Million Women Study Collaborators: Endometrial cancer and hormone-replacement therapy in the Million Women Study. Lancet 2005;365(9470):1543-51.
Brinton LA, Lacey JV, Trimble EL: Hormones and endometrial cancer-new data from the Million Women Study. Lancet 2005;365(9740):1517-18.(editorial).
Hormone replacement therapy (HRT) containing estrogen alone increases the risk of endometrial cancer in post-menopausal women. To minimize this risk, HRT often consists of combined estrogen-progestagen. In this study in the United Kingdom, 716,738 postmenopausal women without previous cancer or hysterectomy were recruited into the Million Women Study and followed for an average of 3.4 years during which time 1,320 endometrial cancers were detected. Compared with those who never used HRT, risk was reduced with last use of continuous combined preparations (relative risk 0.71, p = 0.005), increased with estrogen only (RR 1.45; p = 0.04), and not significantly changed with last use of cyclic combined preparations (RR =1.05; p = 0.5). Estrogens increased the risk of endometrial cancer, while progestagens counteracted the adverse effect of estrogens on the endometrium. However, current use of combined HRT causes a greater increase in breast cancer than other HRT preparations. Because breast cancer is more common than endometrial cancer (16 vs. 3 per 1,000 women over 5 years respectively), overall cancer incidence increased with the use of combined HRT, both continuous and cyclic. Thus, any benefits for reduced endometrial cancer that may result from continuous combined hormone therapy are far outweighed by increased risks for breast cancer.