ZY5301 Tablet vs Placebo for Treatment of Chronic Pelvic Pain After Pelvic Inflammatory Disease: A Phase 2 Randomized Clinical Trial.

Importance: Chronic pelvic pain (CPP) is the main sequela of pelvic inflammatory disease (PID), with no established treatment. ZY5301 tablets, an effective part preparation extracted from Ajuga decumbens Thunb. (jingucao), are being tested as a treatment for CPP caused by PID. Objective: To evaluate whether ZY5301 tablets are effective and safe for CPP treatment in women with PID. Design, Setting, and Participants: This placebo-controlled double-blind, dose-parallel, phase 2 randomized clinical trial was conducted in 9 hospitals in China. Female participants with CPP after PID were enrolled between October 16, 2020, and August 31, 2021. The data analysis was performed between December 2021 and March 2022. Interventions: Participants were randomized 1:1:1 to receive ZY5301 300 mg/d, ZY5301 600 mg/d, or placebo orally 3 times a day for 12 weeks. Main Outcomes and Measures: Visual analog scale (VAS) scores were the main measure used to evaluate the efficacy of ZY5301 in reducing CPP. The evaluation end points for VAS score included changes in mean weekly VAS score from baseline, area under the VAS score-time curve, pain remission (VAS score of 0 and 1) rate, and median time to pain remission. Safety was evaluated by the occurrence of treatment-emergent and treatment-related adverse events. Results: In total, 180 women were randomly assigned, and 177 were included in the efficacy analysis; thus, the full analysis set included 60 participants in the ZY5301 mg/d group (mean [SD] age, 37.4 [8.1] years), 58 in the ZY5301 600 mg/d group (mean [SD] age, 37.1 [7.9] years), and 59 in the placebo group (mean [SD] age, 38.9 [7.3] years). Participant characteristics at baseline were similar among the groups. After 12 weeks of treatment, the mean (SD) change in VAS score from the baseline was -2.1 (1.7) points, -3.5 (1.5) points, and -3.8 (1.7) points in the placebo, ZY5301 300 mg/d, and ZY5301 600 mg/d groups, respectively (P < .001). The pain remission rates at week 12 were 43.3% and 53.5% in the ZY5301 300 mg/d and ZY5301 600 mg/d groups, respectively, a significant difference compared with the placebo group (11.9%; P < .001). All the other end points showed similar improvements. The ZY5301 600 mg/d group had better efficacy than the ZY5301 300 mg/d group, but the difference was not significant. The safety analysis revealed no significant differences among groups. Conclusions and Relevance: These findings show that ZY5301 tablet is efficacious for the relief of CPP with acceptable tolerability. Trial Registration: ClinicalTrials.gov Identifier: NCT05460546.

Vaginal and rectal microbiome contribute to genital inflammation in chronic pelvic pain.

BACKGROUND: Chronic pelvic pain (CPP) is a multifactorial syndrome that can substantially affect a patient's quality of life. Endometriosis is one cause of CPP, and alterations of the immune and microbiome profiles have been observed in patients with endometriosis. The objective of this pilot study was to investigate differences in the vaginal and gastrointestinal microbiomes and cervicovaginal immune microenvironment in patients with CPP and endometriosis diagnosis compared to those with CPP without endometriosis and no CPP. METHODS: Vaginal swabs, rectal swabs, and cervicovaginal lavages (CVL) were collected among individuals undergoing gynecologic laparoscopy. Participants were grouped based on patients seeking care for chronic pain and/or pathology results: CPP and endometriosis (CPP-Endo) (n = 35), CPP without endometriosis (n = 23), or patients without CPP or endometriosis (controls) (n = 15). Sensitivity analyses were performed on CPP with endometriosis location, stage, and co-occurring gynecologic conditions (abnormal uterine bleeding, fibroids). 16S rRNA sequencing was performed to profile the microbiome, and a panel of soluble immune mediators was quantified using a multiplex assay. Statistical analysis was conducted with SAS, R, MicrobiomeAnalyst, MetaboAnalyst, and QIIME 2. RESULTS: Significant differences were observed between participants with CPP alone, CPP-Endo, and surgical controls for body mass index, ethnicity, diagnosis of ovarian cysts, and diagnosis of fibroids. In rectal microbiome analysis, both CPP alone and CPP-Endo exhibited lower alpha diversity than controls, and both CPP groups revealed enrichment of irritable bowel syndrome-associated bacteria. CPP-Endo exhibited an increased abundance of vaginal Streptococcus anginosus and rectal Ruminococcus. Patients with CPP and endometrioma (s) demonstrated increased vaginal Streptococcus, Lactobacillus, and Prevotella compared to other endometriosis sites. Further, abnormal uterine bleeding was associated with an increased abundance of bacterial vaginosis-associated bacteria. Immunoproteomic profiles were distinctly clustered by CPP alone and CPP-Endo compared to controls. CPP-Endo was enriched in TNF⍺, MDC, and IL-1⍺. CONCLUSIONS: Vaginal and rectal microbiomes were observed to differ between patients with CPP alone and CPP with endometriosis, which may be useful in personalized treatment for individuals with CPP and endometriosis from those with other causes of CPP. Further investigation is warranted in patients with additional co-occurring conditions, such as AUB/fibroids, which add additional complexity to these conditions and reveal the enrichment of distinct pathogenic bacteria in both mucosal sites. This study provides foundational microbiome-immunoproteomic knowledge related to chronic pelvic pain, endometriosis, and co-occurring gynecologic conditions that can help improve the treatment of patients seeking care for pain.

