The Influence of Central Sensitization in Endometriosis Disease
Conditions: Endometriosis, Adenomatosis
Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study Protocol
Project Name ：
The influence of central
sensitization in
endometriosis disease
Name of the Sponsor: Sun Yat-Sen Memorial Hospital of Sun
Yat-Sen University
Version number: Version 3.0
Version number: April 21, 2025
Project Leader: Yingchen Wu
Plan sign-off confirmation:
Compliance Statement
Comply with the Good Clinical Practice for Drug Trials and the Management Measures for
Investigator-Initiated Clinical Research in Healthcare Institutions (Trial), as well as the Helsinki
Declaration. We commit to implementing this study according to the protocol. Participants must
be trained and the study can only proceed after obtaining written approval from the ethics
committee and informed consent from the participants. Any revisions to the protocol require

re-approval.
Abstract
Endometriosis and adenomyosis are included in endometriotic diseases. Adenomyosis is
similar to endometriosis, both being associated with chronic pelvic pain (CPP), and the involved
pain mechanisms are relatively complex. Currently,Surgical treatment (such as lesion resection,
hysterectomy) is still a common method for treating endometriotic diseases. However, some
patients still have persistent pain after surgery.Recent studies have shown that central sensitization
(CS) may play a significant role in persistent postoperative pain among patients with
endometriosis. Central sensitization refers to the abnormal response of the central nervous system
to pain stimuli, a mechanism that can amplify pain perception, potentially causing pain to persist
even after the lesion has been surgically removed. It is therefore reasonable to hypothesize that
central sensitization may also be a potential contributor to persistent postoperative pain in
adenomyosis patients. Furthermore, the efficacy of different postoperative medications in
alleviating central pain among endometriosis patients remains unclear. Thus, this study aims to
investigate the role of central sensitization in postoperative pain following hysterectomy in
adenomyosis patients, evaluate the pain-relieving effects of different medications after lesion
resection in endometriosis patients, and provide new insights for postoperative pain management.
Introduction
2.1 Background
Endometriosis and adenomyosis are included in endometriotic diseases. Endometrial tissue
appears outside the uterine is called endometriosis. Adenomyosis is a common gynecological
disease in reproductive-aged women. Its characteristic is that endometrial glands and stroma
invade the uterine myometrium, accompanied by the proliferation of surrounding smooth muscle
cells. 20.9% to 34% of reproductive-aged women have adenomyosis detected by ultrasound
examination. Most patients with endometriotic diseases will experience various forms of pain,
such as dysmenorrhea, dyspareunia, chronic pelvic pain, dyschezia, or back pain, etc. Surgical
treatment (such as lesion resection, hysterectomy) is still a common method for treating
endometriotic diseases. However, some patients still have persistent pain after surgery.
The mechanism of central sensitization may explain why about 30% of endometriosis

patients have persistent CPP after traditional surgical treatment. Previous study indicates that
almost half of endometriosis patients (42%) have CS, and CS is independently associated with
moderate to severe chronic pelvic pain, and the score of the Central Sensitization Inventory (CSI)
at the baseline before surgery is significantly correlated with persistent CPP after surgery.
Therefore, it is reasonable to speculate that central sensitization may also be a potential cause of
persistent pain after adenomyosis surgery. However, there is currently no relevant study indicating
whether central sensitization plays a role in persistent pain after hysterectomy in adenomyosis
patients, nor is there any relevant study indicating the pain relief of different medications after
lesion resection in endometriosis patients. In this study, we will explore the role of central
sensitization in pain after hysterectomy in adenomyosis patients, explore the pain relief of
different medications after lesion resection in endometriosis patients, and provide new ideas for
postoperative pain management.
2.2 Risk and Benefit Assessment
2.2.1 Potential risks
This study did not involve clinical interventions, thus there are no risks arising from clinical
procedures.
2.2.2 Known potential benefits
We will explore the role of central sensitization in pain after hysterectomy in adenomyosis
patients, explore the pain relief of different medications after lesion resection in endometriosis
patients, and provide new ideas for postoperative pain management.
Research Objectives and Endpoints
3.1 Purpose
Include 200 or more patients with endometriosis diseases;
Explore the role of central sensitization in postoperative pain of patients with adenomyosis,
that is, the relationship between central sensitization and postoperative pain outcomes (chronic
pelvic pain, dyspareunia, dyschezia, back pain);
Evaluate whether the baseline CSI score can predict the severity of postoperative pain;
Explore the pain relief of different medications after lesion resection in patients with
endometriosis.

