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      • Record: found
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      Efficacy, safety and recurrence of new progestins and selective progesterone receptor modulator for the treatment of endometriosis: a comparison study in mice

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          Abstract

          Background

          Current medical treatments for endometriosis are very limited. Progestin and selective progesterone receptor modulators (SPRM) are developed but their efficacy, safety, mechanism and recurrence in endometriosis are not fully studied.

          Methods

          In order to compare therapeutic, side effects and therapeutic actions of Esmya, Duphaston and Dienogest in endometriosis. Experimental endometriosis was induced by either intraperitoneal or subcutaneous mouse endometrium transplantation. Lesion size, weight and histology at the end of intervention were compared. Expression of related markers in the endometriotic lesions were examined. Body, uterus and ovary weights, endometrial glands and thickness (ETI), and follicle count were measured. For recurrent study, lesion growth before and after intervention was monitored.

          Results

          After Esmya, Duphaston, Dienogest treatment, lesion size and weight were significantly decreased. Proliferation Pcna expression was significantly decreased in all groups, but proliferation cells were significantly decreased only in Duphaston group. Apoptosis Mapk1 expression and TUNEL-positive cells were significantly increased in Duphaston group. Adhesion Mmp2 and Itgavβ3 expression were significantly increased in Esmya group. Plau, Hif1α and Vegfa expression, peritoneal fluid PGE2 levels, and ERα and ERβ expression were not affected; while PR expression was significantly lower in all groups. Endometrial gland count in uterus was significantly increased in Dienogest group, ETI was significantly decreased in Duphaston group, and AFC were significantly increased in Esmya group. Upon treatment cessation, lesion growth rebound quickly in Dienogest and Duphaston groups, but slowly in Esmya group.

          Conclusion

          Esmya, Duphaston and Dienogest are effective anti-endometriosis drugs targeting proliferation, apoptosis and adhesion. Esmya, Duphaston and Dienogest are all well tolerable, although endometrial glandular hyperplasia was found in Dienogest, endometrial atrophy in Duphaston, follicle accumulation in Esmya.

          Electronic supplementary material

          The online version of this article (10.1186/s12958-018-0347-9) contains supplementary material, which is available to authorized users.

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          Most cited references64

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          PCNA, the maestro of the replication fork.

          George-Lucian Moldovan, Boris Pfander, Stefan Jentsch (2007)
          Inheritance requires genome duplication, reproduction of chromatin and its epigenetic information, mechanisms to ensure genome integrity, and faithful transmission of the information to progeny. Proliferating cell nuclear antigen (PCNA)-a cofactor of DNA polymerases that encircles DNA-orchestrates several of these functions by recruiting crucial players to the replication fork. Remarkably, many factors that are involved in replication-linked processes interact with a particular face of PCNA and through the same interaction domain, indicating that these interactions do not occur simultaneously during replication. Switching of PCNA partners may be triggered by affinity-driven competition, phosphorylation, proteolysis, and modification of PCNA by ubiquitin and SUMO.
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            Mitogen-activated protein kinases in apoptosis regulation.

            Teiji Wada, Josef M. Penninger (2004)
            Cells are continuously exposed to a variety of environmental stresses and have to decide 'to be or not to be' depending on the types and strength of stress. Among the many signaling pathways that respond to stress, mitogen-activated protein kinase (MAPK) family members are crucial for the maintenance of cells. Three subfamilies of MAPKs have been identified: extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinases (JNKs), and p38-MAPKs. It has been originally shown that ERKs are important for cell survival, whereas JNKs and p38-MAPKs were deemed stress responsive and thus involved in apoptosis. However, the regulation of apoptosis by MAPKs is more complex than initially thought and often controversial. In this review, we discuss MAPKs in apoptosis regulation with attention to mouse genetic models and critically point out the multiple roles of MAPKs.
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              Recurrence of endometriosis and its control.

              S.-W. Guo (2009)
              BACKGROUND Although surgery is currently the treatment of choice for managing endometriosis, recurrence poses a formidable challenge. To delay or to eliminate the recurrence is presently an unmet medical need in the management of endometriosis. To this end, proposals to investigate patterns of recurrence, to develop biomarkers for recurrence and to carry out biomarker-based intervention have been made. METHODS Publications pertaining to the recurrence of endometriosis and its related yet unaddressed issues were identified through MEDLINE. The reported recurrence rates, risk factors for recurrence, the effects of post-operative medication and causes of recurrence were reviewed and synthesized. In addition, several poorly explored issues such as time hazard function and mechanisms of recurrence were reviewed. Approaches to the development of biomarkers for recurrence and future intervention are discussed. RESULTS The reported recurrence rate was high, estimated as 21.5% at 2 years and 40-50% at 5 years. Few risk factors for recurrence have been consistently identified, and the evidence on the efficacy of the post-operative use of medication was scanty. The investigation on the patterns of recurrence may provide us with new insight into the possible mechanisms of recurrence and its control. The attempt to identify biomarkers for recurrence has started only very recently. CONCLUSIONS Much research is needed to better understand the patterns of recurrence and risk factors, and to develop biomarkers. One top priority is to develop biomarkers for recurrence, which may provide much needed clues to the possible mechanisms underlying recurrence and would allow the identification of patients with high recurrence risk, and permit for targeted intervention.
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                Author and article information

                Contributors
                Chi Chiu Wang: ccwang@cuhk.edu.hk
                Journal
                Journal ID (nlm-ta): Reprod Biol Endocrinol
                Journal ID (iso-abbrev): Reprod. Biol. Endocrinol
                Title: Reproductive Biology and Endocrinology : RB&E
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1477-7827
                Publication date (Electronic): 3 April 2018
                Publication date PMC-release: 3 April 2018
                Publication date Collection: 2018
                Volume: 16
                Electronic Location Identifier: 32
                Affiliations
                [1 ]ISNI 0000 0004 1937 0482, GRID grid.10784.3a, Department of Obstetrics and Gynaecology, , The Chinese University of Hong Kong, ; c/o 1st Floor, Special Block E, Prince of Wales Hospital, Shatin, Hong Kong
                [2 ]ISNI 0000 0004 1937 0482, GRID grid.10784.3a, Reproduction and Development Laboratory, Li Ka Shing Institute of Health Sciences, , The Chinese University of Hong Kong, ; Shatin, Hong Kong
                [3 ]ISNI 0000 0004 1937 0482, GRID grid.10784.3a, School of Biomedical Sciences, , The Chinese University of Hong Kong, ; Shatin, Hong Kong
                Article
                Publisher ID: 347
                DOI: 10.1186/s12958-018-0347-9
                PMC ID: 5883298
                PubMed ID: 29615065
                SO-VID: f788514d-2f85-4c42-b7c8-8705cf1631df
                Copyright © © The Author(s). 2018
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 6 January 2018
                Date accepted : 13 March 2018
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2018

                ScienceOpen disciplines: Human biology
                Keywords: progestin,selective progesterone receptor modulator,endometrium
                Data availability:
                ScienceOpen disciplines: Human biology
                Keywords: progestin, selective progesterone receptor modulator, endometrium

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