Clinical stage and pathological characteristics of endometrial cancer cases were related to several aspects of estrogen prescribing. In comparing 256 cases with 321 community control subjects, estrogen use of less than 3 1/2 years' duration did not increase the risk of endometrial cancer for any stage, grade, histological type, or extent of invasion. With long-term estrogen use (3 1/2 years or more), relative risks were significantly increased (5.2 to 7.6) for the early cancers—those clinically stage IA, histologically grade 1, and invading the endometrium only. These increases were seen with both high-dose (>0.625 mg) and low-dose (≤0.625 mg) preparations. Risks were only minimally increased for the more advanced cancers. However, long-duration estrogen use did produce an increased risk of advanced cancer when administration was continuous rather than cyclic.
(JAMA 244:2419-2422, 1980)
Hulka BS, Kaufman DG, Fowler WC, Grimson RC, Greenberg BG. Predominance of Early Endometrial Cancers After Long-term Estrogen Use. JAMA. 1980;244(21):2419-2422. doi:10.1001/jama.1980.03310210021018