3.2. Research indicators
3.2.1 Key Indicators and Definitions
Baseline (preoperative), 1, 3, and 6-month follow-up CSI scores.
3.2.2 Secondary indicators and definitions
Baseline (preoperative), 1, 3, and 6-month follow-up dysmenorrhea scores, chronic pelvic
pain scores, dyspareunia scores, dyschezia scores, back pain scores.
3.2.3 Safety indicators
None.
3.2.4 Other collected metrics
Relevant clinical data such as age, BMI, educational level, history of other diseases, surgical
history, smoking and drinking history, pregnancy and childbirth history, pain duration,
preoperative
CA125
level,
hemoglobin,
surgical
methods
(laparotomy
/
laparoscopy),
endometriosis stage, endometriosis location.
Study population
4.1 Inclusion Criteria:
Patients admitted to the gynaecological ward of Sun Yat-sen Memorial Hospital from March
2025 to March 2027;
Age 18-50 years old;
Endometriosis
focus
excision
or
hysterectomy
(with
or
without
bilateral
salpingo-oophorectomy, with excision of any complicated lesion) ;
The pathology was adenomyosis or endometriosis.
4.2 Exclusion Criteria:
Postmenopausal (spontaneous or surgical) ;
Hysterectomy and/or bilateral salpingo-oophorectomy (before baseline) ;
Lack of CSI or CPP score;
The postoperative follow-up time was less than 6 months.
Research Design
5.1 Overall Design

Inclusion period: From March 2025 to March 2027, a prospective cohort study was
conducted on patients with endometriosis or adenomyosis undergoing surgical treatment in the
gynecology inpatient department of Sun Yat-sen Memorial Hospital, Sun Yat-sen University.
5.2 Research design process
Before enrollment
Surgical treatment
The first month post-operation
The third month post-operation
The 6th month post-operation
5.3 Methods to reduce bias
Endometriosis grouping: Patients were divided
into different
groups
based on age,
lesion
location, postoperative pathology, and fertility
requirements:
GnRH-a
group,
COC
group,
progestogen analogs group, and no medication
required group (non-interventional)
Complete CSI score, pain NRS score
Complete CSI score, pain NRS score
Complete CSI score, pain NRS score
200 people: obtain informed consent, screen potential subjects
according to the inclusion and exclusion criteria, obtain medical
history, and complete the questionnaire (CSI score, pain NRS
score)
adenomyosis group
The
study
was
concluded,
and
statistical analysis was performed.

Multivariate regression analysis was employed to control for potential confounding variables
such as age and BMI, thereby reducing their impact on the results; through standardized
questionnaires (CSI and NRS) and clear evaluation criteria, data collection was ensured to be
consistent across all participants to avoid measurement bias.
5.4 Definition of study completion
The last study subject completed the final follow-up.
5.5 Statistical analysis
5.5.1 Sample size
Exceeds 200 cases;
5.5.2 Data analysis set
This study adopts the Per-Protocol Set (PPS): valid case samples. It is defined as patients
among the subjects who completed all planned treatments, follow-ups, and data collection on
schedule. Any protocol violations or loss to follow-up during the study will result in exclusion
from the Per-Protocol Set.
5.5.3 Statistical Analysis Plan
The statistical analysis software is IBM SPSS Statistics for Windows version 26. Descriptive
statistics will be performed using means and standard deviations for continuous variables, and
frequency analysis for categorical variables. Multiple regression analysis will be employed to
assess the relationship between baseline CSI scores and postoperative pain outcomes (adjusted for
baseline pain levels). Survival analysis or Kaplan-Meier curves will be utilized for comparative
evaluation of the association between postoperative pain relief and central sensitization.
Data collection and management
6.1 Electronic data record
6.2 Data management
The data collection will be conducted in the form of questionnaires; the storage medium is
electronic.
Ethical requirements
This study complies with the "Good Clinical Practice" and the "Management Measures for

Clinical Research Initiated by Researchers in Healthcare Institutions" (Trial Implementation), as
well as the Declaration of Helsinki. Before the commencement of the trial, the study protocol must
be approved by the ethics committee of our institution. During the research process, if protocol
amendments are necessary, the revised protocol must be resubmitted to the ethics committee for
review. Researchers must wait for the ethics committee's approval before implementing the new
protocol.
This study will collect clinical data and personal information of the research subjects for
scientific research purposes, which may involve patients' privacy rights. All participants and data
analysts involved in this study have signed confidentiality agreements and will not disclose
patients' personal information or disease-related details to any individuals or institutions unrelated
to the research. The collected patient data will be uniformly managed to prevent any leakage of
personal privacy.
References
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Association of Central Sensitization Inventory Scores With Pain Outcomes After Endometriosis
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