Clinical Implications of DES

ANCC Contact Hours 1.0

Kelly Kruse MS, RN-C, WHNP Diane Lauver PhD, RN, CS, FAAN Karen Hanson MS, RN-C, WHNP

iethylstilbestrol (DES), a syn- pregnancy healthier.”1 Peak use occurred thetic nonsteroidal estrogen, between the late 1940s and early 1950s. D was used for over 3 decades un- In the years between 1938 and 1971, der the mistaken assumption that it the advice of a medical professional was would prevent miscarriages and lead to rarely questioned. Patients believed that a healthy pregnancy. DES has not been the physician knew best, and the concept in widespread use since 1971 when the of informed consent was unknown at the Food and Drug Administration (FDA) time. It was widely believed that DES issued a warning against prescribing it would make a pregnancy healthier. Many to pregnancy women. However, an esti- women were unaware they were taking mated 5-10 million people in the U.S. DES because the drug was marketed in have been exposed and are at increased combination with vitamins. In fact, DES risk for several health problems. Once prescribed to pregnant women to and similar DES-type drugs were mar- Although DES has not been ap- keted under dozens of brand names (see prevent risk of spontaneous abortion, proved for use in pregnant women since Table: “Names of DES and DES-Type 1971, the long-term effects of the drug diethylstilbestrol (DES) is now associ- Drugs”), and manufactured by over 200 2 continue. DES is clearly documented as ated with an increased risk of breast U.S. drug companies at different times. a cause of clear cell adenocarcinoma Randomized trials of the drug were (CCA) of the vagina and cervix in women cancer, clear cell adenocarcinoma not conducted until the early 1950s, and exposed prenatally (DES daughters),and (CCA) of the vagina and cervix, and re- the results failed to show a clear benefit is associated with a modest increase in for pregnancy outcome from the use of productive anomalies. This article will risk of breast cancer in women who were DES.3 Although this research did not stop prescribed the drug during pregnancy. summarize the potential long-term the use of DES for pregnant women, the In addition, it has been linked to repro- number of DES prescriptions after 1953 health implications of DES, the role of ductive anomalies in both women and gradually declined. By the late 1960s, the men (DES sons) exposed in utero. Un- nurse practitioners in identifying ex- Boston Lying-In Hospital (where DES fortunately, many health care providers posed individuals, and proper clinical use began) was treating less than 1% of are unaware of the health implications pregnancies with the drug.1 for those exposed to the drug. management. Finally, in 1971, the FDA contraindi- cated the use of DES in pregnant women. ■ Background and Epidemiology Prenatal exposure to DES had been undeniably linked to CCA In the United States, DES was prescribed to pregnant women of the vagina in very young women (late teens or early twen- primarily to prevent the risk of spontaneous abortion from ties).4 Before DES was prescribed, this cancer was rarely seen 1938, when it was first synthesized, to 1971. The drug was in women under age 50. prescribed liberally to women who had a history of miscar- Research on the potential health outcomes of exposure riage or diabetes, or sometimes simply “to make a healthy of women who took the drug while pregnant, as well as their

