Our case–control study of the relation between estrogen use and endometrial cancer involved 451 cases and 888 controls. The overall risk of endometrial carcinoma was six-fold for estrogen users as compared with nonusers; long-term users (> five years) had a 15-fold risk. Excess risk was present for both diethylstilbestrol and conjugated estrogens. The risk associated with cyclic use was as great as that for continuous use. Increased risk was associated with estrogen use for all histologic grades of the tumor. The risk of advanced-stage carcinoma was fourfold for estrogen users, but the confidence interval was wide, and this question requires further study. Finally, this investigation contradicts the speculation that the association between this cancer and estrogen use can be explained by swifter diagnosis for estrogen users, misclassification of estrogen-related hyperplasia or treatment of early symptoms of the tumor with estrogen. (N Engl J Med 300:9–13, 1979) A NUMBER of case–control (retrospective) studies have reported an association between use of estrogens in the menopause and subsequent development of cancer of the uterine corpus.1 2 3 4 5 Despite different types of controls and dissimilar methods of ascertaining estrogen exposure, the findings have been generally consistent, yielding relative-risk estimates of about four to eight associated with estrogen use. However, serious criticisms have been made concerning prior investigations, which we summarize as follows: The first is that diagnostic surveillance is not taken into account. This view holds that the association between estrogen use and uterine cancer may be spurious owing to the increased.
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