A common problem between gynecology, obstetrics, and reproductive medicine: Cesarean section scar defect.

Approximately 60% of patients undergoing Cesarean sections may develop Cesarean Scar Defect (CSD), presenting a significant clinical challenge amidst the increasing Cesarean section rates. This condition, marked by a notch in the anterior uterine wall, has evolved as a notable topic in gynecological research. The multifactorial origins of CSD can be broadly classified into labor-related factors, patients' physical conditions, and surgical quality. However, conflicting influences of certain factors across studies make it challenging to determine effective preventive strategies. Additionally, CSD manifests with diverse symptoms, such as abnormal uterine bleeding, dysmenorrhea, chronic pelvic pain, dyspareunia, secondary infertility, and Cesarean scar pregnancy. Some symptoms are often attributed to other diagnoses, leading to delayed treatment. The quandary of when and how to manage CSD also adds to the complexity. Despite the development of various therapies, clear indications and optimal methods for specific conditions remain elusive. This longstanding challenge has troubled clinicians in both identifying and addressing this iatrogenic disease. Recent studies have yielded some compelling consensuses on various aspects of CSD. This review aims to consolidate the current literature on every facet of CSD. We hope to raise awareness among clinicians about this clinical problem, encouraging more relevant research to unveil the complete picture of CSD.

Dienogest treatment in women with endometriosis: A retrospective cohort study in Taiwan.

OBJECTIVE: To assess the treatment efficacy of dienogest specifically in the Taiwanese population with endometriosis. MATERIALS AND METHODS: Eighty-eight patients diagnosed with endometriosis receiving at least 3 months of dienogest 2 mg once daily, from January 2018 to June 2022, were enrolled. They were divided into two groups: surgery group and non-surgery group. The assessment of pain improvement was based on visual analog scale (VAS) scores (0-100 mm) recorded at 0, 3, 6, and 12 months following the initiation of dienogest. Serum CA-125 value and ovarian endometrioma size were analyzed at 0 and 6 months. RESULTS: A total of 65 patients with endometriosis presented painful symptoms. In the surgery group (N = 28), the initial VAS score was 47.5 mm, which significantly declined to 9.6 mm at 3 months (p < 0.01), then to 7.5 mm, 2.9 mm, and 2.1 mm at 6, 9, and 12 months, respectively. In the non-surgery group (N = 37), the initial VAS score was 65.7 mm, which significantly declined to 13.2 mm at 3 months (p < 0.01) and 4.9 mm at 6 months (p < 0.05), remained low at 0.3 mm at both 9 and 12 months. Endometrioma size (N = 33) exhibited a significant 35% decrease from 38.2 mm to 24.8 mm after 6 months treatment (p < 0.01). Serum CA-125 levels showed significant improvement from 86.5 to 30.2 U/ml (p < 0.01) at 6 months. CONCLUSION: This retrospective cohort study proved that dienogest is effective in reducing endometriosis-associated pain and endometrioma size in Taiwanese population.

Acute and Chronic Prostatitis.

Prostatitis is a common clinical syndrome classified into four categories: acute bacterial, chronic bacterial, chronic prostatitis/chronic pelvic pain syndrome, and asymptomatic. Bacterial prostatitis (acute and chronic) is primarily diagnosed with history and microbiologic studies, although physical examination can be helpful to localize infection within the genitourinary system. Bacterial prostatitis is treated with antibiotics; the span of treatment is guided by the duration of symptoms and presence of complications. Chronic prostatitis/chronic pelvic pain syndrome is the most common form of prostatitis and is a diagnosis of exclusion with no standardized treatments. Asymptomatic prostatitis does not require treatment and is usually diagnosed incidentally during the workup for other urologic presentations.

A rare cause of pelvic pain: Osteitis pubis treated with steroid injection under fluoroscopy guidance.