26 The Nurse Practitioner • Vol. 28, No. 7 www.tnpj.com Clinical Implications of DES

children,has now shown possible lifelong In the years between 1938 Exposure During Pregnancy effects. Current studies continue to look Women who took DES while pregnant and 1971, the advice of a at these effects and at the possibility of are at a modestly increased risk for de- third-generation effects. Although the medical professional was veloping breast cancer (RR=1.3). There majority of the medical community has rarely questioned. It was widely believed is no evidence that these women are at written off DES exposure as a health con- increased risk for other hormone-related cern,women and men who may have that DES would make a pregnancy health- female cancers. Also, the risk of breast been exposed to DES in utero are as ier. Many women were unaware they cancer in DES-exposed women does not young as their late 30s today. Because ex- appear to be compounded by the use of were taking DES because the drug was posure to DES is still a current health hormone replacement therapy (HRT).5 concern, the Centers for Disease Control marketed in combination with vitamins. and Prevention (CDC) and the National DES Daughters Randomized trials of the drug were not Cancer Institute (NCI) initiated a na- Women exposed to DES in utero have the tionwide education program to increase conducted until the early 1950s, and the most documented negative health effects. health care providers’ awareness of the results failed to show a clear benefit for These women are at risk for structural far-reaching effects of DES exposure. anomalies of the reproductive tract, Nurse practitioners (NPs) are in key po- pregnancy outcome from the use of DES. pregnancy complications, and CCA of sitions to assess for history of exposure the vagina and cervix.6 The risk for CCA and to provide care that is sensitive to individual risks. is small, yet significant at 1:1000. In DES daughters whose mothers either took DES before the 9th week of pregnancy ■ Review of DES Exposure and Current Health Risks or had at least one spontaneous abortion, this risk may be Target populations for exposure include women who were doubled.7 Neither the use of oral contraceptives nor preg- given DES during pregnancy,and their daughters (DES daugh- nancy is associated with an increased risk of CCA in either ters) and sons (DES sons) exposed in utero. nonexposed or DES-exposed women.7 The peak age-incidence for CCA in DES daughters is 17- 23 years, but there is no known upper age limit for its devel- Names of DES and DES-type Drugs opment,8 and a second age incidence of CCA is a concern as 8,9 Benzestrol Fonatol Palestrol DES daughters enter menopause. Chlorotrianisene Gynben Restrol DES daughters often have higher incidences of infertil- Comestrol Gyneben Stilbal ity and pregnancy complications than their unexposed coun- Cyren A H-Bestrol Stilbestrol terparts. These include ectopic pregnancies, miscarriage, Cyren B Hexestrol Stilbestronate preterm labor and preterm births.6,10,11 Structural and histo- Delvinal Hexoestrol Stilbetin logical anomalies of the reproductive tract are also more com- DES Menocrin Stilbinol mon in DES daughters. These include a T-shaped uterus and DesPlex Meprane Stilboestroform Dibestil Mestilbol Stilboestrol malformations of the cervix, vaginal adenosis, cervical in- 10,6 Dienestrol Methallenestril Stilestrate traepithelial neoplasia, leukoplakia, and mosaicism. These Dienoestrol Microest Stilooestrol DP changes likely contribute to the higher incidence of preg- Diestryl Mikarol Stilpalmitate nancy-related problems in exposed women. Diethylstilbenediol Mikarol forti Stilphostrol While little is known about DES granddaughters, one Diethylstilbestrol Milestrol Stil-Rol study showed that female offspring of DES daughters have Dipalmitate Monomestrol Stilronate not experienced the types of genital abnormalities associated Diphosphate Neo-Oestranol I Stilrone 12 Dipropionate Neo-Oestranol II Stils with in utero DES-exposure. In these women, the age of 13 Digestil Nulabort Synestrin menarche is unaffected by the mother’s DES exposure. Domestrol Oestrogenine Synestrol Estilben Oestromenin Synthoestrin DES Sons Estrobene Oestromon Vallestril DES sons have a three-fold increase in reproductive abnor- Estrobene DP Orestol Willestrol malities.14 They are at significantly higher risk for epididymal Estrosyn Pabestrol D cysts, undescended and hypoplastic testes, and varicoceles,16 Note: The FDA currently controls the manufacture and distribution of DES, but researchers have not found a decrease in fertility or sex- which is used only for veterinary and human clinical trial purposes. U.S. ual function.14 In a recent study, the incidence of testicular chemical producers manufacture the substance. cancer was slightly higher in DES sons than in nonexposed

www.tnpj.com The Nurse Practitioner • July 2003 27 Clinical Implications of DES

Vaginal, Cervical and Uterine Abnormalities in DES-exposed Women

Normal Cervix Mosaic Pattern Cervical Cockscomb, collar and pseudopolyp of the cervix

