Mechanisms of uterine bleeding in postmenopausal patients receiving estrogen alone or with a progestin.

The response of postmenopausal endometrium to cyclic estrogen and progestin and cyclic estrogen alone was studied in 75 biopsies and over 2000 preparations using standard histologic, histochemical, and scanning and transmission electron microscopic techniques. Estrogen and a progestin caused the atrophic endometrium to assume normal proliferative and secretory phases and to develop nucleolar channel systems. Cyclic unopposed estrogen produced unphysiologic responses in the glands, stromal cells, and vessels. The concept of a progestin or progesterone producing a "medical curettage" should be reappraised. Cyclic estrogen and progestin therapy do not cause all the endometrium to desquamate to the basalis layer. The combination therapy is associated with increased glycoprotein production in the gland and stromal cells, and an orderly regression and remodeling of the endometrium upon hormonal withdrawal. Cyclic estrogen alone causes irregular and unpredictable breakdown, which may or may not extend to the basalis. The stimulation of the endometrium by estrogen alone may allow the endometrium to use the majority of its energy for growth, which may lead to hyperplasia and neoplasia.