Long-term use of continuous-combined estrogen-progestin hormone therapy and risk of endometrial cancer

The daily administered dose of progestin in continuous-combined estrogen-progestin therapy is provided to counteract the proliferative effect of estrogen on the postmenopausal endometrium. However, there remains some uncertainty as to whether use of such a combined regimen, over the long term, is associated with an altered risk of endometrial cancer. We pooled data from four population-based case–control studies of endometrial cancer in western Washington State. Cases, ages 45–74, were diagnosed between 1985 and 2005. Using logistic regression with the adjustment for confounding factors, women who had exclusively used continuous-combined estrogen-progestin therapy (90 endometrial cancer cases, 227 controls) were compared with women who had never used any type of hormone therapy (774 cases, 1,116 controls). Associations with duration and recency of use were evaluated overall and within strata defined by body mass index. Long-term use of continuous-combined estrogen-progestin therapy (≥10 years) was associated with a reduced risk of endometrial cancer (OR = 0.37, 95% CI: 0.21–0.66). This association was most pronounced in women with a body mass index ≥30 kg/m² (OR = 0.19, 95% CI: 0.05–0.68). Associations did not differ according to recency of use. These results suggest that long duration of use of continuous-combined estrogen-progestin therapy is associated with a reduced risk of endometrial cancer.