Anton Sommar , Pinar Yalcin Bahat , Ipek Yildiz Özaydin , Marie Bixo , Torbjörn Bäckström , Engin Oral , Sahruh Turkmen
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Pain symptom severity was measured using VAS and EHP30.</div></div><div><h3>Results</h3><div>Women with endometriosis had a higher density of endometrial nerve fibers than healthy controls (median [range]: 2.0 [2.0–4.0] vs. 1.0 [0.0–1.0] fibers/mm<sup>2</sup>, P < 0.001). This increased density was associated with more severe pain (β = 0.130 [95 % CI: 0.019, 0.240], P = 0.02). Women with endometriosis, regardless of hormone treatment, had a higher density of endometrial nerve fibers (3.0 [2.0–4.0] and 2.0 [1.0–4.0] fibers/mm<sup>2</sup>, respectively) compared with healthy controls (1.0 [0.0-u1.0] fibers/mm<sup>2</sup>, both P < 0.001). The density was not significantly different between those receiving and not receiving hormone treatment. The allopregnanolone/progesterone ratio was greater in women with endometriosis not receiving hormone treatment (0.002 [0.001–0.004]) than in healthy controls (0.001 [0.000–0.005]) and women receiving hormone treatment (0.001 [0.000–0.006], P = 0.02 and 0.001, respectively). A greater allopregnanolone/progesterone ratio was associated with more severe pain (β = 20.662 [95 % CI: 0.202, 41.121], P = 0.048), but hormone levels (estrogen, progesterone, and allopregnanolone) were not associated with endometrial nerve fiber density.</div></div><div><h3>Conclusion</h3><div>Women with endometriosis have a higher nerve fiber density in the endometrium, linked to more severe pain, regardless of hormone treatment. Increased progesterone metabolism to allopregnanolone may be a target for managing endometriosis pain.</div></div>","PeriodicalId":11975,"journal":{"name":"European journal of obstetrics, gynecology, and reproductive biology","volume":"310 ","pages":"Article 113950"},"PeriodicalIF":2.1000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Influence of endometrial nerve fibers and hormones on pain in women with endometriosis\",\"authors\":\"Anton Sommar , Pinar Yalcin Bahat , Ipek Yildiz Özaydin , Marie Bixo , Torbjörn Bäckström , Engin Oral , Sahruh Turkmen\",\"doi\":\"10.1016/j.ejogrb.2025.113950\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><div>The mechanisms behind endometriosis-related pain are not yet fully understood. To determine if there is a difference in the density of endometrial nerve fibers between women with endometriosis and healthy controls, and to explore how the density of these nerve fibers and hormone levels correlate with the severity of symptoms experienced by the women.</div></div><div><h3>Study Design</h3><div>In this case-control study, 76 women with endometriosis and 24 healthy controls were included. The patient group was divided into two subgroups: those with and without hormonal treatments. Endometrial biopsies were taken and stained to detect PGP 9.5, a nerve fiber marker. Blood samples were collected for hormone analysis. Pain symptom severity was measured using VAS and EHP30.</div></div><div><h3>Results</h3><div>Women with endometriosis had a higher density of endometrial nerve fibers than healthy controls (median [range]: 2.0 [2.0–4.0] vs. 1.0 [0.0–1.0] fibers/mm<sup>2</sup>, P < 0.001). This increased density was associated with more severe pain (β = 0.130 [95 % CI: 0.019, 0.240], P = 0.02). Women with endometriosis, regardless of hormone treatment, had a higher density of endometrial nerve fibers (3.0 [2.0–4.0] and 2.0 [1.0–4.0] fibers/mm<sup>2</sup>, respectively) compared with healthy controls (1.0 [0.0-u1.0] fibers/mm<sup>2</sup>, both P < 0.001). The density was not significantly different between those receiving and not receiving hormone treatment. The allopregnanolone/progesterone ratio was greater in women with endometriosis not receiving hormone treatment (0.002 [0.001–0.004]) than in healthy controls (0.001 [0.000–0.005]) and women receiving hormone treatment (0.001 [0.000–0.006], P = 0.02 and 0.001, respectively). A greater allopregnanolone/progesterone ratio was associated with more severe pain (β = 20.662 [95 % CI: 0.202, 41.121], P = 0.048), but hormone levels (estrogen, progesterone, and allopregnanolone) were not associated with endometrial nerve fiber density.</div></div><div><h3>Conclusion</h3><div>Women with endometriosis have a higher nerve fiber density in the endometrium, linked to more severe pain, regardless of hormone treatment. 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引用次数: 0
