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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

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
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
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.
methods, activity, receptors, leiomyoma, middle aged, drug therapy, drug effects, pathology, research, uterus, oximes, exposure, placebos, estrenes, administration & dosage, adverse effects, humans, endometrium, myometrium, progesterone, uterine neoplasms, female, adult
1696-1704
Williams, A.R.W.
973ff46f-46f1-4d7c-b27d-0f53221e4c44
Critchley, H.O.D.
4b7fb4e8-0545-468a-88e0-ee3aa8efb81b
Osei, J.
431c4d00-068b-4060-bf74-e0c60a8fa260
Ingamells, S.
89e5440e-af33-4070-9570-4170f6f0019b
Cameron, I.T.
f7595539-efa6-4687-b161-e1e93ff710f2
Han, C.
fd5b11fe-fccf-4e00-ad20-9d1a4e528f1a
Chwalisz, K.
49b9ee58-ab3a-441c-92d5-22e4320d02aa
Williams, A.R.W.
973ff46f-46f1-4d7c-b27d-0f53221e4c44
Critchley, H.O.D.
4b7fb4e8-0545-468a-88e0-ee3aa8efb81b
Osei, J.
431c4d00-068b-4060-bf74-e0c60a8fa260
Ingamells, S.
89e5440e-af33-4070-9570-4170f6f0019b
Cameron, I.T.
f7595539-efa6-4687-b161-e1e93ff710f2
Han, C.
fd5b11fe-fccf-4e00-ad20-9d1a4e528f1a
Chwalisz, K.
49b9ee58-ab3a-441c-92d5-22e4320d02aa

Williams, A.R.W., Critchley, H.O.D., Osei, J., Ingamells, S., Cameron, I.T., Han, C. and Chwalisz, K. (2007) 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. Human Reproduction, 22 (6), 1696-1704. (doi:10.1093/humrep/dem026).

Record type: Article

Abstract

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.

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Published date: June 2007
Keywords: methods, activity, receptors, leiomyoma, middle aged, drug therapy, drug effects, pathology, research, uterus, oximes, exposure, placebos, estrenes, administration & dosage, adverse effects, humans, endometrium, myometrium, progesterone, uterine neoplasms, female, adult

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Local EPrints ID: 61610
URI: http://eprints.soton.ac.uk/id/eprint/61610
PURE UUID: a96bd543-96c5-4801-9795-72b3bba1a7a8
ORCID for I.T. Cameron: ORCID iD orcid.org/0000-0002-4875-267X

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Date deposited: 11 Sep 2008
Last modified: 16 Mar 2024 03:00

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Contributors

Author: A.R.W. Williams
Author: H.O.D. Critchley
Author: J. Osei
Author: S. Ingamells
Author: I.T. Cameron ORCID iD
Author: C. Han
Author: K. Chwalisz

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