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Prenatal Origins of Endometriosis Pathology and Pain: Reviewing the Evidence of a Role for Low Testosterone
Endometriosis is a polygenic, estrogen-dependent, inflammatory disorder of uncertain aetiology associated with pain, infertility and reduced quality of life. While the positive association between endometriosis and estrogen is established, a suite of recent studies has demonstrated an inverse associ...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9904225/ https://www.ncbi.nlm.nih.gov/pubmed/36762368 http://dx.doi.org/10.2147/JPR.S389166 |
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author | Crespi, Bernard J Evans, Susan F |
author_facet | Crespi, Bernard J Evans, Susan F |
author_sort | Crespi, Bernard J |
collection | PubMed |
description | Endometriosis is a polygenic, estrogen-dependent, inflammatory disorder of uncertain aetiology associated with pain, infertility and reduced quality of life. While the positive association between endometriosis and estrogen is established, a suite of recent studies has demonstrated an inverse association between the presence of endometriosis lesions and levels of testosterone both prenatally and postnatally. The following narrative review provides new insights into the roles of testosterone in the aetiology, diagnosis, and management of endometriosis and associated symptoms, especially pain. A relatively short anogenital distance (AGD) is indicative of lower levels of testosterone during fetal development. A shorter AGD has recently been correlated with both a higher risk of developing endometriosis in adult life, and with known correlates of endometriosis including earlier onset of reproductive cycling, lower ovarian follicle number, lower postnatal testosterone, and premature ovarian insufficiency. During adult life, lower levels of testosterone are positively associated with key comorbidities of endometriosis, including days per month of pelvic pain and increased pain sensitivity. Biochemically, lower levels of testosterone are associated with higher levels of pro-inflammatory IL-1β and lower levels of β-endorphin. In rodents, prenatal administration of testosterone to females reduces their pain sensitivity in adulthood. The emerging convergent links of endometriosis with low prenatal and postnatal testosterone provide evidence of a centrally mediated effect beginning in early prenatal development, and persisting through adult life, with notable effects on pain sensitivity. They generate a novel conceptual framework for understanding, studying and treating this disorder, whereby endometriosis is mediated by a combination of high estrogen in endometrial tissue with low systemic and ovarian testosterone. |
format | Online Article Text |
id | pubmed-9904225 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-99042252023-02-08 Prenatal Origins of Endometriosis Pathology and Pain: Reviewing the Evidence of a Role for Low Testosterone Crespi, Bernard J Evans, Susan F J Pain Res Perspectives Endometriosis is a polygenic, estrogen-dependent, inflammatory disorder of uncertain aetiology associated with pain, infertility and reduced quality of life. While the positive association between endometriosis and estrogen is established, a suite of recent studies has demonstrated an inverse association between the presence of endometriosis lesions and levels of testosterone both prenatally and postnatally. The following narrative review provides new insights into the roles of testosterone in the aetiology, diagnosis, and management of endometriosis and associated symptoms, especially pain. A relatively short anogenital distance (AGD) is indicative of lower levels of testosterone during fetal development. A shorter AGD has recently been correlated with both a higher risk of developing endometriosis in adult life, and with known correlates of endometriosis including earlier onset of reproductive cycling, lower ovarian follicle number, lower postnatal testosterone, and premature ovarian insufficiency. During adult life, lower levels of testosterone are positively associated with key comorbidities of endometriosis, including days per month of pelvic pain and increased pain sensitivity. Biochemically, lower levels of testosterone are associated with higher levels of pro-inflammatory IL-1β and lower levels of β-endorphin. In rodents, prenatal administration of testosterone to females reduces their pain sensitivity in adulthood. The emerging convergent links of endometriosis with low prenatal and postnatal testosterone provide evidence of a centrally mediated effect beginning in early prenatal development, and persisting through adult life, with notable effects on pain sensitivity. They generate a novel conceptual framework for understanding, studying and treating this disorder, whereby endometriosis is mediated by a combination of high estrogen in endometrial tissue with low systemic and ovarian testosterone. Dove 2023-02-03 /pmc/articles/PMC9904225/ /pubmed/36762368 http://dx.doi.org/10.2147/JPR.S389166 Text en © 2023 Crespi and Evans. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Perspectives Crespi, Bernard J Evans, Susan F Prenatal Origins of Endometriosis Pathology and Pain: Reviewing the Evidence of a Role for Low Testosterone |
title | Prenatal Origins of Endometriosis Pathology and Pain: Reviewing the Evidence of a Role for Low Testosterone |
title_full | Prenatal Origins of Endometriosis Pathology and Pain: Reviewing the Evidence of a Role for Low Testosterone |
title_fullStr | Prenatal Origins of Endometriosis Pathology and Pain: Reviewing the Evidence of a Role for Low Testosterone |
title_full_unstemmed | Prenatal Origins of Endometriosis Pathology and Pain: Reviewing the Evidence of a Role for Low Testosterone |
title_short | Prenatal Origins of Endometriosis Pathology and Pain: Reviewing the Evidence of a Role for Low Testosterone |
title_sort | prenatal origins of endometriosis pathology and pain: reviewing the evidence of a role for low testosterone |
topic | Perspectives |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9904225/ https://www.ncbi.nlm.nih.gov/pubmed/36762368 http://dx.doi.org/10.2147/JPR.S389166 |
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