Estrogen Therapy and the Risk of Breast, Ovarian, and Endometrial Cancer

  • Nancy C. Lee
  • Phyllis A. Wingo
  • Herbert B. Peterson
  • George L. Rubin
  • Richard W. Sattin


Millions of women have used estrogens for relief of menopausal symptoms. Theoretical considerations, clinical observations, and epidemiologic information raise concern as to possible associations between use of exogenous estrogens and cancers of the female reproductive tract (Thomas, 1978). Because of the large number of women who have been using or will use estrogens for menopausal symptoms, any risk of or protection from these cancers could have major health impact on women in their postmenopausal years.


Breast Cancer Ovarian Cancer Endometrial Cancer Endometrial Carcinoma Estrogen Therapy 
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  1. Annegers, J. F., Strom, H., Decker, D. G., Dockerty, M. B., and O’Fallon, W. M., 1979, Ovarian cancer: Incidence and case-control study, Cancer 43:723–729.PubMedCrossRefGoogle Scholar
  2. Antunes, C. M. F., Stolley, P. D., Rosenshein, N. B., Davies, J. L., Tonascia, J. A., Brown, C., Burnett, L., Rutledge, A., Pokempner, M., and Garcia, R., 1979, Endometrial cancer and estrogen use: Report of a large case-control study, N. Engl. J. Med. 300:9–13.PubMedCrossRefGoogle Scholar
  3. Boston Collaborative Drug Surveillance Program, 1974, Surgically confirmed gallbladder disease, venous thromboembolism, and breast tumors in relation to postmenopausal estrogen therapy, N. Engl. J. Med. 290:15–18.CrossRefGoogle Scholar
  4. Brinton, L. A., Hoover, R. N., Szklo, M., and Fraumeni, J. F., 1981, Menopausal estrogen use and risk of breast cancer, Cancer 47:2517–2522.PubMedCrossRefGoogle Scholar
  5. Casagrande, J., Gerkins, V., Henderson, B. E., Mack, T., and Pike, M. C., 1976, Brief communication: Exogenous estrogens and breast cancer in women with natural menopause, J. Natl. Cancer Inst. 56:839–841.PubMedGoogle Scholar
  6. Centers for Disease Control Cancer and Steroid Hormone Study, 1983a, Long-term oral contraceptive use and the risk of breast cancer, JAMA 249:1591–1595.CrossRefGoogle Scholar
  7. Centers for Disease Control Cancer and Steroid Hormone Study, 1983b, Oral contraceptive use and the risk of ovarian cancer, JAMA 249:1596–1599.CrossRefGoogle Scholar
  8. Centers for Disease Control Cancer and Steroid Hormone Study, 1983c, Oral contraceptive use and the risk of endometrial cancer, JAMA 249:1600–1604.CrossRefGoogle Scholar
  9. Craig, T. J., Comstock, G. W., and Geiser, P. B., 1974, Epidemiologic comparison of breast cancer patients with early and late onset of malignancy and general population controls, J. Natl. Cancer Inst. 53:1577–1581.PubMedGoogle Scholar
  10. Cramer, D. W., Hutchinson, G. B., Welch, W. R., Scully, R. E., and Ryan, K. J., 1983, Determinants of ovarian cancer risk: I. Reproductive experiences and family history, J. Natl. Cancer Inst. 71:711–716.PubMedGoogle Scholar
  11. Gray, L. A., Christopherson, W. M., and Hoover, R. N., 1977, Estrogens and endometrial carcinoma, Obstet. Gynecol. 49:385–389.PubMedGoogle Scholar
  12. Hildreth, N. G., Kelsey, J. L., LiVolsi, V. A., Fischer, D. B., Holford, T. R., Mostow, E. D., Schwartz, P. E., and White, C., 1981, An epidemiologic study of epithelial carcinoma of the ovary, Am. J. Epidemiol. 114:398–405.PubMedGoogle Scholar
  13. Hoogerland, D. L., Buchler, D. A., Crowley, J. J., and Carr, W. F., 1978, Estrogen use — risk of endometrial carcinoma, Gynecol. Oncol. 6:451–458.PubMedCrossRefGoogle Scholar
