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Journal of Epidemiology and Community Health logoLink to Journal of Epidemiology and Community Health
. 1981 Sep;35(3):155–160. doi: 10.1136/jech.35.3.155

Randomised trial of high doses of stilboestrol and ethisterone therapy in pregnancy: long-term follow-up of the children.

V Beral, L Colwell
PMCID: PMC1052149  PMID: 7035598

Abstract

The 27-year follow-up is reported of 136 children whose mothers were involved in a randomised trial of high doses of stilboestrol and ethisterone therapy during pregnancy. The children were not contacted directly. Information about them was obtained from hospitals, general practitioners, and other official sources; and the persons who responded to our inquiries were unaware of who had been exposed to hormones in utero and whose mothers had received an inactive tablet. All children were traced. Urogenital anomalies were reported more frequently in the hormone-exposed than the unexposed children (14% and 9% respectively). The earlier in pregnancy the therapy began, the higher the prevalence rate of abnormalities (X2 for trend, p less than 0.02). No malignant tumours were reported. For males, the proportion reported to be married or living as married was lower in the exposed than in the unexposed group (32% and 62% respectively). The proportion was lower the earlier in pregnancy hormonal exposure occurred and the higher the total hormone dose to which they were exposed (X2 for trend, p less than 0.02). These findings suggest that some interference with sexual function may not be uncommon in males exposed to high doses of stilboestrol and ethisterone while in utero.

