Diethylstilbestrol revisited: A review of the long-term health effects

Annals of Internal Medicine

Volumn 122, Issue 10, 1995, Pages 778-788

  Giusti, Ruthann M ^a   Iwamoto, Kumiko ^a   Hatch, Elizabeth E ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DIETHYLSTILBESTROL;

CARCINOGENESIS; GYNECOLOGIC DISEASE; HUMAN; PREGNANCY; PREGNANCY DISORDER; PRIORITY JOURNAL; REVIEW;

EID: 0029053049     PISSN: 00034819     EISSN: None     Source Type: Journal    
DOI: 10.7326/0003-4819-122-10-199505150-00008     Document Type: Review

References (113)

1. Colburn T, vom Saal FS, Soto AM. Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environ Health Perspect. 1993;101:378-4.
2. Davis DL, Bradlow HL, Wolff M, Woodruff T, Hoel DG, Anton-Culver H. Medical hypothesis: xenoestrogens as preventable causes of breast cancer. Environ Health Perspect. 1993;101:372-7.
3. Sharpe RM, Skakkebaek NE. Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract? Lancet. 1993;341:1392-5.
4. DDT and associated compounds. IARC Monogr Eval Carcinog Risks Hum. 1991;53:179-249.
5. Mably TA, Bjerke DL, Moore RW, Gendron-Fitzpatrick A, Peterson RE. In utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin. 3. Effects on spermatogenesis and reproductive capability. Toxicol Appl Pharmacol. 1992;114:118-26.
6. Walters LM, Rourke AW, Eroschenko VP. Purified methoxychlor stimulates the reproductive tract in immature female mice. Reprod Toxicol. 1993;7:599-606.
7. Kaldas RS, Hughes CL Jr. Reproductive and general metabolic effects of phytoestrogens in mammals. Reprod Toxicol. 1989;3:81-9.
8. McLachlan JA. Functional toxicology: a new approach to detect biologically active xenobiotics. Environ Health Perspect. 1993;101: 386-7.
9. Walker BE. Animal models of prenatal exposure to diethylstilbestrol. In: Napalkov NP, Rice JM, Tomatis L, Yamasaki H, eds. Perinatal and Multigeneration Carcinogenesis. Lyon: International Agency for Research on Cancer; 1989:349-64.
10. Dodds EC, Goldberg L, Lawson W, Robinson R. Estrogenic activity of certain synthetic compounds. Nature. 1938;141:247-8.
11. Morrell JA. Summary of some clinical reports on stilbestrol. J Clin Endocrinol. 1941;1:419-3.
12. Smith OW, Smith GV. The influence of diethylstilbestrol on the progress and outcome of pregnancy as based on a comparison of treated with untreated primigravidas. Am J Obstet Gynecol. 1949;58: 994-1009.
13. Smith OW, Smith GV. Use of diethylstilbestrol to prevent fetal loss from complications of late pregnancy. N Engl J Med. 1949;241:562-8.
14. Noller KL, Fish CR. Diethylstilbestrol usage: its interesting past, important present, and questionable future. Med Clin North Am. 1974;58:739-810.
15. Dieckmann WJ, Davis ME, Rynkiewicz LM, Pottinger RE. Does the administration of diethylstilbestrol during pregnancy have therapeutic value? Am J Obstet Gynecol. 1953;66:1062-81.
16. Brackbill Y, Berendes HW. Dangers of diethylstilbestrol: review of a 1953 paper [Letter]. Lancet. 1978;2:520.
17. Swyer GIM, Law R. An evaluation of the prophylactic ante-natal use of stilboestrol. Preliminary report. Proceedings of the Society of Endocrinology. 1953;10:vi-vii.
18. Report to the Medical Research Council by their Conference on Diabetes and Pregnancy. The use of hormones in the management of pregnancy in diabetics. Lancet. 1955;269:833-6.
19. Ferguson JH. Effect of stilbestrol on pregnancy compared to the effect of a placebo. Am J Obstet Gynecol. 1953;65:592-601.
