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Reduced progesterone action during endometrial maturation: A potential risk factor for the development of endometriosis
Open accessAbstract
Objective To discuss the role that reduced endometrial responsiveness to progesterone (P) might play in the pathophysiology of endometriosis. Design A review of experimental evidence regarding the failure of P to regulate the expression of matrix metalloproteinases (MMPs) in the endometrium of patients with endometriosis. Conclusion(s) Progesterone and locally produced differentiation factors act cooperatively to reduce MMP expression by maternal endometrial cells within the pro-inflammatory micro-environment of early pregnancy. Our in vitro studies with normal human endometrium demonstrate that prior P exposure not only down-regulates MMP expression, but also limits the ability of locally produced proinflammatory cytokines to stimulate expression of these enzymes. In contrast, endometrial tissues from women with endometriosis demonstrate an altered response to P, allowing a continuous expression of MMPs throughout the secretory phase. Although the factors that influence the loss of P sensitivity in the endometrium of patients with endometriosis have not yet been defined, alterations in cell-cell communication seem to contribute to dysregulated MMP expression. Specifically, proinflammatory cytokines produced by epithelial cells oppose stromal cell responses to P, inhibiting production of key differentiation factors necessary for cell-specific MMP regulation. The resulting loss in normal MMP regulation enhances the invasive capacity of endometrial tissue, promoting ectopic establishment in an experimental model.
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“A reduction in progesterone action in endometrium, 'progesterone resistance', of women with endometriosis (Osteen et al., 2005; Table V) may play a key role in development of endometriosis and possibly with associated pain; use of progestagens may reverse these effects.”
From Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications (2011) · cites this paper as Osteen et al., 2005
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“Osteen et al. (2005) demonstrated that eutopic endometrium of women with endometriosis has reduced progesterone action during maturation or 'progesterone resistance', that, in turn, may enhance development of endometriosis.”
From Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications (2011) · cites this paper as Osteen et al., 2005
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Metadata
- Authors
- Osteen, K. G., Bruner-Tran, K. L., & Eisenberg, E.
- Affiliations
- Vanderbilt University (US)
- Corresponding author
- Osteen, Kevin G.
- Venue
- Fertility and Sterility
- Publisher
- Elsevier BV
- Published
- 2005-03
- Volume
- 83
- Issue
- 3
- Pages
- 529-537
- ISSN
- 0015-0282 (ISSN-L)
- OpenAlex
- W1966049599
- Cited by
- 122
- References
- 63
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 2 · 2022: 7 · 2021: 8 · 2020: 2 · 2019: 6 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 6 · 2014: 5 · 2013: 4 · 2012: 11
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Fertility and Sterility (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Environmental Health Sciences (R21ES12298-01, R21ES012298)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (5K12HD43483, U54HD037321, U54 HD37321, K12HD043483)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Health Sciences › Medicine › Obstetrics and Gynecology › Ectopic Pregnancy Diagnosis and Management
- Keywords
- endometriosis, progesterone, endometrial maturation, matrix metalloproteinases, endometrial receptivity, inflammatory cytokines, endometrial invasion, luteal phase, intercellular communication, ectopic endometrium
- MeSH terms
- Endometriosis, Endometrium, Female, Humans, Pregnancy, Progesterone, Risk Factors
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