Summary
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.
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References
Beral, V. & Colwell, L. (1980). Randomized trial of high doses of stilbestrol and ethisterone in pregnancy: long-term follow-up of mothers. Br Med J 281: 1098–1101.
Beral, V. & Golwell, L. (1981). Randomized trial of high doses of stilboestrol and ethisterone therapy in pregnancy: long-term follow-up of the children. J Epidemiol Commun Health 35: 155–160.
Bibbo, M., Gill, W. M., Azizi, F., Blough, R., Fang, V. S., Rosenfield, R. L., Schumaher, G. F. B., Sleeper, K., Sonek, M. G. & Wied, G. L. (1977). Follow-up study of male and female offspring of DES-exposed mothers. Obstet Gynecol 49: 1–8.
Briggs, G. G., Freeman, R. K. & Yaffe, S. J. (1994). Drugs in Pregnancy and Lactation , 4th Edn, pp. xi, xii. Williams & Wilkins: Baltimore
Colton, T., Greenberg, R., Noller, K., Resseguie, L., Van Bennekom, C., Heeren, T. & Zhang, Y. (1993). Breast cancer in mothers prescribed stilbestrol in pregnancy: further follow-up. JAMA 269: 2096–2100.
Depue, R. H., Pike, M. C. & Henderson, B. E. (1983). Estrogen exposure during gestation and risk of testicular cancer. J Natl Cancer Inst 71: 1151–1155.
Ekbom, A., Trichopoulos, D., Adami, H-O, Hsieh, C-C & Lan, S-J (1992). Evidence of prenatal influences on breast cancer risk. Lancet 340: 1015–1018.
Goldstein, P. A., Sacks, H. S. & Chalmers, T. C. (1989). Hormone administration for the maintenance of pregnancy. In Effective Care in Pregnancy and Childbirth, Chalmers I, Enkin M, Keirse MJNC (eds), pp. 612–623. Oxford University Press: Oxford
Heinonen, O. P., Slone, D. & Shapiro, S. (1977). Birth Defects and Drugs in Pregnancy. Publishing Sciences Group: Littleton, Mass
Jaffe, B., Shye, D., Harlap, S., Baras, M., Belmaker, E., Gordon, L., Magidor, S. & Fortney, J. (1990). Health, growth and sexual development of teenagers exposed in utero to medroxyprogesterone acetate. Pediatric Perinatal Epidemiol 4: 184–195.
La-Vecchia, C., Negri, E., Franceschi, S. & Parazzini, F. (1993). Long-term impact of reproductive factors on cancer risk. Int J Cancer 53: 215–219.
Leon, D. & Ben-Shlomo, Y. (1997). Preadult influences on cardiovascular disease and cancer. In A Life Course Approach to Chronic Disease Epidemiology, Kuh D, Ben-Shlomo Y (eds). Oxford University Press: Oxford
McPherson, C. P., Sellers, T. A., Potter, J. D., Bostick, R. M. & Fosom, A. R. (1996). Reproductive factors and risk of endometrial cancer. The Iowa Women’s Health Study. Am J Epidemiol 143: 1195–1202.
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. (1996). Birthweight as a risk factor for breast cancer. Lancet 348: 1542–1546.
Møller, H. & Skakkebæk, N. E. (1997). Testicular cancer and cryptorchidism in relation to prenatal factors: case-control studies in Denmark. Cancer Causes Control 8: 904–912.
Prener, A., Engholm, G. & Jensen, O. M. (1996). Genital anomalies and risk for testicular cancer in Danish men. Epidemiology 7: 14–19.
Preston-Martin, S. (1989). Epidemiological studies of perinatal carcinogenesis. In Perinatal and Multigeneration Carcinogenesis, Napalkov NP, Rice JM, Tomatis L, Yamasaki H (eds), pp. 289–334. IARC Scientific Publications No 96. IARC: Lyon
Senekjian, E. K., Potkul, R. K., Frey, K. & Herbst, A. L. (1988). Infertility among daughters either exposed or not exposed to diethylstilbestrol. Am J Obstet Gynecol 158: 493–498.
Swerdlow, A. J., De Stavola, B. L., Swanwick, M. A. & Maconochie, N. E. S. (1997a). Risks of breast and testicular cancers in young adult twins in England and Wales: evidence on prenatal and genetic aetiology. Lancet 350: 1723–1728.
Swerdlow, A. J., Higgins, C. D. & Pike, M. C. (1997b). Risk of testicular cancer in cohort of boys with cryptorchidism. Br Med J 314: 1507–1511.
Teppo, L., Pukkala, E. & Lehtonen, M. (1994). Data quality and quality control of a population-based cancer registry. Experience in Finland. Acta Oncol 33: 365–369.
Thomas, H. V., Reeves, G. K. & Key, T. J. A. (1997). Endogenous estrogen and postmenopausal breast cancer: a quantitative review. Cancer Causes Control 8: 922–928.
Vainio, H. (1989). Carcinogenesis and teratogenesis may have common mechanisms. Scand J Work Environ Health 15: 13–17.
Wald, N. J. & Hackshaw, A. K. (1996). Cigarette smoking: an epidemiological overview. Br Med Bull 52: 3–11.
Walsh, R. A. (1994). Effects of maternal smoking on adverse pregnancy outcomes: examination of the criteria of causation. Hum Biol 66: 1059–1092.
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Hemminki, E., Gissler, M. & Toukomaa, H. Exposure to female hormone drugs during pregnancy: effect on malformations and cancer. Br J Cancer 80, 1092–1097 (1999). https://doi.org/10.1038/sj.bjc.6690469
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DOI: https://doi.org/10.1038/sj.bjc.6690469
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