20. Berendes HW, Lee YJ. Suspended judgment. The 1953 clinical trial of diethylstilbestrol during pregnancy: could it have stopped DES use? Control Clin Trials 1993;14:179-82.
21. Herbst AL, Scully RE. Adenocarcinoma of the vagina in adolescence. A report of 7 cases including 6 clear-cell carcinomas (so-called mesonephromas). Cancer. 1970;25:745-7.
22. Herbst AL, Ulfelder H, Poskanzer DC. Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med. 1971;284:878-81.
23. Greenwald P, Barlow JJ, Nasca PC, Burnett WS. Vaginal cancer after maternal treatment with synthetic estrogens. N Engl J Med. 1971;285:390-2.
24. Hill EC. Clear cell carcinoma of the cervix and vagina in young women. A report of six cases with association with maternal stilbestrol therapy and adenosis of the vagina. Am J Obstet Gynecol. 1973;116:470-84.
25. Henderson BE, Benton BD, Weaver PT, Linden G, Nolan JF. Stilbestrol urogenital-tract cancer in adolescents and young adults. N Engl J Med. 1973;288:354-8.
26. United States Food and Drug Administration. PDA drug experience monthly bulletin. Diethylstilbestrol Contraindicated in Pregnancy. Washington, D.C.: U.S. Department of Health, Education and Welfare; 1971.
27. Metzler M. The metabolism of diethylstilbestrol. CRC Crit Rev Biochem. 1981;10:171-212.
28. Marselos M, Tomatis L. Diethylstilboestrol: II, pharmacology, toxicology and carcinogeniciyt in experimental animals. Eur J Cancer. 1993;29A:149-55.
29. Marselos M, Tomatis L. Diethylstilboestrol: I, Pharmacology, toxicology and carcinogenesis in humans. Eur J Cancer 1992;28A:1182-9.
30. Shah HC, McLachlan JA. The fate of diethylstilbestrol in the pregnant mouse. J Pharmacol Exp Ther. 1976;197:687-96.
31. Maydl R, Newbold RR, Metzler M, McLachlan JA. Diethylstilbestrol metabolism by the fetal genital tract. Endocrinology. 1983;113:146-51.
32. Endo S, Kodama S, Newbold R, McLachlan J, Barrett JC. Cytogenetic analysis of murine cell lines from diethylstilbestrol-induced uterine endometrial adenocarcinomas. Cancer Genet Cytogenet. 1994;74: 99-103.
33. Waggoner SE, Anderson SM, Van Eyck S, Fuller J, Luce MC, Herbst AL. Human papillomavirus detection and p53 expression in clear-cell adenocarcinoma of the vagina and cervix. Obstet Gynecol. 1994;84: 404-8.
34. Stone R. DES surprises medical researchers again. Science. 1993;259: 1815.
35. Labarthe D, Adam E, Noller KL, O'Brien PC, Robboy SJ, Tilley BC, et al. Design and preliminary observations of the National Cooperative Diethylstilbestrol Adenosis (DESAD) Project. Obstet Gynecol. 1978;51:453-8.
36. Greenberg ER, Barnes AB, Resseguie L, Barrett JA, Burnside S, Lanza LL, et al. Breast cancer in mothers given diethylstilbestrol in pregnancy. N Engl J Med. 1984;311:1393-8.
37. Hadjimichael OC, Meigs JW, Falcier FW, Thompson WD, Flannery JT. Cancer risk among women exposed to exogenous estrogens during pregnancy. J Natl Cancer Inst. 1984;73:831-4.
38. Veridiano NP, Delke I, Rogers J, Tancer ML. Reproductive performance of DES-exposed female progeny. Obstet Gynecol. 1981;58:58-61.
39. Coscrove MD, Benton B, Henderson BE. Male genitourinary abnormalities and maternal diethylstilbestrol. J Urol. 1977;177:220-2.
40. Vessey MP, Fairweather DV, Norman-Smith B, Buckley J. A randomized double-blind controlled trial of the value of stilboestrol therapy in pregnancy: long-term follow-up of mothers and their offspring. Br J Obstet Gynecol. 1983;90:1007-17.
