Central sensitization scores link to pain after endometriosis surgery
Higher central sensitization scores before surgery went with more pain afterward in 239 people with endometriosis. Researchers followed them at one Canadian referral center. The score came from a symptom quiz. Pain fell on average, but people with high scores were more likely to still have high pain.
Key Findings
The cohort had 239 people with endometriosis, followed a mean of 16.1 months after surgery (71.0% follow-up rate). Surgery was conservative for 168 and hysterectomy for 71.
Chronic pelvic pain at follow-up was significantly higher with higher baseline scores (OR, 1.02; 95% CI, 1.00-1.03) after adjusting for baseline pain.
Higher baseline scores also went with more back pain (odds ratio 1.02; 95% CI, 1.00-1.03), deep dyspareunia (odds ratio 1.03; 95% CI, 1.01-1.04) and dyschezia (odds ratio 1.03; 95% CI, 1.01-1.04).
At baseline, 130 patients (54.5%) reported severe chronic pelvic pain. At follow-up, 56 (23.4%) did (P < .001).
The mean Central Sensitization Inventory score moved only from 43.8 to 41.7. Scores stayed high at follow-up in people who started high.
Interpretation
Central sensitization is an amplified pain response in the nervous system. The design can show association only. The questionnaire, the Central Sensitization Inventory, records whole-body symptoms such as poor sleep and low energy. The authors treat it as an indirect marker, and the study ran no nerve-function tests. Everyone came from one referral center for chronic pelvic pain. Of 336 patients, 97 were lost to follow-up. Endometriosis stage was not significantly associated with chronic pelvic pain at follow-up. The authors call for validation in community settings.
RRM Context
Restorative reproductive medicine looks for every cause of a person's pain and treats each one. The surgeons at this center aim to excise all visually suspected lesions. Pain still persisted for some patients, which points to a driver beyond the lesions. A cause-based evaluation therefore covers both the disease and the way the nervous system processes pain.
Our editorial summary of this paper, not the article's abstract.
Abstract
Importance
A subset of people who undergo surgery for endometriosis have persistent pain, suggesting that other factors besides the endometriosis, such as central sensitization, may play a role in this pain. The Central Sensitization Inventory, a validated self-reported questionnaire of central sensitization symptoms, may identify individuals with endometriosis who have more pain after surgery due to pain sensitization.
Objective
To examine whether greater baseline Central Sensitization Inventory scores are associated with postsurgical pain outcomes.
Design, Setting, and Participants
This prospective, longitudinal cohort study performed at a tertiary center for endometriosis and pelvic pain in British Columbia, Canada, included all patients aged 18 to 50 years with diagnosed or suspected endometriosis and a baseline visit between January 1, 2018, and December 31, 2019, who underwent surgery after the baseline visit. Individuals who were menopausal, had a prior hysterectomy, or were missing data for outcomes or measures were excluded. Data analysis was performed from July 2021 to June 2022.
Main Outcomes and Measures
The primary outcome was chronic pelvic pain at follow-up measured on a scale of 0 to 10, with 0 to 3 indicating no pain or mild pain, 4 to 6 indicating moderate pain, and 7 to 10 indicating severe pain. Secondary outcomes were deep dyspareunia, dysmenorrhea, dyschezia, and back pain at follow-up. The main variable of interest was baseline Central Sensitization Inventory score (measured from 0 to 100, consisting of 25 self-reported questions rated from 0 to 4 [never, rarely, sometimes, often, and always, respectively]).
Results
A total of 239 patients (mean [SD] age, 34 [7] years; 189 [79.1%] White [11 (5.8%) identified as White mixed with another ethnicity], 1 [0.4%] Black or African American, 29 [12.1%] Asian, 2 [0.8%] Native Hawaiian or Pacific Islander, 16 [6.7%] other, and 2 [0.8%] mixed race or ethnicity) with follow-up data at more than 4 months after surgery were included in this study (71.0% follow-up rate). The mean (SD) baseline Central Sensitization Inventory score was 43.8 (18.2), and the mean (SD) follow-up was 16.1 (6.1) months. Higher baseline Central Sensitization Inventory scores were significantly associated with higher chronic pelvic pain (odds ratio [OR], 1.02; 95% CI, 1.00-1.03; P = .02), deep dyspareunia (OR, 1.03; 95% CI, 1.01-1.04; P = .004), dyschezia (OR, 1.03; 95% CI, 1.01-1.04; P < .001), and back pain (OR, 1.02; 95% CI, 1.00-1.03; P = .02) at follow-up, when controlling for baseline pain scores. The Central Sensitization Inventory scores themselves decreased slightly from baseline to follow-up (mean [SD] score, 43.8 [18.2] vs 41.7 [18.9]; P = .05); however, individuals with high baseline Central Sensitization Inventory scores still had high scores at follow-up.
