Our aim was to determine the risk of endometrial cancer associated with long-term use of combined hormone therapy (HT) and low-potency estrogens. In this prospective population-based cohort, 40,000 women aged 25-64 years, without prior cancer or hysterectomy, were included. The women answered 2 questionnaires at a 10-year interval regarding HT use and personal details. Women were followed up for an average of 15.5 years through the National Cancer and Causes of Death Registry, representing 236,611 women years. Among the 17,822 postmenopausal women included, 166 cases of endometrial cancer were diagnosed. Only use of combined HT was related to a decreased risk of endometrial cancer (OR 0.3, 95% CI 0.1-0.8), the protective effect was found after 2 years, and increased with extended duration of use. "Only use" of low-potency estrogens increased the risk of endometrial cancer almost to the same extent as use of high-potency estrogens (OR 2.0, 95% CI 1.1-3.6 vs. OR 2.5, 95% CI 1.3-4.8), the increased risk was confined to non-obese women in both groups. The risk was significantly increased for oral but not for local low-potency estrogen users (OR 2.1, 95% CI 1.1-3.6 vs. OR 1.5, 95% CI 0.4-6.2, respectively). In long-term estrogen users the risk was highest during the first 2 years, dropping slightly thereafter. Since low-potency estrogen use increases the risk of endometrial cancer almost as much as high-potency estrogen use, they should only be given if medically indicated.
Adult Cohort Studies