41. Herbst AL, Kurman RJ, Scully RE. Clear-cell adenocarcinomas of the genital tract in young females. Registry report. N Engl J Med. 1972;287:1259-64.
42. Herbst AL, Anderson D. Clear cell adenocarcinoma of the vagina and cervix secondary to intrauterine exposure to diethylstilbestrol. Semin Surg Oncol. 1990;6:343-6.
43. Bibbo M, Haenszel WM, Wied GL, Hubby M, Herbst AL. A twenty-five-year follow-up study of women exposed to diethylstilbestrol during pregnancy. N Engl J Med. 1978;298:763-7.
44. Beral V, Colwell L. Randomised trial of high doses of stilboestrol and ethisterone in pregnancy: long-term follow-up of mothers. Br Med J. 1980;281:1098-101.
45. Colton T, Greenberg ER, Noller K, Resseguie L, Van Bennekom C, Heeren T, et al. Breast cancer in mothers prescribed diethylstilbestrol in pregnancy. Further follow-up. JAMA. 1993;269:2096-100.
46. Greenberg ER, Barnes AB, Resseguie L, Barrett JA, Burnside S, Lanza LL, et al. Breast cancer in mothers given diethylstilbestrol in pregnancy. N Engl J Med. 1984;311:1393-8.
47. Sharp GB, Cole P. Vaginal bleeding and diethylstilbestrol exposure during pregnancy: relationship to genital tract clear cell adenocarcinoma and vaginal adenosis in daughters. Am J Obstet Gynecol. 1990;162:994-1001.
48. Herbst AL, Cole P, Norusis MJ, Welch WR, Scully RE. Epidemiologic aspects and factors related to survival in 384 Registry cases of clear cell adenocarcinoma of the vagina and cervix. Am J Obstet Gynecol. 1979;135:876-86.
49. Melnick S, Cole P, Anderson D, Herbst A. Rates and risks of diethylstilbestrol-related clear-cell adenocarcinoma of the vagina and cervix. An update. N Engl J Med. 1987;316:514-6.
50. Goodman A, Sullinger JC, Rice LW, Fuller AF Jr. Clear cell adenocarcinoma of the vagina: a second primary in a diethylstilbestrol-exposed woman? Gynecol Oncol. 1991;43:173-7.
51. Herbst AL, Anderson S, Hubby MM, Haenszel WM, Kaufman RH, Noller KL. Risk factors for the development of diethylstilbestrol-associated clear cell adenocarcinoma: a case-control study. Am J Obstet Gynecol. 1986;154:814-22.
52. Sharp GB, Cole P. Identification of risk factors for diethylstilbestrol-associated clear cell adenocarcinoma of the vagina: similarities to endometrial cancer. Am J Epidemiol. 1991;134:1316-24.
53. Horwitz RI, Viscoli CM, Merino M, Brennan TA, Flannery JT, Robboy SJ. Clear cell adenocarcinoma of the vagina and cervix: incidence, undetected disease, and diethylstilbestrol. J Clin Epidemiol. 1988;41:593-7.
54. Heimerhorst TJ, Wijnen HJ, Kenemans P, Tjioe GS, Dijkhuizen HH, Calame JJ, et al. Colposcopic findings and intraepithelial neoplasia in diethylstilbestrol-exposed offspring. The Dutch experience. Am J Obstet Gynecol. 1989;161:1191-4.
55. Robboy SJ, Szyfelbein WM, Goellner JR, Kaufman RH, Taft PD, Richard RM, et al. Dysplasia and cytologic findings in 4,589 young women enrolled in diethylstilbestrol-adenosis (DESAD) project. Am J Obstet Gynecol. 1981;140:579-86.
56. Robboy SJ, Kaufman RH, Prat J, Welch WR, Gaffey T, Scully RE, et al. Pathologic findings in young women enrolled in the National Cooperative Diethylstilbestrol Adenosis (DESAD) project. Obstet Gynecol. 1979;53:309-17.
