Progesterone receptor modulators for endometriosis

Fu, Jing; Song, Hao; Zhou, Min; Zhu, Huili; Wang, Yuhe; Chen, Hengxi; Huang, Wei

doi:10.1002/14651858.cd009881.pub2

Cited by 38 publications

(27 citation statements)

References 32 publications

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“…Other medications of interest are the levonorgestrel-releasing intrauterine system and mifepristone, which were not used in the studies included in this review. Nonetheless, their clinical utility may be explored as these have been shown to be effective in suppressing the menstrual cycles and relieving pain associated with endometriosis [98,99].…”

Section: Discussionmentioning

confidence: 99%

Clinical Presentation and Management of Endometriosis-Related Hemorrhagic Ascites: A Case Report and Systematic Review of the Literature

Chan-Tiopianco¹,

Chao²,

Ching³

et al. 2021

Cureus

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Section: Discussionmentioning

confidence: 99%

Clinical Presentation and Management of Endometriosis-Related Hemorrhagic Ascites: A Case Report and Systematic Review of the Literature

Chan-Tiopianco¹,

Chao²,

Ching³

et al. 2021

Cureus

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“…Mifepristone also reduces lesion size in animal models and patients (Kettel et al, 1996;Mei et al, 2010). In parallel with these findings, a systematic review of 10 randomized controlled trials assessing the efficacy of SRPMs for relief of endometriosis-associated pain concluded that mifepristone relieves dysmenorrhea and dyspareunia, with insufficient evidence of efficacy and safety of other SPRMs (Fu et al, 2017). SPRMs may be a promising new type of medication for clinical use, but their long-term efficacy remains to be proven (Whitaker et al, 2014).…”

Section: Novel Therapeutic Approaches Targeting Steroid Receptorsmentioning

confidence: 99%

Endometriosis and nuclear receptors

Yilmaz

Bulun

2019

Human Reproduction Update

169

128

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BACKGROUND Endometriosis is recognized as a steroid-dependent disorder; however, the precise roles of nuclear receptors (NRs) in steroid responsiveness and other signaling pathways are not well understood. OBJECTIVE AND RATIONALE Over the past several years, a number of paradigm-shifting breakthroughs have occurred in the area of NRs in endometriosis. We review and clarify new information regarding the mechanisms responsible for: (i) excessive estrogen biosynthesis, (ii) estrogen-dependent inflammation, (iii) defective differentiation due to progesterone resistance and (iv) enhanced survival due to deficient retinoid production and action in endometriosis. We emphasize the roles of the relevant NRs critical for these pathological processes in endometriosis. SEARCH METHODS We conducted a comprehensive search using PubMed for human, animal and cellular studies published until 2018 in the following areas: endometriosis; the steroid and orphan NRs, estrogen receptors alpha (ESR1) and beta (ESR2), progesterone receptor (PGR), steroidogenic factor-1 (NR5A1) and chicken ovalbumin upstream promoter-transcription factor II (NR2F2); and retinoids. OUTCOMES Four distinct abnormalities in the intracavitary endometrium and extra-uterine endometriotic tissue underlie endometriosis progression: dysregulated differentiation of endometrial mesenchymal cells, abnormal epigenetic marks, inflammation activated by excess estrogen and the development of progesterone resistance. Endometriotic stromal cells compose the bulk of the lesions and demonstrate widespread epigenetic abnormalities. Endometriotic stromal cells also display a wide range of abnormal NR expression. The orphan NRs NR5A1 and NR2F2 compete to regulate steroid-synthesizing genes in endometriotic stromal cells; NR5A1 dominance gives rise to excessive estrogen formation. Endometriotic stromal cells show an abnormally low ESR1:ESR2 ratio due to excessive levels of ESR2, which mediates an estrogen-driven inflammatory process and prostaglandin formation. These cells are also deficient in PGR, leading to progesterone resistance and defective retinoid synthesis. The pattern of NR expression, involving low ESR1 and PGR and high ESR2, is reminiscent of uterine leiomyoma stem cells. This led us to speculate that endometriotic stromal cells may display stem cell characteristics found in other uterine tissues. The biologic consequences of these abnormalities in endometriotic tissue include intense inflammation, defective differentiation and enhanced survival. WIDER IMPLICATIONS Steroid- and other NR-related abnormalities exert genome-wide biologic effects via interaction with defective epigenetic programming and enhance inflammation in endometriotic stromal cells. New synthetic ligands, targeting PGR, retinoic acid receptors and ESR2, may offer novel treatment options.

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“…Amenorrhoea is a common association and is classed as a 'side effect', although, lack of menstruation may be clearly beneficial in women with endometriosis-associated HMB. Doses <2.5 mg/day are less likely to be effective; however, based on the available evidence, clear conclusions on dosage cannot be made (Fu et al 2017).…”

Section: Mifepristone and Endometriosismentioning

confidence: 99%

90 YEARS OF PROGESTERONE: Selective progesterone receptor modulators in gynaecological therapies

Critchley

Chodankar

2020

Journal of Molecular Endocrinology

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Abnormal uterine bleeding (AUB) is a chronic, debilitating and common condition affecting one in four women of reproductive age. Current treatments (conservative, medical and surgical) may be unsuitable, poorly tolerated or may result in loss of fertility. Selective progesterone receptor modulators (SPRMs) influence progesterone-regulated pathways, a hormone critical to female reproductive health and disease; therefore, SPRMs hold great potential in fulfilling an unmet need in managing gynaecological disorders. SPRMs in current clinical use include RU486 (mifepristone), which is licensed for pregnancy interruption, and CDB-2914 (ulipristal acetate), licensed for managing AUB in women with leiomyomas and in a higher dose as an emergency contraceptive. In this article, we explore the clinical journey of SPRMs and the need for further interrogation of this class of drugs with the ultimate goal of improving women’s quality of life.

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Progesterone receptor modulators for endometriosis

Abstract: * The basis f or the assumed risk is the m ean control group risk across studies. The corresponding risk (and its 95% conf idence interval) is based on the assum ed risk in the com parison group and the relative effect of the intervention (and its 95% CI

Cited by 38 publications

References 32 publications

Clinical Presentation and Management of Endometriosis-Related Hemorrhagic Ascites: A Case Report and Systematic Review of the Literature

Clinical Presentation and Management of Endometriosis-Related Hemorrhagic Ascites: A Case Report and Systematic Review of the Literature

Endometriosis and nuclear receptors

90 YEARS OF PROGESTERONE: Selective progesterone receptor modulators in gynaecological therapies

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