Conclusions and Relevance
In this cohort study of 239 patients with endometriosis, higher Central Sensitization Inventory scores at baseline were associated with worse pain outcomes after endometriosis surgery, when controlling for baseline pain scores. The Central Sensitization Inventory could be used to counsel patients with endometriosis on their expected outcomes after surgery.
Rojas HE et al., 2026·Journal of women's health (2002)
To characterize differences between individuals with and without mid-cycle pain in a registry cohort with endometriosis. Prospective analysis of data from the Endometriosis Pelvic Pain Interdisciplinary Cohort Data Registry (Clinicaltrials.gov #NCT02911090) at a tertiary referral center in Western Canada. Three hundred forty-five individuals aged 18-49 years who: (1) had at least one episode of menstrual bleeding in the last 3 months, (2) attended a baseline initial visit, and (3) subsequently had surgery with histological confirmation of endometriosis between January 2018 and December 2023. Exclusion criteria included (1) previous hysterectomy; (2) hormonal suppressive therapy use in the last 3 months; and (3) missing data on mid-cycle pain, history of hormonal therapy use, or menstrual cycle regularity. N/A. Mid-cycle pain in the last month versus No mid-cycle pain in the last month. Of the 345 participants, 67% (n = 232) reported mid-cycle pain in the last month. Mid-cycle pain in the last month was significantly associated with higher mean Central Sensitization Inventory score (48 ± 17 versus 36 ± 16, p < 0.001) and more months of prior hormonal suppressive therapy use (58 [14-120] versus 26 [0-109], p = 0.012). Abnormal anatomy at the time of surgery (e.g., endometrioma, ovarian adhesions) was not associated with mid-cycle pain in the last month. In this endometriosis cohort at a tertiary referral center, most participants reported mid-cycle pain in the last month, which was associated with central sensitization but was not clearly related to endometriosis anatomical distortion.
Bouchard TP et al., 2026·Reproductive biomedicine online·Free to read
Do quantitative urinary hormone measurements on the Mira monitor predict and confirm ovulation accurately compared with ultrasound in women with regular menstrual cycles? Do Mira urine hormones correlate with serum hormones?
This was a prospective, single-centre, blinded diagnostic accuracy study with 52 women aged 19-44 years with regular cycles (24-38 days) who tracked 153 cycles over 18 months. Daily first-morning urine was tested with the Mira monitor for follicle stimulating hormone (FSH), oestrone-3-glucuronide (E13G), luteinizing hormone (LH) and pregnanediol glucuronide (PDG). Serial transvaginal ultrasounds (890 scans) confirmed the day of ovulation. Serum hormones were measured twice per cycle. The 121 ovulatory cycles from 49 participants with sufficient index test and reference standard data were included in the final analysis.
The Mira LH peak day strongly predicted ultrasound-confirmed ovulation (R² = 0.96, P < 0.001; intraclass correlation coefficient = 0.971), with 96% of ovulations occurring within ±1 day. The Mira PDG increase was also strongly associated with ultrasound-confirmed day of ovulation (R² = 0.87, P < 0.001). First-morning urine hormones were significantly associated with serum hormones when collected within 90 min (LH: R² = 0.92; E13G: R² = 0.73; R² = 0.61; R² = 0.75). Anovulatory cycles were identified in 11% of regularly cycling participants.
Quantitative urinary hormone monitoring with the Mira monitor provides accurate prediction and confirmation of ovulation, with strong urine-serum associations supporting reduced reliance on serial serum draws in select patients. These findings support clinical adoption of quantitative urinary fertility monitoring.
Balachandran S et al., 2026·Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC
To assess the impact of the COVID-19 pandemic on reproductive outcomes in patients with recurrent pregnancy loss (RPL) and the influence of material and social deprivation on these outcomes.