57. Robboy SJ, Welch WR, Young RH, Truslow GY, Herbst AL, Scully RE. Topographic relation of cervical ectropion and vaginal adenosis to clear cell adenocarcinoma. Obstet Gynecol. 1982;60:546-51.
58. Noller KL, Townsend DE, Kaufman RH, Barnes AB, Robboy SJ, Fish CR, et al. Maturation of vaginal and cervical epithelium in women exposed in utero to diethylstilbestrol (DESAD Project). Am J Obstet Gynecol. 1983;146:279-85.
59. Frank AR, Krumholz BA, Deutsch S. Regression of cervicovaginal abnormalities in DBS-exposed women. A comparison of changes in sexually inactive women and the effects of the onset of sexual activity. J Reprod Med. 1985;30:400-3.
60. O'Brien PC, Noller KL, Robboy SJ, Barnes AB, Kaufman RH, Tilley BC, et al. Vaginal epithelial changes in young women enrolled in the National Cooperative Diethylstilbestrol Adenosis (DESAD) project. Obstet Gynecol. 1979;53:300-8.
61. Robboy SJ, Noller KL, O'Brien P, Kaufman RH, Townsend D, Barnes AB, et al. Increased incidence of cervical and vaginal dysplasia in 3,980 diethylstilbestrol-exposed young women. Experience of the National Collaborative Diethylstilbestrol Adenosis Project. JAMA. 1984; 252:2979-83.
62. Faber K, Jones M, Tarraza HM Jr. Invasive squamous cell carcinoma of the vagina in a diethylstilbestrol-exposed woman. Gynecol Oncol. 1990;37:125-8.
63. Walker AH, Ross RK, Haile RW, Henderson BE. Hormonal factors and risk of ovarian germ cell cancer in young women. Br J Cancer. 1988;57:418-22.
64. Seoud MA, Tawfik O, Hunter V. Peritoneal papillary serous carcinoma in a woman with a history of in utero DES exposure. Gynecol Oncol. 1993;50:371-3.
65. Newbold RR, Bullock BC, McLachlan JA. Lesion of the rete testis in mice exposed prenatally to diethylstilbestrol. Cancer Res. 1985;45: 5145-8.
66. Newbold RR, Bullock BC, McLachlan JA. Testicular tumors in mice exposed in utero to diethylstilbestrol. J Urol. 1987;138:1446-50.
67. Bibbo M, Al-Naqeeb M, Baccarini I, Gill W, Newton M, Sleeper KM, et al. Follow-up study of male and female offspring of DES-treated mothers: a preliminary report. J Reprod Med. 1975;15:29-32.
68. Gill WB, Schumacher GFB, Bibbo M, Straus FH 2d, Schoenberg HW. Association of diethylstilbestrol exposure in utero with cryptorchidism, testicular hypoplasia and semen abnormalities. J Urol. 1979;122:36-9.
69. Conley GR, Sant GR, Ucci AA, Mitcheson HD. Seminoma and epididymal cysts in a young man with known diethylstilbestrol exposure in utero. JAMA. 1983;249:1325-6.
70. Leary FJ, Resseguie LJ, Kurland LT, O'Brien PC, Emslander RF, Noller KL. Males exposed in utero to diethylstilbestrol. JAMA. 1984; 252:2984-9.
71. Henderson BE, Benton B, Jing J, Yu MC, Pike MC. Risk factors for cancer of the testis in young men. Int J Cancer. 1979;23:598-602.
72. Schottenfeld D, Warshauer ME, Sherlock S, Zauber AG, Leder M, Payne R. The epidemiology of testicular cancer in young adults. Am J Epidemiol. 1980;112:232-46.
73. Depue RH, Pike MC, Henderson BE. Estrogen exposure during gestation and risk of testicular cancer. J Natl Cancer Inst. 1983;71: 1151-5.
74. Brown LM, Pottern LM, Hoover RN. Prenatal and perinatal risk factors for testicular cancer. Cancer Res. 1986;46:4812-6.