Vaginal Adenosis Clear Cell Carcinoma

men, however the increase was not statistically significant. tion based on current research. No single set of guidelines is Whether such exposure is associated with testicular cancer appropriate for everyone exposed to DES. The suggestions in risk is still unclear,16 however, DES sons are now approaching this article assist the NP working with DES-exposed patients the age at which the incidence of many cancers increase. to help them make individual and fully-informed health care It is well established that cancer is more likely to develop decisions. in hypoplastic and undescended testicles, whether or not the The first and most difficult task is to determine whether man has been DES exposed. With their higher prevalence of the patient was exposed to DES. Obstetrical or pharmaceuti- these congenital anomalies, DES sons may be secondarily at cal records provide the best evidence of exposure, but as time higher risk for testicular cancer.16 In addition, animal stud- passes, such evidence frequently cannot be obtained. A sug- ies17 and biologic plausibility raise concerns of the possible gestive medical history (prior miscarriage in women who were increased risk of two kinds of rare cancer found in middle- prescribed DES during pregnancy) and/or clinical signs (re- aged and older men. These are cancers of the rete testes and productive tract anomalies, ectopic pregnancy, repeated mis- of the prostatic utricle, a vestigial structure at the top of the carriage in DES daughters) may be the only clues to prenatal prostate that extends into the urethra.As with the vagina, both DES exposure. Assessment of known DES exposure, either by these structures are embryonically derived from the müller- ingestion or in utero, should be routine in the health history. ian duct and as a result, may also be targeted by DES in early This is especially important in women who were pregnant gestation.15 between 1940 and 1971, and in women and men born dur- Little is known about third generation males (sons of DES ing those years. In addition, women who develop breast can- daughters), however, one study found an increased incidence cer without family history or other risk factors should be of hypospadias among third generation males.19 These third assessed for exposure. Women with pregnancy-related com- generation effects are just beginning to be studied. plications and/or reproductive tract cellular and structural changes, and men with reproductive abnormalities should ■ Clinical Implications also investigate the possibility of in utero exposure to DES. The NP’s goal is to help DES-exposed patients identify their Knowledge of DES exposure will not change the treatment risk for related health problems and to provide client educa- or outcome of many related health care problems, but it can

