Sex hormones, anti-honnones and adenocarcinoma of the endometrium

Endometrioid adenocarcinoma of the endometrium is a hormone-dependent disease. Estrogens act, after binding to the estrogen receptor, as transcription factors with direct activation of various cell regulatory genes that induce mitosis and thus proliferation. Unopposed, uninterrupted estrogen stimulation results clinically in endometrial proliferation, increased ultrasonographic Double-Layer Endothelial Thickness (DET), hyperplasia and bleeding. An incessant high mitotic activity leads to accumulation of DNA replication errors, which, when not repaired, could result in a malignant phenotype, atypical hyperplasia and invasive cancer. Therefore, in postmenopausal women endometrial neoplasia should be prevented by adequate opposition through the addition of a progestagen, daily or at least 12 days each month. In premenopausal women, with a desire for future childbearing, progestogen based reversion of hyperplasia, and even early cancer, can be obtained in a substantial proportion of patients. In the future, new anti-estrogens like fulvestrant could play a role in the non-surgical treatment of endometrial cancer, in those situations where surgery is precluded. (c) 2005 Elsevier B.V. All rights reserved.