Morphological Effects of Exogenous Gestagens on Abnormal Human Endometrium

Abstract

Progestagens given in appropriate doses and for appropriate time may control endometrial hyperplasia and a certain proportion of carcinoma. Progestagen-induced secretory differentiation is followed by a decrease in DNA-synthesis, arrest in mitosis, prolongation of the tissue turnover time, and an increase in autophagy and cellular and tissue necrosis. Secretory conversion, inhibition of DNA synthesis, and mitosis are features associated with an intact receptor-hormone binding mechanism. Autophagy is a consequence of gestagen-induced secretory activity of epithelial cells, whereas cellular and coagulative necrosis are a reflection of the nonspecific cytotoxic effect of pharmacologic doses of progestagens. The presently available data suggest that hyperplastic and neoplastic endometria are made of a heterogeneous cellular population in which receptor-containing hormone-sensitive cells are admixed with receptor-free, and consequently hormone-insensitive cells. The latter are independent of hormonal influence, grow autonomously and their number presumably increases paralleling the severity of endometrial hyperplasia and carcinoma. They are responsible for recurrences and/or the nonresponsiveness of most adenocarcinomas and atypical hyperplasias to gestagen therapy.