  14. Hoover, R., Gray, L. A., Sr, Cole, P., and MacMahon, B., 1976, Menopausal estrogens and breast cancer, N. Engl. J. Med. 295:401–405.PubMedCrossRefGoogle Scholar
  15. Hoover, R., Gray, L. A., Sr, and Fraumeni, J. F., Jr, 1977, Stilboestrol (Diethylstilbestrol) and the risk of ovarian cancer, Lancet 2:533–534.PubMedCrossRefGoogle Scholar
  16. Hoover, R., Glass, A., and Finkle, W. D., et al., 1981, Conjugated estrogens and breast cancer risk in women, J. Natl. Cancer Inst. 67:815–820.PubMedGoogle Scholar
  17. Horwitz, R. I., and Feinstein, A. R., 1978, Alternative analytic methods for the case-control studies of estrogens and endometrial cancer, N. Engl. J. Med. 299:1089–1094.PubMedCrossRefGoogle Scholar
  18. Hulka, B. S., 1980, Effect of exogenous estrogen on postmenopausal women: The epidemiologic evidence, Obstet. Gynecol. Surv. 35:389–399.CrossRefGoogle Scholar
  19. Hulka, B. S., Grimson, R. C., Greenberg, B. G., Kaufman, D. G., Fowler, W. C., Hogue, C. J. R., Berger, G. S., and Pulliam, C. C., 1980, “Alternative” controls in a case-control study of endometrial cancer and exogenous estrogen, Am. J. Epidemiol. 112:376–387.PubMedGoogle Scholar
  20. Hulka, B. S., Chambless, L. E., Deubner, D. C., and Wilkinson, W. E., 1982, Breast cancer and estrogen replacement therapy, Am. J. Obstet. Gynecol. 143:638–644.PubMedGoogle Scholar
  21. Jelovsek, F. R., Hammond, C. B., Woodard, B. H., Draffin, R., Lee, K. L., Creasman, W. T., and Parker, R. T., 1980, Risk of exogenous estrogen therapy and endometrial cancer, Am. J. Obstet. Gynecol. 137:85–91.PubMedGoogle Scholar
  22. Jick, H., Walker, A. M., Watkins, R. N., D’Ewart, D. C., Hunter, J. R., Danford, A., Madsen, S., Dinan, B. J., and Rothman, K. J., 1980, Replacement estrogens and breast cancer, Am. J. Epidemiol. 112:586–594.PubMedGoogle Scholar
  23. Kaufman, D. W., Miller, D. R., Rosenberg, L., Helmrich, S. P., Stolley, P., Schottenfeld, D., and Shapiro, S., 1984, Noncontraceptive estrogen use and the risk of breast cancer, JAMA 252:63–67.PubMedCrossRefGoogle Scholar
  24. Kelsey, J. L., Fischer, D. B., Holford, T. R., LiVolsi, V., Mostow, E. D., Goldenberg, I. S., and White, C., 1981, Exogenous estrogens and other factors in the epidemiology of breast cancer, J. Natl. Cancer Inst. 67:327–333.PubMedGoogle Scholar
  25. Kelsey, J. L., LiVolsi, V. A., Holford, T. R., Fischer, D. B., Mostow, E. D., Schwartz, P.E., O’Connor, T., and White, C., 1982, A case-control study of cancer of the endometrium, Am. J. Epidemiol. 116:333–342.PubMedGoogle Scholar
  26. La Vecchia, C., Liberati, A., and Franceschi, S., 1982, Noncontraceptive estrogen use and the occurrence of ovarian cancer, J. Natl. Cancer Inst. 69:1207.PubMedGoogle Scholar
  27. Mack, T. M., Pike, M. C., Henderson, B. E., Pfeffer, R. I., Gerkins, V. R., Arthur, M., and Brown, S. E., 1976, Estrogens and endometrial cancer in a retirement community, N. Engl. J. Med. 294:1262–1267.PubMedCrossRefGoogle Scholar
  28. McDonald, T. W., Annegers, J. F., O’Fallan, W. M., Dockerty, M. B., Malkasian, G. D., and Kurland, L. T., 1977, Exogenous estrogen and endometrial carcinoma: Case-control and incidence study, Am. J. Obstet. Gynecol. 127:572–580.PubMedGoogle Scholar
  29. McGowan, L., Parent, L., Lednar, W., and Noms, H. J., 1979, The woman at risk for developing ovarian cancer, Gynecol. Oncol. 7:325–344.PubMedCrossRefGoogle Scholar
  30. Paterson, M. E. L., Wade-Evans, T., Sturdee, D. W., Thorn, M. H., and Studd, J. W. W., 1980, Endometrial disease after treatment with oestrogens and progestogens in the climacteric, Br. Med. J. 280:822–824.PubMedCrossRefGoogle Scholar
