Risk of endometrial cancer following estrogen replacement with and withoutprogestins

Background: Unopposed estrogen replacement therapy (i.e., estrogen without progestins) increases the risk of endometrial cancer. In this study, we exa mined the endometrial cancer risk associated with combined estrogen-progest in regimens currently in use, since the safety profiles of these regimens h ave not been clearly defined. Methods: We conducted a nationwide population -based, case-control study in Sweden of postmenopausal women aged 50-74 yea rs. We collected information on use of hormone replacement from 709 case pa tients with incident endometrial cancer and from 3368 control subjects. We used unconditional logistic regression to calculate odds ratios (ORs) as es timates of relative risks. All individual comparisons were made with women who never used the respective hormone replacement regimens. Results: Treatm ent with estrogens alone was associated with a marked duration- and dose-de pendent increase in the relative risk of endometrial cancer. Five or more y ears of treatment had an OR of 6.2 for estradiol (95% confidence interval [ CI] = 3.1-12.6) and of 6.6 for conjugated estrogens (95% CI = 3.6-12.0). Fo llowing combined estrogen-progestin use, the association was considerably w eaker than that for estrogen alone; the OR was 1.6 (95% CI = 1.1-2.4) after 5 or more years of use. This increase in risk was confined to women with c yclic use of progestins, i.e., fewer than 16 days per cycle (most commonly 10 days per cycle [OR = 2.9; 95% CI = 1.8-4.6 for 5 or more years of use]), whereas continuous progestin use along with estrogens was associated with a reduced risk (OR = 0.2; 95% CI = 0.1-0.8 for 5 or more years of use). Con clusion: The risk of developing endometrial cancer is increased after long- term use of estrogens without progestins and with cyclically added progesti ns. Continuously added progestins may be needed to minimize the endometrial cancer risk associated with estrogen replacement therapy.