1. 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.

2. 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).

3. 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).

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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).

11. 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).

12. 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.

Organization:	DES Action USA
Address:	158 South Stanwood Road Columbus, OH 43209
Telephone:	1–800–DES–9288 (1–800–337–9288)
E-mail:	desaction@columbus.rr.com
Internet Web site:	http://www.desaction.org

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.

Selected References

1. National Cancer Institute. DES Research Update 1999: Current Knowledge, Future Directions. National Cancer Institute, 1999.
   
   
2. Palmer JR, Wise LA, Hatch EE, et al. Prenatal diethylstilbestrol exposure and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 2006; 15(8):1509–1514.
   
   
3. Ries LAG, Eisner MP, and Kosary CL, et al. (eds). SEER Cancer Statistics Review, 1975-2002. Bethesda, MD: National Cancer Institute, 2005. Retrieved November 3, 2006, from http://seer.cancer.gov/csr/1975_2002/.
   
   
4. Kaufman RH, Adam E, Hatch EE, et al. Continued follow-up of pregnancy outcomes in diethylstilbestrol-exposed offspring. Obstetrics and Gynecology 2000; 96(4):483–489.
   
   
5. Palmer JR, Hatch EE, Rao RS, et al. Infertility among women exposed prenatally to diethylstilbestrol. American Journal of Epidemiology 2001; 154(4):316–321.
   
   
6. Kaufman RH, Adam E. Findings in female offspring of women exposed in utero to diethylstilbestrol. Obstetrics and Gynecology 2002; 99(2):197–200.
   
   
7. Wilcox AJ, Umbach DM, Hornsby PP, Herbst AL. Age at menarche among diethylstilbestrol granddaughters. American Journal of Obstetrics and Gynecology 1995; 173(3 Pt 1):835–836.
   
   
8. Titus-Ernstoff L, Troisi R, Hatch EE, et al. Menstrual and reproductive characteristics of women whose mothers were exposed in utero to diethylstilbestrol (DES). International Journal of Epidemiology 2006; 35(4):862–868.
   
   
9. Titus-Ernstoff L, Perez K, Hatch EE, et al. Psychosexual characteristics of men and women exposed prenatally to diethylstilbestrol. Epidemiology 2003; 14(2):155–160.
   
   

# # #

Related Resources

• What You Need To Know About™ Breast Cancer ¹
• What You Need To Know About™ Cancer of the Cervix ²

National Cancer Institute (NCI) Resources

Cancer Information Service (toll-free)

Telephone: 1–800–4–CANCER (1–800–422–6237)

TTY: 1–800–332–8615

Online

NCI’s Web site: http://www.cancer.gov
LiveHelp, NCI’s live online assistance:
https://cissecure.nci.nih.gov/livehelp/welcome.asp

Glossary Terms

Not normal. An abnormal lesion or growth may be cancer, premalignant (likely to become cancer), or benign (not cancer).

A process in which anything complex is separated into simple or less complex parts.

The removal of cells or tissues for examination by a pathologist. The pathologist may study the tissue under a microscope or perform other tests on the cells or tissue. There are many different types of biopsy procedures. The most common types include: (1) incisional biopsy, in which only a sample of tissue is removed; (2) excisional biopsy, in which an entire lump or suspicious area is removed; and (3) needle biopsy, in which a sample of tissue or fluid is removed with a needle. When a wide needle is used, the procedure is called a core biopsy. When a thin needle is used, the procedure is called a fine-needle aspiration biopsy.

Cancer that forms in tissues of the breast, usually the ducts (tubes that carry milk to the nipple) and lobules (glands that make milk). It occurs in both men and women, although male breast cancer is rare.

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck. Cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the “neck”) of the uterus.

Growth of abnormal cells on the surface of the cervix. Numbers from 1 to 3 may be used to describe how abnormal the cells are and how much of the cervical tissue is involved. Also called CIN.

The lower, narrow end of the uterus that forms a canal between the uterus and vagina.

A rare type of tumor, usually of the female genital tract, in which the insides of the cells look clear when viewed under a microscope. Also called clear cell carcinoma and mesonephroma.

Examination of the vagina and cervix using a lighted magnifying instrument called a colposcope.

A synthetic form of the hormone estrogen that was prescribed to pregnant women between about 1940 and 1971 because it was thought to prevent miscarriages. DES may increase the risk of uterine, ovarian, or breast cancer in women who took it. It also has been linked to an increased risk of clear cell carcinoma of the vagina or cervix in daughters exposed to DES before birth. Also called diethylstilbestrol.