28 The Nurse Practitioner • Vol. 28, No. 7 www.tnpj.com Clinical Implications of DES

provide an explanation that may help the Women exposed to DES in tampons, which may also be character- individual deal with the health problem. istic of exposure.19 Uterine abnormali- utero have the most doc- In addition,that person can educate other ties should be considered in women with exposed family members to initiate rou- umented negative health these vaginal findings, specifically a T- tine health screening. effects. These women are at risk for shaped uterus. Obvious or suspected findings on bimanual exam may be fol- Exposed While Pregnant structural anomalies of the reproduc- lowed up with ultrasound or biopsy. This Women who were pregnant between tive tract, pregnancy complications, thorough and careful approach to the gy- 1940 and 1971 with a history of miscar- necologic exam should be used through- and CCA of the vagina and cervix. The riage and preterm labor should be as- out a woman’s life, since CCA is now sessed for possible exposure to DES. peak age-incidence for CCA in DES being diagnosed at later ages, often be- Asking about the use of DES or other ginning in the 30s and 40s.8 daughters is 17-23 years, but there is no medications during pregnancy is impor- Laboratory cytology includes a Pap tant because DES was marketed under known upper age limit for its develop- smear of the upper vagina, and the mid- many names and a woman may not know ment, and a second age incidence of dle and lower third if epithelial changes that she was exposed. are evident, and sampling from the en- Because of the potential increased CCA is a concern as DES daughters en- docervix and ectocervix. The ThinPrep risk of breast cancer in women who were ter menopause. DES daughters often have Pap test is recommended, and DES ex- prescribed DES, the importance of a posure should be noted for cytology. Any higher incidences of infertility and preg- yearly breast exam should be emphasized. woman with abnormal cytology or who Mammograms may be recommended ac- nancy complications than their unex- has a nodule or lesion should be referred cording to current guidelines and based for colposcopy with biopsy when indi- posed counterparts. These include ec- on risk factors. A thorough breast self- cated. Women with adenosis or cervical exam compliments professional screen- topic pregnancies, miscarriage, preterm anomaly with no abnormal cytology, ings. labor and preterm births. nodule, or lesion may continue with an- Women who were prescribed DES nual screening as described above. should also be reassured that there is no Women with a normal pelvic exam and evidence of an increased risk for other hormone-related cytology may also continue with the described annual gyne- female cancers. When counseling regarding the menopausal cologic exam.6 Endometrial biopsy should be performed with use of hormones, NPs can reassure women that the risk of caution in DES-exposed women due to the possible shorter breast cancer in DES-exposed women is not compounded distance between the cervix and fundus.10 with the use of HRT. Increased risk of infertility, ectopic pregnancies, miscarriage, preterm labor, and preterm births should be discussed. DES Daughters Symptoms of CCA should be reviewed and women reassured Some women may already be aware of in utero exposure to that neither oral contraceptive use nor pregnancy increases DES. However, if exposure status is unknown, specifically ask risk for CCA. if the patient’s mother had a history of miscarriage or preterm In regard to other methods of contraception,women with labor, or if she was prescribed a drug during pregnancy. Ob- a T-shaped uterus should be informed that this is a con- taining the mother’s health records during pregnancy is the traindication to use of the intrauterine device. Women with best way to confirm exposure. cervical malformation may have problems with barrier meth- In women with suspected or known DES exposure, NPs ods (the cervical cap and diaphragm may not fit properly, should rule out symptoms of CCA. A history of abnormal thus reducing effectiveness). In addition, women with cervi- vaginal bleeding or discharge may be symptomatic of CCA.4,8 cal malformations should be informed that these changes are Lifelong yearly breast and pelvic exams are recommended. likely to contribute to a higher incidence of pregnancy- The pelvic exam should include vulvar inspection, along with related problems. a speculum exam with visual inspection of the vagina and Fertility awareness education, specifically the sympto-ther- cervix for mosaicism, vaginal adenosis, leukoplakia and/or mal method, may be helpful for women planning a pregnancy. cervical anomalies common as a result of DES exposure. Pal- Due to the increased risk of ectopic pregnancy,a woman should pation of the vaginal walls is important because CCA has been be informed of these symptoms and instructed to call for preg- known to present as a subepithelial lump.6 Women with vagi- nancy confirmation as soon as she has missed a period. Trans- nal inelasticity often report dyspareunia and difficulty using vaginal ultrasound at 6 weeks last menstrual period is usually

