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      Selective progesterone receptor modulators (SPRMs): progesterone receptor action, mode of action on the endometrium and treatment options in gynecological therapies

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          ABSTRACT

          Introduction: The progesterone receptor plays an essential role in uterine physiology and reproduction. Selective progesterone receptor modulators (SPRMs) have emerged as a valuable treatment option for hormone dependent conditions like uterine fibroids, which have a major impact on women’s quality of life. SPRMs offer potential for longer term medical treatment and thereby patients may avoid surgical intervention.

          Areas covered: The authors have reviewed the functional role of the progesterone receptor and its isoforms and their molecular mechanisms of action via genomic and non-genomic pathways. The current knowledge of the interaction of the PR and different SPRMs tested in clinical trials has been reviewed. The authors focused on pharmacological effects of selected SPRMs on the endometrium, their anti-proliferative action, and their suppression of bleeding. Potential underlying molecular mechanisms and the specific histological changes in the endometrium induced by SPRMs (PAEC; Progesterone receptor modulator Associated Endometrial Changes) have been discussed. The clinical potential of this compound class including its impact on quality of life has been covered.

          Expert Opinion: Clinical studies indicate SPRMs hold promise for treatment of benign gynecological complaints (fibroids, heavy menstrual bleeding; HMB). There however remains a knowledge gap concerning mechanism of action.

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          Most cited references 110

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          The nuclear receptor superfamily: the second decade.

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            Epidemiology of endometriosis.

             B Eskenazi,  M Warner (1997)
            This article summarizes present knowledge about the epidemiology of endometriosis. Surprisingly, little is known about the prevalence or risk factors of endometriosis, given the medical care and employment costs. Knowledge about the epidemiology of endometriosis is hampered by the inability to diagnose this disease in the general population. Based on a single cohort study, it is estimated that there is a 10% prevalence of endometriosis in the general population. Age is the only sociodemographic characteristic for which a consistent positive relationship has been observed. In general, the risk of endometriosis appears to increase for reproductive health factors that may relate to increased exposure to menstruation (i.e., shorter cycle length, longer duration of flow, or reduced parity). The risk appears to decrease for personal habits that may relate to decreased estrogen levels (i.e., smoking, exercise).
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              Steroid hormone receptors: many actors in search of a plot.

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                Author and article information

                Journal
                Expert Opin Ther Targets
                Expert Opin. Ther. Targets
                IETT
                iett20
                Expert Opinion on Therapeutic Targets
                Taylor & Francis
                1472-8222
                1744-7631
                1 September 2016
                14 May 2016
                : 20
                : 9
                : 1045-1054
                Affiliations
                [ a ]Bayer HealthCare, Drug Discovery, TRG Gynecological Therapies , Berlin, Germany
                [ b ]MRC Centre for Inflammation Research, The University of Edinburgh , Edinburgh, UK
                [ c ]MRC Centre for Reproductive Health, The University of Edinburgh , Edinburgh, UK
                Author notes
                CONTACT Hilary O.D. Critchley hilary.critchley@ 123456ed.ac.uk MRC Centre for Reproductive Health, The University of Edinburgh , Edinburgh, Scotland, UK
                Article
                1180368
                10.1080/14728222.2016.1180368
                4989858
                27138351
                © 2016 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Page count
                Figures: 3, Tables: 1, References: 111, Pages: 10
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