Influence of endometrial nerve fibers and hormones on pain in women with endometriosis.

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.