This retrospective cohort study included RPL patients seen at a specialized clinic between March 1, 2018, and February 28, 2022. Patients were categorized into two groups based on care period: pre-pandemic (March 1, 2018-February 29, 2020) and pandemic (March 1, 2020-February 28, 2022). Cumulative probabilities of birth were estimated using the cumulative incidence function within a competing risk framework, treating pregnancy loss as a competing event. Fine and Gray regression models calculated sub-distribution hazard ratio (sHR) of birth.
544 patients were included in the study, with 255 in the pre-pandemic group and 289 in the pandemic group. Individuals in the pandemic group were less likely to achieve pregnancy than those in the pre-pandemic group (relative risk = 0.50, 95% confidence interval [CI] 0.39 - 0.66). Among those who conceived, the cumulative probability of live birth was 0.77 in both groups. Relative to individuals residing in high-social deprivation neighborhoods, those living in moderately deprived areas had higher sub-distribution hazards of live birth (adjusted sHR = 1.97, 95% CI 1.25 - 3.10; P = 0.003).
Within specialized RPL care and a universal maternity care system, pregnancy rates were lower during the first two years of the COVID-19 pandemic. However, among those who conceived, the probability of achieving a live birth remained similar between the pre-pandemic and pandemic periods.
Bouchard TP et al., 2026·Reproductive biomedicine online·Free to read
Does formation of the corpus luteum help to identify the day of ovulation on ultrasound when follicular collapse is missed, and how reliable are sonographers versus a review panel in identifying the day of ovulation on ultrasound? Sonographers in a clinic in Canada performed serial endovaginal ultrasound scans (six to eight per cycle) to identify the day of ovulation in regularly cycling women (n = 40) who were followed for one to five cycles (n = 85). The day of ovulation was identified by: (i) identification of the dominant follicle; (ii) disappearance of the dominant follicle; and (iii) identification and dating of the corpus luteum. The main outcome measures were inter-rater reliability between two sonographers, and Bland-Altman agreement between the supervising sonographer and a panel that reviewed each scan to identify the day of ovulation. Of the 85 menstrual cycles reviewed, two cycles did not have sufficient data to date ovulation, one cycle showed an incidental dermoid cyst, and 11 cycles showed anovulatory patterns. This left a total of 71 cycles (84%) for which intra-rater reliability between two sonographers for identifying the day of ovulation was high (intraclass correlation coefficient = 0.99, P < 0.0001), and Bland-Altman agreement showed no significant difference in the estimated day of ovulation between the supervising sonographer and the panel (t = -0.28, P = 0.78). Corpus luteum criteria were necessary to help identify the day of ovulation in 14 of 71 cycles (20%). The estimated day of ovulation can be determined reliably on ultrasound by trained sonographers using collapse of the dominant follicle and formation of the corpus luteum based on six to eight scans per cycle.
A key clinical problem is identifying the patient with endometriosis whose pain is complicated by central nervous system sensitization, where conventional gynecologic treatment (eg, hormonal therapy or surgery) may not completely alleviate the pain. The Central Sensitization Inventory (CSI) is a questionnaire previously validated in the chronic pain population. The objective of this study was an exploratory proof-of-concept to identify a CSI cutoff in the endometriosis population to discriminate between individuals with significant central contributors (identified by central sensitivity syndromes [CSS]) to their pain compared to those without. We analyzed a prospective data registry at a tertiary referral center for endometriosis, and included subjects aged 18 to 50 years with endometriosis who were newly or re-referred to the center in 2018. The study sample consisted of 335 subjects with a mean age of 36.0 ± 7.0 years. An increasing number of CSS was significantly correlated with dysmenorrhea, deep dyspareunia, dyschezia, and chronic pelvic pain scores (P < 0.001), and with the CSI score (0-100) (r = 0.731, P < 0.001). Receiver operating characteristic analysis indicated that a CSI cutoff of 40 had a sensitivity of 78% (95% CI: 72.7%-84.6%) and a specificity of 80% (95% CI: 70.3%-84.5%) for identifying a patient with endometriosis with ≥3 CSS. In the group with CSI ≥ 40, 18% retrospectively self-reported pain nonresponsive to hormonal therapy and 40% self-reported daily pain, compared with 6% and 20% in the CSI < 40 group (P = 0.003 and 0.002, respectively). In conclusion, a CSI ≥ 40 may be a practical tool to help identify patients with endometriosis with pain contributors related to central nervous system sensitization.