www.tnpj.com The Nurse Practitioner • July 2003 31 Clinical Implications of DES

recommended to confirm intrauterine DES sons have a three-fold PSA test, but rather by blood in the urine, pregnancy and early prenatal care is im- it is recommended that DES sonsre- increase in reproductive portant.6 Inform the patient that she gardless of agehave a urinalysis for oc- can expect more frequent monitoring abnormalities. They are at cult blood in the urine as part of routine 15 throughout her pregnancy to reassure her. significantly higher risk for epididymal yearly or bi-yearly examinations. Other periodic cancer screening should occur DES Sons cysts, undescended and hypoplastic regardless of DES exposure. Male children exposed to DES should fol- testes, and varicoceles, but researchers Education regarding testicular self- low routine periodic health screening re- exam (TSE) should be provided, and a have not found a decrease in fertility or gardless of age. Men who present with monthly TSE is recommended. Men with genital anomalies (including epididymal sexual function. Obstetrical or pharma- undescended and hypoplastic testicles cysts, undescended and hypoplastic should be informed of a possible increased ceutical records provide the best evi- testes,and varicoceles) should be assessed risk of testicular cancer regardless of for a history of exposure in utero. Clini- dence of exposure, but as time passes, known DES exposure. DES-exposed men cal testicular exam is recommended on a such evidence frequently cannot be ob- with or without the presence of genital yearly and bi-yearly basis with specific anomalies should be reassured that there assessment for a testicular lump or nod- tained. A suggestive medical history is no known decrease in fertility or sexual ule.15 While testicular cancer in general (prior miscarriage in women who were function.14 Men should be informed that is considered a disease of young men (late to date, there is no indication that in utero prescribed DES during pregnancy) and/or teens to early 30s), rete testis cancer in exposure to DES influences the develop- particular occurs in men past age 50. clinical signs (reproductive tract anom- ment of cancer overall. These men should Prostate and prostatic utricle cancer oc- be encouraged, however, to participate in alies, ectopic pregnancy, repeated mis- curs in middle-aged and older men, and regular screening for other types of can- regular, periodic prostate exams should carriage in DES daughters) may be the cer, as most DES-exposed men are now be included in the physical exam for these only clues to prenatal DES exposure. approaching the age at which most can- patients. cers are detected. DES-exposed men who are middle aged or older should have periodic prostate-specific antigen (PSA) tests. Because Third Generation Effects cancer of the prostatic utricle is unlikely to be detected by a Although animal studies have shown some increased incidence of anomalies typical of DES exposure in unexposed rodents whose parents DES Education Resources were exposed to DES in utero, studies of third generation effects in humans are DES Action USA National Cancer Institute 610 16th Street Cancer Information Service just beginning. In the few studies that do Oakland, CA 94612 M-F 9:00 am to 7:00 pm exist, age of menarche in DES grand- [email protected] (800) 4-CANCER or (800) 422-6237 daughters is unaffected by the mother’s http://www.desaction.org TTY: (800) 332-8615 prenatal DES exposure,12 and of these www.cancer.gov DES Cancer Network women, genital abnormalities associated 514 10th St., NW, Suite 400 *Registry for Research on Hormonal with in utero DES exposure have not been Washington, DC 20004-1403 Tr ansplacental Carcinogenesis found.13 In third generation males (sons (800) DES-NET4 or (202) 628-6330 University of Chicago – [email protected] Dept. of Obstetrics & Gynecology of DES daughters), increased hypospa- 5841 S. Maryland Ave. MC 2050 dias have been found, although long- DES Sons Network Chicago, IL 60637 term health implications of this are 10 Sleepy Hollow Place http://obgyn.bsd.uchicago.edu/registry.html uncertain.19 Cherry Hill, NJ 08003 *This is an international research registry of cancer pa- (609) 795-1658 tients who may or may not have been exposed to DES or other synthetic hormones in utero. Eligible candidates for ■ In Conclusion American Cancer Society the registry include women who were born during or af- NPs are in key positions to identify DES 1599 Clifton Road ter 1948 and have been diagnosed with clear cell adenocarcinoma of the vagina and/or cervix, regardless of DES exposure in patients. In addition to clin- Atlanta, GA 30329 exposure. Women who have been exposed to DES and (800) ACS-2345 have mucinous carcinoma of the vagina, primary en- ical assessment, NPs can use their health www.cancer.org dometrial carcinoma, and/or carcinoma of the fallopian education and counseling skills to help tube are also candidates. individuals understand the health impli-

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Clinical Implications of DES

