Influence of endometrial nerve fibers and hormones on pain in women with endometriosis
•Women with endometriosis had a higher density of PGP9.5-positive nerve fibers in the endometrium compared to healthy controls.•Higher nerve fiber density was linked to more severe pain (higher VAS score).•No association was found between hormone levels and nerve fiber density, and hormonal treatmen...
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| Vydáno v: | European journal of obstetrics & gynecology and reproductive biology Ročník 310; s. 113950 |
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| Médium: | Journal Article |
| Jazyk: | angličtina |
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Ireland
Elsevier B.V
01.06.2025
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| ISSN: | 0301-2115, 1872-7654, 1872-7654 |
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| Abstract | •Women with endometriosis had a higher density of PGP9.5-positive nerve fibers in the endometrium compared to healthy controls.•Higher nerve fiber density was linked to more severe pain (higher VAS score).•No association was found between hormone levels and nerve fiber density, and hormonal treatment had no impact on nerve fiber density.•Women with endometriosis had a higher serum allopregnanolone/progesterone ratio, correlated with higher VAS scores.
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.
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.
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.
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. |
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| AbstractList | 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/mm 2 , 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 2 , respectively) compared with healthy controls (1.0 [0.0-u1.0] fibers/mm 2 , 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. •Women with endometriosis had a higher density of PGP9.5-positive nerve fibers in the endometrium compared to healthy controls.•Higher nerve fiber density was linked to more severe pain (higher VAS score).•No association was found between hormone levels and nerve fiber density, and hormonal treatment had no impact on nerve fiber density.•Women with endometriosis had a higher serum allopregnanolone/progesterone ratio, correlated with higher VAS scores. 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. 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. 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. 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. 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. 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. 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 , 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 , respectively) compared with healthy controls (1.0 [0.0-u1.0] fibers/mm , 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. 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. 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.OBJECTIVEThe 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.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.STUDY DESIGNIn 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.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.RESULTSWomen 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.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.CONCLUSIONWomen 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. Highlights•Women with endometriosis had a higher density of PGP9.5-positive nerve fibers in the endometrium compared to healthy controls. •Higher nerve fiber density was linked to more severe pain (higher VAS score). •No association was found between hormone levels and nerve fiber density, and hormonal treatment had no impact on nerve fiber density. •Women with endometriosis had a higher serum allopregnanolone/progesterone ratio, correlated with higher VAS scores. |
| ArticleNumber | 113950 |
| Author | Oral, Engin Turkmen, Sahruh Bäckström, Torbjörn Bahat, Pinar Yalcin Sommar, Anton Özaydin, Ipek Yildiz Bixo, Marie |
| Author_xml | – sequence: 1 givenname: Anton surname: Sommar fullname: Sommar, Anton organization: Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden – sequence: 2 givenname: Pinar Yalcin surname: Bahat fullname: Bahat, Pinar Yalcin organization: Department of Obstetrics and Gynecology, Istanbul Kanui Sultan Suleyman Training and Research Hospital, Istanbul, Turkey – sequence: 3 givenname: Ipek Yildiz surname: Özaydin fullname: Özaydin, Ipek Yildiz organization: Department of Pathology, Istanbul Kanui Sultan Suleyman Training and Research Hospital, Istanbul, Turkey – sequence: 4 givenname: Marie surname: Bixo fullname: Bixo, Marie organization: Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden – sequence: 5 givenname: Torbjörn surname: Bäckström fullname: Bäckström, Torbjörn organization: Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden – sequence: 6 givenname: Engin surname: Oral fullname: Oral, Engin organization: Medical Faculty, Department of Obstetrics and Gynecology, Biruni University, Istanbul, Turkey – sequence: 7 givenname: Sahruh orcidid: 0000-0002-4367-4959 surname: Turkmen fullname: Turkmen, Sahruh email: sahruh.turkmen@umu.se organization: Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden |
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| Snippet | •Women with endometriosis had a higher density of PGP9.5-positive nerve fibers in the endometrium compared to healthy controls.•Higher nerve fiber density was... Highlights•Women with endometriosis had a higher density of PGP9.5-positive nerve fibers in the endometrium compared to healthy controls. •Higher nerve fiber... 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... Objective: The mechanisms behind endometriosis-related pain are not yet fully understood. To determine if there is a difference in the density of endometrial... |
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| SubjectTerms | Adult Allopregnanolone Case-Control Studies EHP30 Endometriosis - blood Endometriosis - complications Endometriosis - pathology Endometriosis - physiopathology Endometrium - innervation Endometrium - pathology Estrogen Female Humans Immunohistochemistry Nerve Fibers - pathology Obstetrics and Gynecology Pain Measurement Pelvic Pain - blood Pelvic Pain - etiology Pelvic Pain - pathology PGP9.5 Progesterone Progesterone - blood Symptom severity |
| Title | Influence of endometrial nerve fibers and hormones on pain in women with endometriosis |
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