Tucker DR et al., 2023·American journal of obstetrics and gynecology
After endometriosis surgery, pain can persist or recur in a subset of patients. A possible reason for persistent pain after surgery is central nervous system sensitization and associated pelvic pain comorbidities. Surgery addresses the peripheral component of endometriosis pain pathophysiology (by lesion removal) but may not treat this centralized pain. Therefore, endometriosis patients with pelvic pain comorbidities related to central sensitization may experience worse pain-related outcomes after surgery, such as lower pain-related quality of life.
This study aimed to determine whether baseline (preoperative) pelvic pain comorbidities are associated with pain-related quality of life at follow-up after endometriosis surgery.
This study used longitudinal prospective registry data from the Endometriosis Pelvic Pain Interdisciplinary Cohort at the BC Women's Centre for Pelvic Pain and Endometriosis. Participants were aged ≤50 years with confirmed or clinically suspected endometriosis, and underwent surgery (fertility-sparing or hysterectomy) for endometriosis pain. Participants completed the pain subscale of the Endometriosis Health Profile-30 quality of life questionnaire preoperatively and at follow-up (1-2 years). Linear regression was performed to measure the individual relationships between 7 pelvic pain comorbidities at baseline and follow-up Endometriosis Health Profile-30 score, controlling for baseline Endometriosis Health Profile-30 and type of surgery received. These baseline (preoperative) pelvic pain comorbidities included abdominal wall pain, pelvic floor myalgia, painful bladder syndrome, irritable bowel syndrome, Patient Health Questionnaire 9 depression score, Generalized Anxiety Disorder 7 score, and Pain Catastrophizing Scale score. Least absolute shrinkage and selection operator regression was then performed to select the most important variables associated with follow-up Endometriosis Health Profile-30 from 17 covariates (including the 7 pelvic pain comorbidities, baseline Endometriosis Health Profile-30 score, type of surgery, and other endometriosis-related factors such as stage and histologic confirmation of endometriosis). Using 1000 bootstrap samples, we estimated the coefficients and confidence intervals of the selected variables and generated a covariate importance rank.
The study included 444 participants. The median follow-up time was 18 months. Pain-related quality of life (Endometriosis Health Profile-30) of the study population significantly improved at follow-up after surgery (P<.001). The following pelvic pain comorbidities were associated with lower quality of life (higher Endometriosis Health Profile-30 score) after surgery, controlling for baseline Endometriosis Health Profile-30 score and type of surgery (fertility-sparing vs hysterectomy): abdominal wall pain (P=.013), pelvic floor myalgia (P=.036), painful bladder syndrome (P=.022), Patient Health Questionnaire 9 score (P<.001), Generalized Anxiety Disorder 7 score (P<.001), and Pain Catastrophizing Scale score (P=.007). Irritable bowel syndrome was not significant (P=.70). Of the 17 covariates included for least absolute shrinkage and selection operator regression, 6 remained in the final model (lambda=3.136). These included 3 pelvic pain comorbidities that were associated with higher follow-up Endometriosis Health Profile-30 scores or worse quality of life: abdominal wall pain (β=3.19), pelvic floor myalgia (β=2.44), and Patient Health Questionnaire 9 depression score (β=0.49). The other 3 variables in the final model were baseline Endometriosis Health Profile-30 score, type of surgery, and histologic confirmation of endometriosis.
Pelvic pain comorbidities present at baseline before surgery, which may reflect underlying central nervous system sensitization, are associated with lower pain-related quality of life after endometriosis surgery. Particularly important were depression and musculoskeletal/myofascial pain (abdominal wall pain and pelvic floor myalgia). Therefore, these pelvic pain comorbidities should be candidates for a formal prediction model of pain outcomes after endometriosis surgery.
