The effects of the selective progesterone receptor modulator asoprisnil on the morphology of uterine tissues after 3 months treatment in patients with symptomatic uterine leiomyomata

Abstract

Asoprisnil induces unique morphological changes and is associated with low levels of glandular and stromal proliferation in endometrium, and in leiomyomata. These changes are likely to contribute to the amenorrhoea experienced after exposure to the medication.

The spectrum of endometrial pathology induced by progesterone receptor modulators

“…Similar vessels have been described for the PRM asoprisnil. 7 The stromal changes seen were unique and differed from those in endometrial polyps. In bland septated cysts, stroma appeared almost fibrous, whereas in other examples nuclei appeared plump with mitotic figures.…”

“…Cyst formation and mixed progestin agonist/antagonist effects have been described for the PRMs asoprisnil 7 and VA2914. 18 This 'non-physiological secretory effect' had an appearance that differed by dose, including decreasing mitotic figure count as the dose of the agent increased.…”

“…The pharmacological effects of PRMs are, however, not purely antagonistic, nor is their effect restricted to the progesterone receptor itself. Some PRMs exert anti-estrogenic effects, either through partial progesterone receptor agonist activity, 6,7 or, exert these effects independently of the progesterone receptor itself, that is by upregulation of the androgen receptor response. 8,9 These PRM effects are evident as dose-dependent suppression of estrogen-induced mitotic activity, [10][11][12] and appearance of glandular secretory changes.…”

“…8,9 These PRM effects are evident as dose-dependent suppression of estrogen-induced mitotic activity, [10][11][12] and appearance of glandular secretory changes. 7 Assessment of PRM induced changes in the endometrium by pathologists is not only a prerequisite step to determine suitability for widespread clinical use, but also indicates how community pathologists are likely to respond to endometrial biopsies from women on these agents. Pathologists simply do not have a historical or established community experience with long-term PRM administration to use as a basis for interpretation.…”

“…Access to material is generally confined to individuals involved in ongoing clinical trials, members of the parent pharmaceutical companies, a few researchers, and regulatory agencies. Now that the histological features referable to PRM administration are starting to emerge, 7,[12][13][14][15] there are unanswered questions of how they relate, if at all, to known diagnostic entities such as endometrial hyperplasia.…”