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Selected References

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  1. Barnes A. B., Colton T., Gundersen J., Noller K. L., Tilley B. C., Strama T., Townsend D. E., Hatab P., O'Brien P. C. Fertility and outcome of pregnancy in women exposed in utero to diethylstilbestrol. N Engl J Med. 1980 Mar 13;302(11):609–613. doi: 10.1056/NEJM198003133021105. [DOI] [PubMed] [Google Scholar]
  2. Barnes A. B. Menstrual history of young women exposed in utero to diethylstilbestrol. Fertil Steril. 1979 Aug;32(2):148–153. [PubMed] [Google Scholar]
  3. 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 Oct 25;281(6248):1098–1101. doi: 10.1136/bmj.281.6248.1098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bibbo M., Al-Naqeeb M., Baccarini I., Gill W., Newton M., Sleeper K. M., Sonek R. N., Wied G. L. Follow-up study of male and female offspring of DES-treated mothers a preliminary report. J Reprod Med. 1975 Jul;15(1):29–32. [PubMed] [Google Scholar]
  5. Coscrove M. D., Benton B., Henderson B. E. Male genitourinary abnormalities and maternal diethylstilbestrol. J Urol. 1977 Feb;117(2):220–222. doi: 10.1016/s0022-5347(17)58407-4. [DOI] [PubMed] [Google Scholar]
  6. DIECKMANN W. J., DAVIS M. E., RYNKIEWICZ L. M., POTTINGER R. E. Does the administration of diethylstilbestrol during pregnancy have therapeutic value? Am J Obstet Gynecol. 1953 Nov;66(5):1062–1081. doi: 10.1016/s0002-9378(16)38617-3. [DOI] [PubMed] [Google Scholar]
  7. Ehrhardt A. A. Behavioral effects of estrogen in the human female. Pediatrics. 1978 Dec;62(6 Pt 2):1166–1170. [PubMed] [Google Scholar]
  8. Gal I., Kirman B., Stern J. Hormonal pregnancy tests and congenital malformation. Nature. 1967 Oct 7;216(5110):83–83. doi: 10.1038/216083a0. [DOI] [PubMed] [Google Scholar]
  9. Gill W. B., Schumacher G. F., Bibbo M. Pathological semen and anatomical abnormalities of the genital tract in human male subjects exposed to diethylstilbestrol in utero. J Urol. 1977 Apr;117(4):477–480. doi: 10.1016/s0022-5347(17)58502-x. [DOI] [PubMed] [Google Scholar]
  10. Greenberg G., Inman W. H., Weatherall J. A., Adelstein A. M., Haskey J. C. Maternal drug histories and congenital abnormalities. Br Med J. 1977 Oct 1;2(6091):853–856. doi: 10.1136/bmj.2.6091.853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Harlap S., Prywes R., Davies A. M. Letter: Birth defects and oestrogens and progesterones in pregnancy. Lancet. 1975 Mar 22;1(7908):682–683. doi: 10.1016/s0140-6736(75)91784-5. [DOI] [PubMed] [Google Scholar]
  12. Heinonen O. P., Slone D., Monson R. R., Hook E. B., Shapiro S. Cardiovascular birth defects and antenatal exposure to female sex hormones. N Engl J Med. 1977 Jan 13;296(2):67–70. doi: 10.1056/NEJM197701132960202. [DOI] [PubMed] [Google Scholar]
  13. Herbst A. L., Cole P., Colton T., Robboy S. J., Scully R. E. Age-incidence and risk of diethylstilbestrol-related clear cell adenocarcinoma of the vagina and cervix. Am J Obstet Gynecol. 1977 May 1;128(1):43–50. doi: 10.1016/0002-9378(77)90293-9. [DOI] [PubMed] [Google Scholar]
  14. Herbst A. L., Cole P., Norusis M. J., Welch W. R., Scully R. E. 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 Dec 1;135(7):876–886. doi: 10.1016/0002-9378(79)90814-7. [DOI] [PubMed] [Google Scholar]
  15. Herbst A. L., Ulfelder H., Poskanzer D. C. Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med. 1971 Apr 15;284(15):878–881. doi: 10.1056/NEJM197104222841604. [DOI] [PubMed] [Google Scholar]
  16. Janerich D. T., Piper J. M., Glebatis D. M. Oral contraceptives and congenital limb-reduction defects. N Engl J Med. 1974 Oct 3;291(14):697–700. doi: 10.1056/NEJM197410032911403. [DOI] [PubMed] [Google Scholar]
  17. KAPLAN N. M. Male pseudohermaphrodism: report of a case, with observations on pathogenesis. N Engl J Med. 1959 Sep 24;261:641–644. doi: 10.1056/NEJM195909242611303. [DOI] [PubMed] [Google Scholar]
  18. Kinlen L. J., Badaracco M. A., Moffett J., Vessey M. P. A survey of the use of oestrogens during pregnancy in the United Kingdom and of the genito-urinary cancer mortality and incidence rates in young people in England and Wales. J Obstet Gynaecol Br Commonw. 1974 Nov;81(11):849–855. doi: 10.1111/j.1471-0528.1974.tb00395.x. [DOI] [PubMed] [Google Scholar]
  19. Meyer-Bahlburh H. F. Behavioral effects of estrogen treatment in human males. Pediatrics. 1978 Dec;62(6 Pt 2):1171–1177. [PubMed] [Google Scholar]
  20. Mills J. L., Bongiovanni A. M. Effect of prenatal estrogen exposure on male genitalia. Pediatrics. 1978 Dec;62(6 Pt 2):1160–1165. [PubMed] [Google Scholar]
  21. Monaghan J. M., Sirisena L. A. Stilboestrol and vaginal clear-cell adenocarcinoma syndrome. Br Med J. 1978 Jun 17;1(6127):1588–1590. doi: 10.1136/bmj.1.6127.1588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Noller K. L., Fish C. R. Diethylstilbestrol usage: Its interesting past, important present, and questionable future. Med Clin North Am. 1974 Jul;58(4):793–810. doi: 10.1016/s0025-7125(16)32122-8. [DOI] [PubMed] [Google Scholar]
  23. Nomura T., Kanzaki T. Induction of urogenital anomalies and some tumors in the progeny of mice receiving diethylstilbestrol during pregnancy. Cancer Res. 1977 Apr;37(4):1099–1104. [PubMed] [Google Scholar]
  24. SHEARMAN R. P., GARRETT W. J. Double-blind study of effect of 17-hydroxyprogesterone caproate on abortion rate. Br Med J. 1963 Feb 2;1(5326):292–295. doi: 10.1136/bmj.1.5326.292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Shepherd J. H., Dewhurst J., Pryse-Davies J. Cervical carcinoma-in-situ in woman exposed to diethylstilboestrol in utero. Br Med J. 1979 Jul 28;2(6184):246–246. doi: 10.1136/bmj.2.6184.246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Yalom I. D., Green R., Fisk N. Prenatal exposure to female hormones. Effect on psychosexual development in boys. Arch Gen Psychiatry. 1973 Apr;28(4):554–561. doi: 10.1001/archpsyc.1973.01750340080013. [DOI] [PubMed] [Google Scholar]

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