males but a recent follow-up study indicates that
DES exposure did not impair fertility or sexual function in adult men. This is being studied in a collaborative investigation by the National
Cancer Institute
Relevant Recent Publications (not a complete list)
Wise L, et al: Time to pregnancy and secondary sex ratio in men exposed prenatally to diethylstilbestrol. American Journal of Epidemiology, 166:765-774, October 1, 2007.
There have been conflicting research results through the years as to whether or not DES sons have higher infertility rates than unexposed males. Data was collected from participants in the National Cancer Institute’s DES Follow-up Study and results show that DES exposure does not adversely affect fertility rates for exposed males. The study found that DES-exposed males were able to father children at similar rates to those for unexposed males. There was a very slight difference in the sex ratio of the children born, with DES-exposed men fathering more girls than boys, but this difference was very small..
Mothers:
Because of the high dose of DES taken during
pregnancy by some of the exposed mothers, there has been concern of a possible
increased risk of estrogen-sensitive tumors in this group, particularly
breast cancer. Currently, an increased risk of breast cancer in DES-exposed
mothers has not been conclusively demonstrated. The current guidelines
for breast cancer screening and examination in DES-exposed mothers are
the same as for unexposed women.
Grandchildren:
Preliminary studies thus far have not shown
any “third” generation effects of exposure to DES.
Top of PageWhat is CCA?
Clear cell adenocarcinoma (CCA) of the vagina and/or
cervix is a very rare type of cancer, so named because of the way the cells
look under a microscope. The Registry specifically studies CCA of
the vagina and cervix in young women born after 1948. The age range
of females with this type of cancer who have been reported to the Registry
is from 7 to 48 years of age. Previously this cancer had been found
only rarely and then primarily in women over 50. The upper age limit
for developing CCA is unknown.
Top of PageCurrent Registry Accessions
The Registry, as of December 2007, has accessioned approximately
760 cases of clear cell adenocarcinoma (CCA), 2/3 of which are associated
with prenatal diethylstilbestrol (DES) exposure. The initial age-incidence
curve showed a peak between ages 15-25 years among the DES-exposed.
Currently cases up to age 55 have been accessioned and there is a suggestion
of a possible increase in frequency among DES-exposed beginning to appear
in those over 40 years of age. Cases of primary adenocarcinoma of
the endometrium in patients under age 40 have been reported to the Registry,
as well as isolated cases of primary mucinous adenocarcinoma of the vagina
in the DES-exposed. These sporadic occurrences are currently under
investigation.
Therefore, we accession the following cases:
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Who can be in the Registry?
Who can I contact to register?
Top of PageRelated Sources of Information:
National Cancer Institute:
Regarding DES: Questions
and Answers
Regarding Cancer
Research
The DES Cancer Network is an non-profit support organization made up of women who have had CCA and are exposed to DES.
DES Action USA is a national,
non-profit consumer organization dedicated to informing the public about
DES and helping DES-exposed individuals (mothers, daughters and sons exposed
to DES).
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Please note: We are not able to answer on-line medical inquiries.
Last Updated: 16 January 2008.
Send questions and comments about this page to:
danderso1@babies.bsd.uchicago.edu