The endometrium of rats under long-term influence of antiprogesterone

Antiprogesterones block the action of progesterone at the receptor level and have profound influences on all progesterone target organs. They are potentially useful in the treatment of hormone dependent cancers and endometriosis and for inhibition of nidation. Several of their therapeutic potentials would require prolonged exposure, and in premenopausal women interactions with endogeneous steroids must be taken into consideration. This paper studies the responses of the endometrium to a long-term treatment with the antiprogesterones Onapristone, ZK 112.993 and Mifepristone in adult rats. In the presence of estrogen, all of the investigated drugs had strong effects on the uterine epithelium. They induce hypertrophy, ongoing proliferation, apoptosis and squamous metaplasia. The endometrium gets infiltrated with eosinophils and neutrophils. These effects suggest an unopposed action of estrogen. However ultrastructurally some signs for a progesterone agonistic action - the induction of large secretory granules and the prevention of an estrogenic over-stimulation - are found.