DES Up Close By Fran Rosen, MA, RN

When I discovered that I was a DES daughter, I became cinoma (1:1000). Clear cell adenocarcinoma most com- an informed health care consumer and advocate. Here are monly affects young women (age 15 through the early some facts that every practitioner should know about the 20s), but has been found in DES daughters between the prevalence of DES exposure and the significance it holds ages of 7 and 42. for your patients. ■ Helping Your Patient Learn DES Status ■ The Pelvic Exam for a DES Daughter Patients born between 1941 and 1971 may be unsure if The recommended pelvic exam for a DES daughter is dif- they are DES-exposed. You can assess whether there is ev- ferent from a routine exam. In the routine exam, the Pap idence of any change in your patient’s reproductive tract. smear is taken only from the cervix, but in a DES exam, a As this cohort ages, it becomes more difficult to ob- separate Pap smear is taken from the surfaces of the up- tain information. If your patient is unable to ask her per vagina as well. mother, she may want to ask her relatives about her It is recommended that DES daughters have a gyne- mother’s history of pregnancy. If she was prescribed any cological exam once a year (beginning at puberty) con- medication to prevent miscarriage or improve the preg- sisting of: nancy, this may indicate DES exposure. It may be impos- • A thorough pelvic examination, with a visual exami- sible to access old medical records. Some hospitals keep nation of the vagina and cervix for particular abnor- records for 30 years or more, while others do not. In ad- malities; dition, medical records are legal documents protected by • A cervical Pap test; privacy laws. Your patient may find that only her mother • A vaginal Pap test taken from all four quadrants of the can obtain these records. vagina; • Palpation of the walls of the vagina, uterus, cervix, and ■ What About Legal Action? ovaries to check for lumps. While there has never been a class-action lawsuit, many • The initial DES examination should include iodine DES-exposed patients (mostly daughters) have individu- staining of the cervix and vagina to check for abnor- ally sued the drug companies that manufactured DES and mal tissues or noncancerous abnormal growths of glan- have obtained compensation. A patient’s ability to sue de- dular tissue. pends on many factors. You can refer your patient to DES • A colposcopy may be necessary when there is change Action. in the vaginal or cervical tissue, or an abnormal pap smear. ■ Stay Informed This year, the Centers for Disease Control and Prevention ■ DES Daughters At a Glance (CDC), using funds from the United States Congress, DES daughters have an increased risk of infertility, ec- launched the DES Update Web site. In addition to pro- topic pregnancy, miscarriage, menstrual irregularities, viding resources to individuals who were pregnant or born preterm labor, and increased incidence of abnormal pap during 1938–1971, health care providers can access edu- smears and cervical carcinoma in situ. cational materials such as DES case studies, presentations, Twenty-five to 40 percent of DES daughters experi- and self study materials by visiting www.cdc.gov/DES/. ence structural abnormalities of the uterus, cervix, or up- RESOURCES: per vagina. This includes a T-shaped or small uterus, or http://www.descancer.org/care.html http://www.injuryboard.com/view.cfm/ID=678 developing a growth on the cervix known as a “cervical http://www.aaronlevinelaw.com/des2.htm hood.” http://www.desaction.org/desfaq.html DES daughters have a higher-than-average risk of de- http://www.cdc.gov/DES/ Fran Rosen is Continuing Education Manager for The Nurse Practitioner at veloping a rare cancer called vaginal clear cell adenocar- Wolters Kluwer Health, Ny, Ny.