Gentles AJ et al., 2025·The journal of pain·Free to read
There is increasing recognition that nociplastic pain and central sensitization may play a role in endometriosis-associated pain. The Pain Sensitivity Questionnaire Minor (PSQ-M) evaluates subjective widespread pain sensitivity, and is linked to pain outcomes in chronic pain populations. However, evidence connecting the PSQ-M to central sensitization in endometriosis is limited. Using the Central Sensitization Inventory (CSI) as a comparison, this study compared the PSQ-M as a clinical proxy for central sensitization in endometriosis individuals. Data collected from 983 endometriosis participants (mean age of 34 years), between January 2020 and December 2022, were analyzed from a prospective registry. A significant but weak positive correlation was observed between PSQ-M and CSI scores (r=0.099, p<0.001). A significant but weak correlation was found between the number of central sensitivity syndromes and pelvic pain-related comorbidities with the PSQ-M (r=0.093, p<0.001), compared to a stronger correlation with the CSI (r=0.687, p<0.05). PSQ-M scores were not significantly associated with baseline (r=0.013, p=0.797) or post-operative (r=-0.046, p=0.801) quality-of-life. There was no change in the PSQ-M and a small change in CSI after endometriosis surgery, suggesting that surgical treatment of endometriosis does not directly address central sensitization. In conclusion, the PSQ-M may not be the optimal clinical proxy for central sensitization in endometriosis. This study evaluates the Pain Sensitivity Questionnaire - Minor (PSQ-M) as a proxy for central sensitization in endometriosis. The PSQ-M showed weak correlations with central sensitivity syndromes and pain scores and was not associated with post-surgical quality-of-life, suggesting it may not be the optimal tool for assessing central sensitization in endometriosis.
Ding A et al., 2024·The journal of sexual medicine·Free full text on PubMed Central
Pelvic pain worsened by orgasm is a poorly understood symptom in patients with endometriosis.
To assess the prevalence of pelvic pain worsened by orgasm in patients with endometriosis and explore its association with potential etiologic factors, including pelvic floor myalgia, uterine tenderness and adenomyosis, and central nervous system sensitization.
An analysis was done of a prospective data registry based at a tertiary referral center for endometriosis. Eligible participants were patients aged 18 to 50 years who were referred between January 1, 2018, and December 31, 2019, diagnosed with endometriosis, and subsequently underwent surgery at the center. Clinical features were compared between participants reporting worsening pelvic pain with orgasm and those without worsening pain with orgasm, including patient-reported variables, physical examination findings, and anatomic phenotyping at the time of surgery. Pelvic floor myalgia and uterine tenderness were assessed by palpation on pelvic examination, adenomyosis by ultrasound, and central nervous system sensitization via the Central Sensitization Inventory (range, 0-100).
Outcomes included pelvic or lower abdominal pain in the last 3 months that worsened with orgasm (yes/no).
Among 358 participants with endometriosis, 14% (49/358) reported pain worsened by orgasm while 86% (309/358) did not. Pain with orgasm was significantly associated with pelvic floor myalgia (55% [27/49] vs 35% [109/309]; Cohen's h = 0.40, P = .01) and higher scores on the Central Sensitization Inventory (mean ± SD, 53.3 ± 17.0 vs 42.7 ± 18.2; Cohen's d = 0.60, P < .001) but not with uterine tenderness or adenomyosis. Other clinical features associated with pain with orgasm were poorer sexual health (higher scores: deep dyspareunia, Cohen's h = 0.60; superficial dyspareunia, Cohen's h = 0.34; and Female Sexual Distress Scale-Revised, Cohen's d = 0.68; all P < .05) and poorer mental health (higher scores: Patient Health Questionnaire-9, 12.9 ± 6.7 vs 9.1 ± 6.3, Cohen's d = 0.59, P < .001; Generalized Anxiety Disorder-7, 9.4 ± 5.6 vs 6.8 ± 5.5, Cohen's d = 0.48, P = .002). Anatomic findings at the time of surgery did not significantly differ between the groups.
Interventions targeting pelvic floor myalgia and central nervous system sensitization may help alleviate pain worsened by orgasm in patients with endometriosis.
A strength is that pain worsened by orgasm was differentiated from dyspareunia. However, pain with orgasm was assessed by only a binary question (yes/no). Also, the study is limited to a single center, and there were limited data on sexual function.
Pelvic pain exacerbated by orgasm in people with endometriosis may be related to concurrent pelvic floor myalgia and central sensitization.
General Gynecology › Pelvic Pain › Chronic Pelvic Pain · Endometriosis › Surgical Treatment › Recurrence After Surgery
Alice J Huang, Yang Doris Liu, Mohamed A Bedaiwy, Christina Williams, Catherine Allaire, Paul J Yong
A Huang, Y Liu, M Bedaiwy, C Williams, Cathy Allaire, Kate Allaire, C Allaire, P Yong
PMID 36848090 36848090 DOI 10.1001/jamanetworkopen.2023.0780 10.1001/jamanetworkopen.2023.0780 Orr et al. 2023, Orr 2023
