Hum. Reprod. Advance Access originally published online on March 5, 2007
Human Reproduction 2007 22(6):1696-1704; doi:10.1093/humrep/dem026
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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
1 Department of Pathology, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh, Scotland, UK 2 Centre for Reproductive Biology, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, Scotland, UK 3 DOHaD (Developmental Origins of Health and Disease) Division, University of Southampton, Princess Anne Hospital, Southampton, UK 4 TAP Pharmaceutical Products Inc., Lake Forest, Illinois, IL, USA
5 To whom correspondence should be addressed at: Department of Pathology, University of Edinburgh, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh EH16 4SA, Scotland, UK. Tel.: +44 131 242 7120; E-mail: a.williams{at}ed.ac.uk
BACKGROUND: Asoprisnil is a selective progesterone receptor modulator with mixed progesterone agonist/antagonist activity which controls uterine bleeding via an endometrial effect. This study examined full-thickness endometrial, leiomyoma and myometrial morphology in hysterectomy specimens from patients with uterine leiomyomata, after treatment with asoprisnil for 3 months.
METHODS: In this double-blind, randomized, placebo-controlled study, 33 subjects with uterine leiomyomata were randomized to receive asoprisnil 10, 25 mg or placebo for an average of 95 days prior to hysterectomy. Samples of endometrium, myometrium and leiomyoma tissue were subjected to systematic morphological assessment with quantification of mitotic activity.
RESULTS: In patients treated with 10 or 25 mg asoprisnil, a unique pattern called ‘non-physiologic secretory effect’ was evident in endometrium, recognizable through partially developed secretory glandular appearances and stromal changes. Endometrial thickness was decreased, and there were low levels of mitotic activity in endometrial glands and stroma. Unusual thick-walled muscular arterioles and prominent aggregations of thin-walled vessels were present in endometrial stroma, but not in myometrium or non-endometrial vascular beds. Mitotic activity was decreased in leiomyomata.
CONCLUSIONS: 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.
Key words: asoprisnil/cell-proliferation/endometrium/histopathology/progesterone receptor
Submitted on July 3, 2006; resubmitted on November 14, 2006; accepted on December 27, 2006.
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