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Eutopic endometrial cells from women with endometriosis fail to downregulate genes needed for decidualization, such as those involved in cell cycle regulation, leading to unbridled proliferation. Several causes of progesterone resistance in the endometrium have been postulated, including congenital \u201cpreconditioning\u201d, whereby the in utero environment renders infants susceptible to neonatal uterine bleeding and endometriosis. Progesterone action is crucial to decreasing inflammation in the endometrium, and deviant progesterone signaling results in a proinflammatory phenotype. Conversely, chronic inflammation can induce a progesterone\u2010resistant state. Repetitive retrograde endometrial shedding begets chronic peritoneal inflammation, which further exacerbates progesterone resistance. Genetic causes of progesterone resistance include progesterone receptor gene polymorphisms, altered micro<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> expression, and epigenetic modifications to progesterone receptors and their targets. Environmental toxins such as dioxin play a possible role in the genesis of endometriosis by permitting an inflammatory milieu. A consequence of impaired progesterone action is that hormonal therapy is rendered ineffective for a subset of women with endometriosis. Synthetic progestins, such as dienogest, may overcome this phenomenon by increasing progesterone receptor expression and decreasing proinflammatory cytokines. Other modalities include high dose depot formulations of progestins, medicated intrauterine devices and the likely advent of oral Gn<jats:styled-content style=\"fixed-case\">RH<\/jats:styled-content> antagonists. Unearthing root causes of progesterone inaction in endometriosis will aid in the development of novel therapeutics geared toward prevention and treatment.<\/jats:p>","DOI":"10.1111\/aogs.13156","type":"journal-article","created":{"date-parts":[[2017,4,19]],"date-time":"2017-04-19T23:02:48Z","timestamp":1492642968000},"page":"623-632","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":298,"title":["Progesterone resistance in endometriosis: origins, consequences and interventions"],"prefix":"10.1111","volume":"96","author":[{"given":"Bansari G.","family":"Patel","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Wake Forest School of Medicine Winston\u2010Salem NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5115-1445","authenticated-orcid":false,"given":"Martin","family":"Rudnicki","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Odense University Hospital Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Wake Forest School of Medicine Winston\u2010Salem NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimin","family":"Shu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Wake Forest School of Medicine Winston\u2010Salem NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert N.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Wake Forest School of Medicine Winston\u2010Salem NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,5,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1152\/ajplegacy.1929.88.2.326","article-title":"Physiology of the corpus luteum. 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