摘要
目的子宫内膜异位症相关疼痛的机制尚不完全清楚。确定子宫内膜异位症女性和健康女性的子宫内膜神经纤维密度是否存在差异,并探讨这些神经纤维密度和激素水平与女性所经历的症状严重程度之间的关系。在这项病例对照研究中,包括76名子宫内膜异位症妇女和24名健康对照者。患者组被分为两个亚组:接受激素治疗的和未接受激素治疗的。取子宫内膜活检并染色检测PGP 9.5(一种神经纤维标志物)。采集血液样本进行激素分析。采用VAS和EHP30测量疼痛症状严重程度。结果子宫内膜异位症患者子宫内膜神经纤维密度高于健康对照组(中位数[范围]:2.0 [2.0 - 4.0]vs. 1.0[0.0-1.0]纤维/mm2, P <;0.001)。这种密度增加与更严重的疼痛相关(β = 0.130 [95% CI: 0.019, 0.240], P = 0.02)。子宫内膜异位症的女性,无论激素治疗,其子宫内膜神经纤维密度(分别为3.0[2.0 - 4.0]和2.0[1.0 - 4.0]纤维/mm2)高于健康对照组(1.0 [0.0-u1.0]纤维/mm2, P <;0.001)。接受和未接受激素治疗组间的密度无显著差异。未接受激素治疗的子宫内膜异位症患者的异孕酮/孕酮比值(0.002[0.001 - 0.004])高于健康对照组(0.001[0.000-0.005])和接受激素治疗的女性(0.001 [0.000-0.006],P分别= 0.02和0.001)。异孕酮/孕酮比值越大,疼痛越严重(β = 20.662 [95% CI: 0.202, 41.121], P = 0.048),但激素水平(雌激素、孕酮和异孕酮)与子宫内膜神经纤维密度无关。结论子宫内膜异位症患者的子宫内膜神经纤维密度较高,与更严重的疼痛有关,无论激素治疗如何。增加孕酮对异孕酮的代谢可能是治疗子宫内膜异位症疼痛的一个目标。
Influence of endometrial nerve fibers and hormones on pain in women with endometriosis
Objective
The mechanisms behind endometriosis-related pain are not yet fully understood. To determine if there is a difference in the density of endometrial nerve fibers between women with endometriosis and healthy controls, and to explore how the density of these nerve fibers and hormone levels correlate with the severity of symptoms experienced by the women.
Study Design
In this case-control study, 76 women with endometriosis and 24 healthy controls were included. The patient group was divided into two subgroups: those with and without hormonal treatments. Endometrial biopsies were taken and stained to detect PGP 9.5, a nerve fiber marker. Blood samples were collected for hormone analysis. Pain symptom severity was measured using VAS and EHP30.
Results
Women with endometriosis had a higher density of endometrial nerve fibers than healthy controls (median [range]: 2.0 [2.0–4.0] vs. 1.0 [0.0–1.0] fibers/mm2, P < 0.001). This increased density was associated with more severe pain (β = 0.130 [95 % CI: 0.019, 0.240], P = 0.02). Women with endometriosis, regardless of hormone treatment, had a higher density of endometrial nerve fibers (3.0 [2.0–4.0] and 2.0 [1.0–4.0] fibers/mm2, respectively) compared with healthy controls (1.0 [0.0-u1.0] fibers/mm2, both P < 0.001). The density was not significantly different between those receiving and not receiving hormone treatment. The allopregnanolone/progesterone ratio was greater in women with endometriosis not receiving hormone treatment (0.002 [0.001–0.004]) than in healthy controls (0.001 [0.000–0.005]) and women receiving hormone treatment (0.001 [0.000–0.006], P = 0.02 and 0.001, respectively). A greater allopregnanolone/progesterone ratio was associated with more severe pain (β = 20.662 [95 % CI: 0.202, 41.121], P = 0.048), but hormone levels (estrogen, progesterone, and allopregnanolone) were not associated with endometrial nerve fiber density.
Conclusion
Women with endometriosis have a higher nerve fiber density in the endometrium, linked to more severe pain, regardless of hormone treatment. Increased progesterone metabolism to allopregnanolone may be a target for managing endometriosis pain.
期刊介绍:
The European Journal of Obstetrics & Gynecology and Reproductive Biology is the leading general clinical journal covering the continent. It publishes peer reviewed original research articles, as well as a wide range of news, book reviews, biographical, historical and educational articles and a lively correspondence section. Fields covered include obstetrics, prenatal diagnosis, maternal-fetal medicine, perinatology, general gynecology, gynecologic oncology, uro-gynecology, reproductive medicine, infertility, reproductive endocrinology, sexual medicine and reproductive ethics. The European Journal of Obstetrics & Gynecology and Reproductive Biology provides a forum for scientific and clinical professional communication in obstetrics and gynecology throughout Europe and the world.