75. Moss AR, Osmond D, Bacchetti P, Torti FM, Gurgin V. Hormonal risk factors in testicular cancer. A case-control study. Am J Epidemiol. 1986;124:39-52.
76. Gershman ST, Stolley PD. A case-control study of testicular cancer using Connecticut tumor registry data. Int J Epidemiol. 1988;17:738-42.
77. Kaufman RH, Adam E. Genital tract anomalies associated with in utero exposure to diethylstilbestrol. Isr J Med Sci. 1978;14:353-62.
78. Kaufman RH, Adam E, Binder GL. Gerthoffer E. Upper genital tract changes and pregnancy outcome in offspring exposed in utero to diethylstilbestrol. Am J Obstet Gynecol. 1980;137:299-308.
79. Kaufman RH, Adam E, Noller K, Irwin JF, Gray M. Upper genital tract changes and infertility in diethylstilbestrol-exposed women. Am J Obstet Gynecol. 1986;154:1312-8.
80. Bibbo M, Gill WB, Azizi F, Blough R, Fang VS, Rosenfleld RL, et al. Follow-up study of male and female offspring of DES-exposed mothers. Obstet Gynecol. 1977;49:1-8.
81. Senekjian EK, Potkul RK, Frey K, Herbst AL. Infertility among daughters either exposed or not exposed to diethylstilbestrol. Am J Obstet Gynecol. 1988;158:493-8.
82. Barnes AB, Colton T, Gundersen J, Noller KL, Tilley BC, Strama T, et al. Fertility and outcome of pregnancy in women exposed in utero to diethylstilbestrol. N Engl J Med. 1980;302:609-13.
83. Wu CH, Mangan CE, Burtnett MM, Mikhail G. Plasma hormones DES-exposed females. Obstet Gynecol. 1980;55:157-62.
84. Peress MR, Tsai CC, Mathur RS, Williamson HO. Hirsutism and menstrual patterns in women exposed to diethylstilbestrol in utero. Am J Obstet Gynecol. 1982;144:135-9.
85. Assies J. Hyperprolactinemia in diethylstilboestrol-exposed women [Letter]. Lancet. 1991;337:983.
86. Hornsby PP, Wilcox AJ, Weinberg CR, Herbst AL. Effects on the menstrual cycle of in utero exposure to diethylstilbestrol. Am J Obstet Gynecol. 1994;170:709-15.
87. Karande VC, Lester RG, Muasher SJ, Jones DL, Acosta AA, Jones HW Jr. Are implantation and pregnancy outcome impaired in diethylstilbestrol-exposed women after in vitro fertilization and embryo transfer? Fertil Steril. 1990;54:287-91.
88. Haney AF. The reproductive consequences of prenatal DES exposure. In: Giusti RM, ed. Report of the NIH Workshop on Long-Term Effects of Exposure to Diethylstilbestrol (DES). Washington, D.C.: U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health; 1992:46-9.
89. Swan SH. Pregnancy outcome in DES daughters. In: Giusti RM, ed. Report of the NIH Workshop on Long-Term Effects of Exposure to Diethylstilbestrol (DES). Washington, D.C.: U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health; 1992:42-9.
90. Driscoll SG, Taylor SH. Effects of prenatal maternal estrogen on the male urogenital system. Obstet Gynecol. 1980;56:537-42.
91. Stenchever MA, Williamson RA, Leonard J, Karp LE, Ley B, Shy K, et al. Possible relationship between in utero diethylstilbestrol exposure and male fertility. Am J Obstet Gynecol. 1981;140:186-91.
92. Whitehead ED, Leiter E. Genital abnormalities and abnormal semen analyses in male patients exposed to diethylstilbestrol in utero. J Urol. 1981;125:47-50.
93. Blair PB. Immunological consequences of early exposure of experimental rodents to diethylstilbestrol and steroid hormones. In: Bern HA, Herbst AL, eds. Developmental Effects of Diethylstilbestrol (DES) in Pregnancy. New York: Thieme-Stratton; 1981:167-78.
