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Problem: Various chemokines have been linked to endometriosis. Notably, chemokines such as CCL2, CXCL8, and CXCL1 have also been shown to promote nociception. In this study, it was investigated whether increased serum concentrations and endometrial expression of chemokines (specifically CCL2, CXCL8, and CXCL1) are associated with heightened severity of pain symptoms in women with endometriosis.

Method of Study: The study included women with endometriosis (with [n = 27] and without[n = 24] hormonal treatment) as well as healthy controls (n = 22). All participants underwent blood sampling and an endometrial biopsy during the secretory phase of the menstrual cycle. Symptom severity in the patient group was assessed using the pain dimension of the 30-item Endometriosis Health Profile (EHP-30) and a visual analog scale (VAS) for pain.

Results: Serum levels of CCL2 and CXCL1, as well as endometrial expression of CXCL8, were lower in women with endometriosis compared to controls. Furthermore, increased serum levels of CCL2, CXCL8, and CXCL1 were associated with higher EHP-30 pain domain scores in women with endometriosis. Similarly, elevated endometrial expression of CXCL8 andCXCL1 correlated with higher VAS scores. Notably, when the patient group was stratified based on ongoing hormonal treatment, CXCL1 emerged as the most promising target, with both increased serum concentration and endometrial expression consistently being associated with greater symptom severity.

Conclusions: The results suggest that chemokines may play a role in the severity of pain symptoms experienced by women with endometriosis, and CXCL1 stands out as a potential therapeutic target. 

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.

Introduction: The mechanism underlying endometriosis-related pain remains poorly understood. Previous studies have indicated that γ-aminobutyric acid (GABA) type A (GABAA) receptors and GABAergic substances (eg endogenous neurosteroids) play important mechanistic roles in various pain conditions. Our primary objective was to compare GABAA receptor function between women with endometriosis and healthy controls by performing a challenge test with diazepam, a GABAA receptor agonist, using the saccadic eye velocity as the main outcome. The secondary objective was to investigate the relationship between GABAA receptor function and serum levels of allopregnanolone, an endogenous positive modulator of the GABAA receptor, in the participating women.

Material and methods: 15 women with pelvic pain and laparoscopically confirmed endometriosis and 10 healthy, symptom-free, control women, aged 18–40 years, underwent the diazepam challenge test during the follicular phase of the menstrual cycle. Basal serum allopregnanolone levels were measured prior to diazepam injection.

Results: Compared with healthy controls, women with pelvic pain and confirmed endometriosis had a significantly smaller change in saccadic eye velocity after GABAA receptor stimulation with diazepam, indicating lower sensitivity to diazepam. The saccadic eye velocity response was not correlated with the serum allopregnanolone levels.

Conclusions: Women with painful endometriosis show altered GABAA receptor function, depicted as a muted response to an exogenous GABAA receptor agonist.

Objective: To assess pain symptoms before and after hysterectomy in women with endometriosis.

Design: A population-based registry study.

Setting: Sweden.

Population: Women aged 18-45 years who underwent hysterectomy for endometriosis between 2010 and 2015.

Methods: Pain symptoms before hysterectomy and 12 months after surgery were collected from the Swedish National Quality Register for Gynaecological Surgery (GynOp). Pain symptoms were also assessed by follow-up surveys after a median follow-up period of 63 months.

Main outcome measures: Pelvic or lower abdominal pain after hysterectomy.

Results: The study included 137 women. The proportion of women experiencing pain of any severity decreased by 28% after hysterectomy (P < 0.001). The proportion of women with severe pain symptoms decreased by 76% after hysterectomy (P < 0.001). The majority of women (84%) were satisfied with the surgical result. Presence of severe pain symptoms after the hysterectomy was associated with less satisfaction (P < 0.001). Pain symptoms after surgery, patient satisfaction and the patient's perceived improvement were not significantly different between women whose ovarian tissue was preserved and women who underwent bilateral oophorectomy.

Conclusions: We observed a significant, long-lasting reduction in pain symptoms after hysterectomy among women with endometriosis. Hysterectomy, with the possibility of ovarian preservation, may be a valuable option for women with endometriosis who suffer from severe pain symptoms.

Tweetable abstract: Hysterectomy is a valuable option for women with endometriosis and severe pain symptoms.