Long-term use of postmenopausal estrogen and progestin hormone therapies and the risk of endometrial cancer.

Objective: The purpose of this study was to assess whether endometrial cancer risk among long-term users of (1) sequential estrogen plus progestin 10-24 days per month exceeds that of nonusers and (2) daily estrogen plus progestin (continuous combined hormone therapy) is below that of nonusers.

Study Design: In this population-based case-control study with 1038 endometrial cancer cases diagnosed in 1985-1999 and 1453 control subjects, exclusive users of a single form of hormone therapy were compared with never users of hormone therapy.

Results: For sequential therapy, only long-term use (> or = 6 years) was associated with increased risk (odds ratio, 2.0; 95% CI, 1.2-3.5). Continuous combined therapy was associated with decreased risk (odds ratio, 0.59; 95% CI, 0.40-0.88), with no increased risk among long-term users (odds ratio, 0.77; 95% CI, 0.45-1.3).

Conclusion: These results support the hypotheses that continuous combined therapy does not increase (and may decrease) endometrial cancer risk and that long-term sequential therapy can lead to a modest increased risk. However, the collective results of all studies of these questions and their clinical implications remain unclear.