94. Ways SC, Mortola JF, Zvaifler NJ, Weiss RJ, Yen SS. Alterations in immune responsiveness in women exposed to diethylstilbestrol in utero. Fertil Steril. 1987;48:193-7.
95. Ford CD, Johnson GH, Smith WG. Natural killer cells in utero diethylstilbestrol-exposed patients. Gynecol Oncol. 1983;16:400-4.
96. Noller KL, Blair PB, O'Brien PC, Melton LJ 3d, Offord JR, Kaufman RH, et al. Increased occurrence of autoimmune disease among women exposed in utero to diethylstilbestrol. Fertil Steril. 1988;49: 1080-2.
97. Blair PB. Immunologic consequences of prenatal exposure to hormones: DES and the human female. In: Giusti RM, ed. Report of the NIH Workshop on Long-Term Effects of Exposure to Diethylstilbestrol (DES). Washington, D.C: U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health; 1992:30-1.
98. Hines M, Alsum P, Gorski RA, Goy RW. Prenatal exposure to estrogen masculinizes and defeminizes behavior in the guinea pig. Abstracts. Society for Neuroscience. 1982;8:196.
99. Hines M, Goy RW. Estrogens before birth and development of sex-related reproductive traits in the female guinea pig. Horm Behav. 1985;19:331-47.
100. Tarttelin MF, Gorski RA. Postnatal influence of diethylstilbestrol on the differentiation of the sexually dimorphic nucleus in the rat is as effective as perinatal treatment. Brain Res. 1988;456:271-4.
101. Metzler M. Diethylstilbestrol metabolism in humans and experimental animals. In: Herbst AL, Bern HA, eds. Developmental Effects of Diethylstilbestrol (DES) in Pregnancy. New York: Thieme-Stratton; 1981:158-66.
102. Fuller GB, Yates DE, Helton ED, Hobson WC. Diethylstilbestrol reversal of gonadotropin patterns in infant rhesus monkeys. J Steroid Biochem. 1981;15:497-500.
103. Newbold RR. Gender-related behavior in women exposed prenatally to diethylstilbestrol. Environ Health Perspect. 1993;101:208-13.
104. Beral V, Colwell L. Randomised trial of high doses of stilboestrol and ethisterone therapy in pregnancy: long-term follow-up of the children. J Epidemiol Commun Health. 1981;35:155-60.
105. Gustavson CR, Gustavson JC, Noller KL, O'Brien PC, Melton LJ, Pumariega AJ, et al. Increased risk of profound weight loss among women exposed to diethylstilbestrol in utero. Behav Neurol Biol. 1991;55:307-12.
106. Mascaro ML. Preconception tort liability: recognizing a strict liability cause of action for DES grandchildren. Am J Law Med. 1991;17:435-55.
107. Turusov VS, Trukhanova LS, Parfenov YD, Tomatis L. Occurrence of tumors in the descendants of CBA male mice prenatally treated with diethylstilbestrol. Int J Cancer. 1992;50:131-5.
108. Walker BE. Tumors of female offspring of mice exposed prenatally to diethylstilbestrol. J Natl Cancer Inst. 1984;73:133-40.
109. Tomatis L. Transgeneration carcinogenesis: a review of the experimental and epidemiological evidence. Jpn J Cancer Res. 1994;85:443-54.
110. Sharp GB, Cole P, Anderson D, Herbst A. Clear cell adenocarcinoma of the lower genital tract. Correlation of mother's recall of diethylstilbestrol exposure with obstetrical records. Cancer. 1990;66:2215-20.
111. Diethylstilbestrol. ACOG Committee Opinion: Committee on Gynecologic Practice. Number 131 - December 1993. Int J Gynaecol Obstet. 1994;44:184.
112. Noller KL. Role of colposcopy in the examination of diethylstilbestrol-exposed women. Obstet Gynecol Clin North Am. 1993 Mar;20: 165-76.
113. Levine RU, Berkowitz KM. Conservative management and pregnancy outcome in diethylstilbestrol-exposed women with and without gross genital tract abnormalities. Am J Obstet Gynecol. 1993;169:1125-9.