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The following is a summary of “Influence of endometrial nerve fibers and hormones on pain in women with endometriosis,” published in the March 2025 issue of European Journal of Obstetrics and Gynecology and Reproductive Biology by Sommar et al. 

Researchers conducted a retrospective study to compare the density of endometrial nerve fibers between women with endometriosis and healthy controls and to explore the correlation between nerve fiber density, hormone levels, and symptom severity.  

They included 76 women with endometriosis and 24 healthy controls. The patient group was divided into 2 subgroups: those receiving and not recieving the hormonal treatments. Endometrial biopsies were gathered and stained for protein gene product (PGP) 9.5, a nerve fiber marker. Blood samples were taken for hormone analysis. Pain symptom severity was estimated by the Visual Analog Scale (VAS) and Endometriosis Health Profile (EHP30).  

The results showed that women with endometriosis had a higher endometrial nerve fiber density 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 correlated with more severe pain (β = 0.130 [95% CI: 0.019, 0.240], P = 0.02). Regardless of hormonal treatment, women with endometriosis had higher nerve fiber density (3.0 [2.0–4.0] and 2.0 [1.0–4.0] fibers/mm², respectively) compared to healthy controls (1.0 [0.0–1.0] fibers/mm², both P < 0.001), no substantial differences were observed between those receiving or not receiving hormone treatment. The allopregnanolone/progesterone ratio was higher in untreated women with endometriosis (0.002 [0.001–0.004]) compared to healthy controls (0.001 [0.000–0.005]) and treated women (0.001 [0.000–0.006], P = 0.02 and 0.001, respectively). A higher allopregnanolone/progesterone ratio was linked to more severe pain (β = 20.662 [95% CI: 0.202, 41.121], P = 0.048). However, hormone levels (estrogen, progesterone, and allopregnanolone) were not associated with endometrial nerve fiber density.  

Investigators concluded that women with endometriosis exhibited a greater nerve fiber density in the endometrium, which correlated with more intense pain independent of hormone therapy, and that enhanced progesterone metabolism to allopregnanolone might represent a target for alleviating endometriosis-related pain. 

Source: ejog.org/article/S0301-2115(25)00215-5/fulltext