The process of identifying a disease, such as cancer, from its signs and symptoms.

A synthetic form of the hormone estrogen that was prescribed to pregnant women between about 1940 and 1971 because it was thought to prevent miscarriages. Diethylstilbestrol may increase the risk of uterine, ovarian, or breast cancer in women who took it. It also has been linked to an increased risk of clear cell carcinoma of the vagina or cervix in daughters exposed to diethylstilbestrol before birth. Also called DES.

The amount of medicine taken, or radiation given, at one time.

Any substance, other than food, that is used to prevent, diagnose, treat or relieve symptoms of a disease or abnormal condition. Also refers to a substance that alters mood or body function, or that can be habit-forming or addictive, especially a narcotic.

Cells that look abnormal under a microscope but are not cancer.

A type of hormone made by the body that helps develop and maintain female sex characteristics and the growth of long bones. Estrogens can also be made in the laboratory. They may be used as a type of birth control and to treat symptoms of menopause, menstrual disorders, osteoporosis, and other conditions.

The developing offspring from 7 to 8 weeks after conception until birth.

An organ that makes one or more substances, such as hormones, digestive juices, sweat, tears, saliva, or milk. Endocrine glands release the substances directly into the bloodstream. Exocrine glands release the substances into a duct or opening to the inside or outside of the body.

One of many chemicals made by glands in the body. Hormones circulate in the bloodstream and control the actions of certain cells or organs. Some hormones can also be made in the laboratory.

A tentative proposal made to explain certain observations or facts that requires further investigation to be verified.

The inability to produce children.

An element that is necessary for the body to make thyroid hormone. It is found in shellfish and iodized salt.

The time of life when a woman’s ovaries stop producing hormones and menstrual periods stop. Natural menopause usually occurs around age 50. A woman is said to be in menopause when she hasn’t had a period for 12 months in a row. Symptoms of menopause include hot flashes, mood swings, night sweats, vaginal dryness, trouble concentrating, and infertility.

The monthly cycle of hormonal changes from the beginning of one menstrual period to the beginning of the next.

Periodic discharge of blood and tissue from the uterus. From puberty until menopause, menstruation occurs about every 28 days when a woman is not pregnant.

By or having to do with the mouth.

One of a pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus.

Examination by pressing on the surface of the body to feel the organs or tissues underneath.

A procedure in which cells are scraped from the cervix for examination under a microscope. It is used to detect cancer and changes that may lead to cancer. A Pap test can also show conditions, such as infection or inflammation, that are not cancer. Also called Pap smear and Papanicolaou test.

Having to do with the pelvis (the lower part of the abdomen located between the hip bones).

An exam of the body to check for general signs of disease.

Medical doctor.

A doctor's order for medicine or another intervention.

Cancer that forms in tissues of the prostate (a gland in the male reproductive system found below the bladder and in front of the rectum). Prostate cancer usually occurs in older men.

A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell.

The last several inches of the large intestine closest to the anus.

The organs involved in producing offspring. In women, this system includes the ovaries, the fallopian tubes, the uterus, the cervix, and the vagina. In men, it includes the prostate, the testes, and the penis.

Something that increases the chance of developing a disease. Some examples of risk factors for cancer are age, a family history of certain cancers, use of tobacco products, being exposed to radiation or certain chemicals, infection with certain viruses or bacteria, and certain genetic changes.

Checking for disease when there are no symptoms. Since screening may find diseases at an early stage, there may be a better chance of curing the disease. Examples of cancer screening tests are the mammogram (breast), colonoscopy (colon), Pap smear (cervix), and PSA blood level and digital rectal exam (prostate). Screening can also include checking for a person’s risk of developing an inherited disease by doing a genetic test.

Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. Also called significant.

One of two egg-shaped glands inside the scrotum that produce sperm and male hormones. Also called testis.

A group or layer of cells that work together to perform a specific function.

An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancer), or malignant (cancer). Also called neoplasm.

A condition in which one or both testicles fail to move from the abdomen, where they develop before birth, into the scrotum. Undescended testicles may increase the risk for development of testicular cancer. Also called cryptorchidism.

The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called womb.

The muscular canal extending from the uterus to the exterior of the body. Also called birth canal.