  31. Ravnihar, B., Seigel, D. G., and Lindtner, J., 1979, An epidemiologic study of breast cancer and benign breast neoplasias in relation to the oral contraceptive and estrogen use, Europ. J. Cancer 15:395–405.CrossRefGoogle Scholar
  32. Ross, R. K., Paganini-Hill, A., Gerkins, V. R., Mack, T. M., Pfeffer, R., Arthur, M., and Henderson, B. E., 1980, A case-control study of menopausal estrogen therapy and breast cancer, JAMA 243:1635–1639.PubMedCrossRefGoogle Scholar
  33. Sartwell, P. E., Arthes, F. G., and Tonascia, J. A., 1977, Exogenous hormones, reproductive history and breast cancer, J. Natl. Cancer Inst. 59:1589–1592.PubMedGoogle Scholar
  34. Shapiro, S., Kaufman, D. W., Slone, D., Rosenberg, L., Miettinen, O. S., Stolley, P. D., Rosenshein, N. B., Watring, W. G., Leavitt, T., and Knapp, R. C., 1980, Recent and past use of conjugated estrogens in relation to adenocarcinoma of the endometrium, N. Engl. J. Med. 303:485–489.PubMedCrossRefGoogle Scholar
  35. Silverberg, E. and Lubera, J. A., 1983, A review of American Cancer Society estimates of cancer cases and deaths, CA 33:2–25.PubMedGoogle Scholar
  36. Smith, D. C., Prentice, R., Thompson, D. J., and Herrmann, W. L., 1975, Association of exogenous estrogen and endometrial carcinoma, N. Engl. J. Med. 293:1164–1167.PubMedCrossRefGoogle Scholar
  37. Spengler, R. F., Clarke, E. A., Woolever, C. A., Newman, A. M., and Osborn, R. W., 1981, Exogenous estrogens and endometrial cancer: A case-control study and assessment of potential biases, Am. J. Epidemiol. 114:497–506.PubMedGoogle Scholar
  38. Stadel, B. V., 1975, The etiology and prevention of ovarian cancer, Am. J. Obstet. Gynecol. 123:772–773.PubMedGoogle Scholar
  39. Stavraky, K. M., Collins, J. A., Donner, A., and Wells, G. A., 1981, A comparison of estrogen use by women with endometrial cancer, gynecologic disorders and other illnesses, Am. J. Obstet. Gynecol. 141:547–555.PubMedGoogle Scholar
  40. Symmers, W. S., 1968, Carcinoma of the breast in transsexual individuals after surgical and hormonal interference with the primary and secondary sex characteristics, Br. Med. J. 2:82.CrossRefGoogle Scholar
  41. Thomas, D. B., 1978, Role of exogenous female hormone in altering the risk of benign and malignant neoplasms in humans, Cancer Res. 38:3991–4000.PubMedGoogle Scholar
  42. Thomas, D. B., 1984, Do hormones cause breast cancer? Cancer 53:595–604.PubMedCrossRefGoogle Scholar
  43. Waksberg, J., 1978, Sampling methods for random digit dialing, J. Am. Stat. Assoc. 73:40–46.CrossRefGoogle Scholar
  44. Weiss, N. S., Lyon, J. L., Krishnamurthy, S., Diftert, S. E., Liff, J. M., and Daling, J. R., 1982, Noncontraceptive estrogen use and the occurrence of ovarian cancer, J. Natl. Cancer Inst. 68:95–98.PubMedGoogle Scholar
  45. Whitehead, M. I., King, R. J. B., McQueen, J., and Cambell, S., 1979, Endometrial histology and biochemistry in climacteric women during oestrogen and oestrogen/progestogen therapy, J. R. Soc. Med. 72:322–327PubMedGoogle Scholar
  46. Ziel, H. K., and Finkel, W. D., 1975, Increased risk of endometrial carcinoma among users of conjugated estrogens, N. Engl. J. Med. 293:1167–1170.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Nancy C. Lee
    • 1
  • Phyllis A. Wingo
    • 1
  • Herbert B. Peterson
    • 1
  • George L. Rubin
    • 1
  • Richard W. Sattin
    • 1
  1. 1.Division of Reproductive Health, Center for Health Promotion and EducationCenters for Disease ControlAtlantaUSA

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