34 The Nurse Practitioner • Vol. 28, No. 7 www.tnpj.com Clinical Implications of DES

cations of DES exposure. NPs are also in a prime position to diethylstilbestrol in utero. JAMA 1998;280(7):630-4. 9. Herbst AL: Behavior of estrogen-associated female genital tract cancer and its assess whether DES exposure is creating worries, and to help relation to neoplasia following intrauterine exposure to diethylstilbestrol patients identify strategies for care and to assess their effec- (DES). Gynecologic Oncology 2000;76:147-56. tiveness. In addition to offering support, clinicians can con- 10. Goldberg JM, Falcone T: Effect of diethylstilbestrol on reproductive function. Fertil Steril 1999;72(1):1-7. tinue to review the literature for studies that may provide 11. Kaufman RH, Adam E, Hatch EE., et al: Continued follow-up of pregnancy answers and clinical recommendations for DES-exposed pa- outcomes in diethylstilbestrol-exposed offspring. Obstet Gynecol tients. 2000;96(4):483-89. 12. Kaufman RH, Adam E: Findings in female offspring of women exposed in utero to diethylstilbestrol. Obstet Gynecol 2002;99:197-200. ACKNOWLEDGEMENTS 13. Wilcox AJ, Umbach DM, Hornsby PP, et al: Gynecology: Age of menarche This summary article was supported by the Department of Health and Human amonge diethylstilbestrol granddaughters. Am J Obstet Gynecol Services, Centers for Disease Control and Prevention, the Office of Women’s Health 1995;173(3):835-836. (Washington, DC), (Order No. 00T00225101D) and the University of Wisconsin 14. Wilcox AJ, Baird DD, Weinberg CR, et al: Fertility in men exposed prenatally Center for Women’s Health and Women’s Health Research. to diethylstilbestrol. N Engl J Med 1995;332:1411-16. 15. Laitman CJ, Jonler M, Messing EM: The effects on men of prenatal exposure REFERENCES to diethylstilbestrol. In: Lipshultz LI, Howards SS, eds. Infertility in the Male, 3rd edition. St. Louis, MO: Mosby, 1997;268-79. 1. Orenberg CL: DES: The complete story. New York City: St. Martin’s Press, 16. Strohsnitter WC, Noller KL, Hoover RN, et al: Cancer risk in men exposed in 1981. utero to diethylstilbestrol. J Natl Cancer Inst 2001;93(7):545-51. 2. NCI: Exposure in utero to diethylstilbestrol and related synthetic hormones. 17. Newbold RR, Hanson RB, Jefferson WN, et al: Proliferative lesions and repro- JAMA (Sept.6, 1976)-Vol.236, No. 10, pp.1107-0019. ductive tract tumors in male descendants of mice exposed developmentally to 3. Dieckmann WJ, Davis ME, Rynkiewicz LM, et al: Does the administration of diethylstilbestrol. Carcinogenesis 2000;21(77):1355-63. diethylstilbestrol during pregnancy have therapeutic value? Am J Obstet Gy- 18. Klip H, Verloop J, Van Gool JD, et al: Hypospadias in sons of women exposed necol 1953;66:1062-75. to diethystilbestrol in utero: a cohort study. Lancet 2002;359:1102-1107. 4. Herbst AL, Ulfeler H, Poskanzen, DC: Adneocarcinoma of the vagina: associ- 19. Stillman RJ: In utero exposure to diethylstilbestrol: Adverse effects on the re- ation of maternal stilbestrol therapy with tumor appearance in young women. productive tract and reproductive performance in male and female offspring. N Engl J Med 1971:2844:878-881. Am J Obstet Gynecol 1982;142(7):905-21. 5. Titus-Ernstoff L, Hatch EE, Hoover RN, et al: Long-term cancer risk in women given diethylstilbestrol (DES) during pregnancy. Br J Cancer 2001;84(1):126-33. 6. Kaufman RH, et al. (Eds.) Identification and management of DES exposed ABOUT THE AUTHORS individuals. Bethesda, MD: National Cancer Institute, 1995. Kelly Kruse is a clinical associate professor at the University of Wisconsin-Madi- 7. Palmer JR, Anderson D, Helmrich SP, et al: Risk factors for diethylstilbestrol- son. Diane Lauver is a professor at the University of Wisconsin-Madison. Karen associated clear cell adenocarcinoma. Obstet Gynecol 2000;95(6):814-20. Hanson is a Women’s Health NP at WomanCare, Palatine, Ill. 8. Hatch EE, Palmer JR, Titus-Ernstoff L, et al: Cancer risk in women exposed to

CE Test Clinical Implications of DES

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