{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T04:59:13Z","timestamp":1785387553123,"version":"3.55.0"},"reference-count":95,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education and Science"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>The pharmacological treatment of endometriosis using SPRMs requires improvement. The pure PR-agonist dienogest (DNG), a clinically established progestin, can serve as a reference compound for comparison. Its efficacy and safety have been well characterised in preclinical in vitro and in vivo studies, as well as in qualified pivotal clinical studies for the treatment of endometriosis. The pharmacodynamic profile of Dienogest (DNG) is compared with the experience of using the pure PR antagonist Vilaprisan and the mixed PR agonist\/antagonist Asoprisnil to treat endometriosis. Unfortunately, the clinical development of Vilaprisan was suspended due to long-term toxicology findings in animals that require further clarification. The clinical development of Asoprisnil, however, was discontinued due to concerns regarding SPRM-associated endometrial changes, although the interpretation of PAEC has been debated. Additionally, another SPRM, Ulipristal acetate, has been associated with rare but serious cases of liver injury. However, Vilaprisan is primarily supported by fibroid-related clinical development, whereas Asoprisnil has limited Phase II endometriosis evidence. Nevertheless, this new mesoprogestin, Asoprisnil, has shown signs of tissue-selective activity in limited clinical and preclinical studies. Continuing the strategy of using mixed PR agonists\/antagonists could inspire further drug development. The preclinical profile of the new mesoprogestin EC313 has been presented, showing a higher PR agonistic\/antagonistic quotient than Asoprisnil, with comparatively elevated anti-endometriotic activity. Furthermore, EC313 increases the progesterone receptor isoform B\/A ratio, but its clinical efficacy remains unproven as it is still in the early stages of development. Based on the preclinical data currently available, the next generation of mesoprogestins warrants further investigation for the treatment of endometriosis and related gynaecological disorders. This prompts consideration of whether there is potential to enhance the effectiveness of drug discovery strategies within this particular pharmacological class.<\/jats:p>","DOI":"10.3390\/ijms27156750","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T13:07:33Z","timestamp":1785244053000},"page":"6750","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring New Treatment Strategies for Endometriosis\u2014Narrative Review"],"prefix":"10.3390","volume":"27","author":[{"given":"Katarzyna","family":"B\u0142aszczak-\u015awi\u0105tkiewicz","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Social Academy of Sciences, Sienkiewicza 9, 90-113 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Oettel","sequence":"additional","affiliation":[{"name":"Independent Researcher, 90-113 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.3111\/13696998.2010.549532","article-title":"Surgical procedures and their cost estimates among women with nely diagnosed endometriosis: A US database study","volume":"14","author":"Fuldeore","year":"2011","journal-title":"J. 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