Effects of progestogens on human endometrium.

The effect of progestogens on endometrium depends on the dosage, duration of exposure, the type of progestogen, and the presence or absence of estrogen. Mechanisms of progestogen action in endometrium are mainly expressed through the binding of hormone to specific nuclear receptors. Exogenous progestogens seem to influence the hypothalamic-pituitary-ovarian-endometrial axis differently in different individuals. Endogenous hormones resulting from ovarian secretion have effects on the endometrium independent of, and in combination with, exogenous progestogens. Endometrial morphological changes with progestogens vary from suppression of endometrial glandular growth, through stromal decidualization and leukocytic infiltration to glandular atrophy and stromal focal necrosis. In a minority of cases resulting from very prolonged treatment connective tissue fibers increase to some degree and may be accompanied by endometrial fibrosis and calcification. Clinical and histological data have demonstrated that all these changes, including fibrosis and calcification, return to normal in a short period after discontinuing treatment. Endometrial changes during progestogen therapy are often accompanied by leukocyte infiltration, especially when necrosis occurs. White blood cells constitute an important component of normal endometrium. The number and the type of leukocytes change during the normal menstrual cycle apparently related to circulating ovarian hormonal changes. Exogenous progestogens also influence white blood cells, by increasing total numbers and certain specific cell types. Changes in endometrial white blood cell function as a consequence of exogenous progestogens are unclear, but it is possible that the increase of leukocyte infiltration resulting from exogenous progestogens plays an important role in evoking progestational endometrial necrosis.