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Source: Weiderpass E, et al. Low-potency oestrogen and risk of endometrial cancer: A case-control study. Lancet 1999;353:1824-1828.
Design and Setting: National population-based, case-control study in Sweden.
Subjects: 789 postmenopausal women with endometrial cancer and 3,368 controls (histopathological review reclassified 80 cancer cases as endometrial atypical hyperplasia).
Results: Five years oral use of estriol 1-2 mg/d increased the relative risk of endometrial cancer compared to never-use; the odds ratio was 3.0 for endometrial cancer and 8.3 for atypical endometrial hyperplasia. Ever-use of estriol was associated with a doubling of endometrial cancer risk compared to never-use. The association was stronger for well-differentiated cancers and excess risk was lost quickly on cessation of treatment. Only weak associations were noted for vaginal use of estriol and risk of endometrial neoplasia.
Funding: Research American Cancer Society grant EDT-89; NIH grant RO-1-CA 58427; grant from the Swedish Cancer Society.
Comments: Low-potency estrogen preparations, including estriol, are popular in Sweden (and are usually prescribed without a progestin). In North America, estriol has been promoted by alternative medicine practitioners as a "safe" estrogen that does not cause endometrial proliferation; claims have even been made that it reduces breast cancer risk. These claims were not based on reliable data. (See Alternative Therapies in Women’s Health, June 1999, pp. 51-52.) Although estriol is weaker and shorter-acting than other estrogens used in hormone replacement therapy (HRT), assumptions of harmlessness were premature. This epidemiological study makes it clear that estriol has a significant adverse effect on endometrial neoplasia and should not be used without a progestin.