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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Published in:European journal of obstetrics & gynecology and reproductive biology Vol. 310; p. 113950
Main Authors: Sommar, Anton, Bahat, Pinar Yalcin, Özaydin, Ipek Yildiz, Bixo, Marie, Bäckström, Torbjörn, Oral, Engin, Turkmen, Sahruh
Format: Journal Article
Language:English
Published: Ireland Elsevier B.V 01.06.2025
Subjects:
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
Immunohistochemistry
EHP30
PGP9.5
Estrogen
Progesterone
Symptom severity
Allopregnanolone
ISSN:0301-2115, 1872-7654, 1872-7654
Online Access:Get full text
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Summary:•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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ISSN:0301-2115
1872-7654
1872-7654
DOI:10.1016/j.ejogrb.2025.113950