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Progestins are currently the most commonly used treatment for endometriosis because of their excellent therapeutic effects and limited side effects. However, progestins have been unsuccessful in some symptomatic patients. The inability of the endometrium to respond properly to progesterone is known as progesterone resistance. An increasing body of evidence suggests the loss of progesterone signaling and the existence of progesterone resistance in endometriosis. The mechanisms of progesterone resistance have received considerable scholarly attention in recent years. Abnormal PGR signaling, chronic inflammation, aberrant gene expression, epigenetic alterations, and environmental toxins are considered potential molecular causes of progesterone resistance in endometriosis. The general objective of this review was to summarize the evidence and mechanisms of progesterone resistance. A deeper understanding of how these mechanisms contribute to progesterone resistance may help develop a novel therapeutic regimen for women with endometriosis by reversing progesterone resistance.<\/jats:p>","DOI":"10.3390\/ijms24086992","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T03:49:29Z","timestamp":1681098569000},"page":"6992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":129,"title":["Progesterone Resistance in Endometriosis: Current Evidence and Putative Mechanisms"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4290-6934","authenticated-orcid":false,"given":"Ping","family":"Zhang","sequence":"first","affiliation":[{"name":"Medical Integration and Practice Center, Cheeloo College of Medicine, Shandong University, Jinan 250021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4023-084X","authenticated-orcid":false,"given":"Guoyun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Shandong Provincial Hospital, Shandong University, Jinan 250021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/s41574-019-0245-z","article-title":"Rethinking mechanisms, diagnosis and management of endometriosis","volume":"15","author":"Chapron","year":"2019","journal-title":"Nat. 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