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British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Jun;80(7):1092–1097. doi: 10.1038/sj.bjc.6690469

Exposure to female hormone drugs during pregnancy: effect on malformations and cancer

E Hemminki 1, M Gissler 1, H Toukomaa 1
PMCID: PMC2363045  PMID: 10362122

Abstract

This study aimed to investigate whether the use of female sex hormone drugs during pregnancy is a risk factor for subsequent breast and other oestrogen-dependent cancers among mothers and their children and for genital malformations in the children. A retrospective cohort of 2052 hormone-drug exposed mothers, 2038 control mothers and their 4130 infants was collected from maternity centres in Helsinki from 1954 to 1963. Cancer cases were searched for in national registers through record linkage. Exposures were examined by the type of the drug (oestrogen, progestin only) and by timing (early in pregnancy, only late in pregnancy). There were no statistically significant differences between the groups with regard to mothers' cancer, either in total or in specified hormone-dependent cancers. The total number of malformations recorded, as well as malformations of the genitals in male infants, were higher among exposed children. The number of cancers among the offspring was small and none of the differences between groups were statistically significant. The study supports the hypothesis that oestrogen or progestin drug therapy during pregnancy causes malformations among children who were exposed in utero but does not support the hypothesis that it causes cancer later in life in the mother; the power to study cancers in offspring, however, was very low. Non-existence of the risk, negative confounding, weak exposure or low study-power may explain the negative findings. © 1999 Cancer Research Campaign

Keywords: oestrogen, progestin, pregnancy, in-utero, cancer, breast cancer, malformations

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Selected References

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  1. 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]
  2. 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 Community Health. 1981 Sep;35(3):155–160. doi: 10.1136/jech.35.3.155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bibbo M., Gill W. B., Azizi F., Blough R., Fang V. S., Rosenfield R. L., Schumacher G. F., Sleeper K., Sonek M. G., Wied G. L. Follow-up study of male and female offspring of DES-exposed mothers. Obstet Gynecol. 1977 Jan;49(1):1–8. [PubMed] [Google Scholar]
  4. Colton T., Greenberg E. R., Noller K., Resseguie L., Van Bennekom C., Heeren T., Zhang Y. Breast cancer in mothers prescribed diethylstilbestrol in pregnancy. Further follow-up. JAMA. 1993 Apr 28;269(16):2096–2100. [PubMed] [Google Scholar]
  5. Depue R. H., Pike M. C., Henderson B. E. Estrogen exposure during gestation and risk of testicular cancer. J Natl Cancer Inst. 1983 Dec;71(6):1151–1155. [PubMed] [Google Scholar]
  6. Ekbom A., Trichopoulos D., Adami H. O., Hsieh C. C., Lan S. J. Evidence of prenatal influences on breast cancer risk. Lancet. 1992 Oct 24;340(8826):1015–1018. doi: 10.1016/0140-6736(92)93019-j. [DOI] [PubMed] [Google Scholar]
  7. La Vecchia C., Negri E., Franceschi S., Parazzini F. Long-term impact of reproductive factors on cancer risk. Int J Cancer. 1993 Jan 21;53(2):215–219. doi: 10.1002/ijc.2910530207. [DOI] [PubMed] [Google Scholar]
  8. McPherson C. P., Sellers T. A., Potter J. D., Bostick R. M., Folsom A. R. Reproductive factors and risk of endometrial cancer. The Iowa Women's Health Study. Am J Epidemiol. 1996 Jun 15;143(12):1195–1202. doi: 10.1093/oxfordjournals.aje.a008707. [DOI] [PubMed] [Google Scholar]
  9. Michels K. B., Trichopoulos D., Robins J. M., Rosner B. A., Manson J. E., Hunter D. J., Colditz G. A., Hankinson S. E., Speizer F. E., Willett W. C. Birthweight as a risk factor for breast cancer. Lancet. 1996 Dec 7;348(9041):1542–1546. doi: 10.1016/S0140-6736(96)03102-9. [DOI] [PubMed] [Google Scholar]
  10. Møller H., Skakkebaek N. E. Testicular cancer and cryptorchidism in relation to prenatal factors: case-control studies in Denmark. Cancer Causes Control. 1997 Nov;8(6):904–912. doi: 10.1023/a:1018472530653. [DOI] [PubMed] [Google Scholar]
  11. Prener A., Engholm G., Jensen O. M. Genital anomalies and risk for testicular cancer in Danish men. Epidemiology. 1996 Jan;7(1):14–19. doi: 10.1097/00001648-199601000-00004. [DOI] [PubMed] [Google Scholar]
  12. Preston-Martin S. Epidemiological studies of perinatal carcinogenesis. IARC Sci Publ. 1989;(96):289–314. [PubMed] [Google Scholar]
  13. Senekjian E. K., Potkul R. K., Frey K., Herbst A. L. Infertility among daughters either exposed or not exposed to diethylstilbestrol. Am J Obstet Gynecol. 1988 Mar;158(3 Pt 1):493–498. doi: 10.1016/0002-9378(88)90012-9. [DOI] [PubMed] [Google Scholar]
  14. Swerdlow A. J., De Stavola B. L., Swanwick M. A., Maconochie N. E. Risks of breast and testicular cancers in young adult twins in England and Wales: evidence on prenatal and genetic aetiology. Lancet. 1997 Dec 13;350(9093):1723–1728. doi: 10.1016/s0140-6736(97)05526-8. [DOI] [PubMed] [Google Scholar]
  15. Swerdlow A. J., Higgins C. D., Pike M. C. Risk of testicular cancer in cohort of boys with cryptorchidism. BMJ. 1997 May 24;314(7093):1507–1511. doi: 10.1136/bmj.314.7093.1507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Teppo L., Pukkala E., Lehtonen M. Data quality and quality control of a population-based cancer registry. Experience in Finland. Acta Oncol. 1994;33(4):365–369. doi: 10.3109/02841869409098430. [DOI] [PubMed] [Google Scholar]
  17. Thomas H. V., Reeves G. K., Key T. J. Endogenous estrogen and postmenopausal breast cancer: a quantitative review. Cancer Causes Control. 1997 Nov;8(6):922–928. doi: 10.1023/a:1018476631561. [DOI] [PubMed] [Google Scholar]
  18. Vainio H. Carcinogenesis and teratogenesis may have common mechanisms. Scand J Work Environ Health. 1989 Feb;15(1):13–17. doi: 10.5271/sjweh.1889. [DOI] [PubMed] [Google Scholar]
  19. Wald N. J., Hackshaw A. K. Cigarette smoking: an epidemiological overview. Br Med Bull. 1996 Jan;52(1):3–11. doi: 10.1093/oxfordjournals.bmb.a011530. [DOI] [PubMed] [Google Scholar]
  20. Walsh R. A. Effects of maternal smoking on adverse pregnancy outcomes: examination of the criteria of causation. Hum Biol. 1994 Dec;66(6):1059–1092. [PubMed] [Google Scholar]

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