Osteitis pubis (OP) is a rare, inflammatory disorder that affects the pubic bone, symphysis, and adjacent structures. OP is reported after urological and gynecological surgeries and documented in athletes. OP is a self-limiting condition, but sometimes symptoms may persist for a long time. Conservative modalities are generally able to treat OP. Here we report a patient treated with a steroid injection under fluoroscopy guidance. A 63-year-old male patient developed pelvic pain after prostate surgery, and the pain was intractable to non-steroidal anti-inflammatory drugs. He underwent a steroid injection under fluoroscopy, and his pain affecting daily living activities and walking was eased for three months.

Prevalence of chronic pelvic pain and associated factors among indigenous women of reproductive age in Ecuador.

BACKGROUND: Chronic pelvic pain is a common disease that affects approximately 4% of women of reproductive age in developed countries. This number is estimated to be higher in developing countries, with a significant negative personal and socioeconomic impact on women. The lack of data on this condition in several countries, particularly those in development and in socially and biologically vulnerable populations such as the indigenous, makes it difficult to guide public policies. OBJECTIVES: To evaluate the prevalence of chronic pelvic pain (dysmenorrhea, dyspareunia, non-cyclical pain) and identify which variables are independently associated with the presence of the condition in indigenous women from Otavalo-Ecuador. DESIGN: A cross-sectional study was carried out including a sample of 2429 women of reproductive age between 14 and 49 years old, obtained from April 2022 to March 2023. A directed questionnaire was used, collected by bilingual interviewers (Kichwa and Spanish) belonging to the community itself; the number of patients was selected by random sampling proportional to the number of women estimated by sample calculation. Data are presented as case prevalence, odds ratio, and 95% confidence interval, with p < 0.05. RESULTS: The prevalence of primary dysmenorrhea, non-cyclic pelvic pain, and dyspareunia was, respectively, 26.6%, 8.9%, and 3.9%.all forms of chronic pain were independently associated with each other. Additionally, dysmenorrhoea was independently associated with hypertension, intestinal symptoms, miscegenation, long cycles, previous pregnancy, use of contraceptives and pear body shape. Pain in other sites, late menarche, exercise, and pear body shape were associated with non-cyclic pelvic pain. And, urinary symptoms, previous pregnancy loss, miscegenation, and pear body shape were associated with dyspareunia. CONCLUSION: The prevalence of primary dysmenorrhea and non-cyclical chronic pelvic pain was notably high, in contrast with the frequency of reported dyspareunia. Briefly, our results suggest an association between dysmenorrhoea and conditions related to inflammatory and/or systemic metabolic disorders, including a potential causal relationship with other manifestations of pelvic pain, and between non-cyclical pelvic pain and signs/symptoms suggesting central sensitization. The report of dyspareunia may be influenced by local cultural values and beliefs.

Comparison of dienogest or combinations with ethinylestradiol/estradiol valerate on the pain score of women with endometriosis: A prospective cohort study.

Endometriosis is one of the most frequent gynecologic disorders. The pathognomonic symptom of endometriosis is pelvic pain. The recommended pain medications are oral hormonal contraceptives, progestin therapy, danazol, gonadotropin-releasing hormone analogs, nonsteroidal anti-inflammatory drugs, and aromatase inhibitors. In this study, we aimed to compare the efficiency of costing dienogest (DNG) and low-cost oral contraceptives regarding visual analog scores (VAS) score of pelvic pain and also cancer antigen-125 (CA-125), anti-Mullerian hormone (AMH) levels, and size of endometrioma in the patients with endometriosis which is a chronic disease that requires a lifelong management plan. In our study, 18 to 45-year-old patients presented to our institution's gynecology and obstetrician department for various complaints over 2 years, and endometriosis diagnoses were included. Patients were divided into 3 groups (20 patients in each medication group) according to the given medication: cyclic DNG (Visanne) or 0.03 mg ethinylestradiol combined with 2 mg DNG (Dienille) or estradiol valerate combined with 2 mg DNG (Qlarista). We recorded all patients' CA-125/AMH values and VAS scores of pelvic pain. All patients gave informed consent. There was no statistically significant difference between pre-medication and post-medication levels of CA-125, AMH, VAS score, and cyst size in all groups. However, statistically, significant decreases were seen in the cyst size and VAS score, indicating response to therapy in all groups. In conclusion, we think it is more reasonable to use cost-effective oral contraceptive medications, which also cause common side effects, instead of costing DNG since all drugs have the same efficiency and success.

Research progress on the relationship between chronic prostatitis/chronic pelvic pain syndrome and the microbiota of the reproductive system.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common pelvic pain syndrome in males, seriously affecting patients' quality of life. For a long time, CP/CPPS has been considered a complex and variable disease, and its pathogenesis remains incompletely understood. Currently, CP/CPPS is believed to be a group of diseases characterized by pelvic pain or discomfort, urinary abnormalities, and other symptoms, each with its unique etiology, clinical characteristics, and outcomes, likely resulting from the action of pathogens or (and) certain non-infectious factors. Traditionally, CP/CPPS was thought to be unrelated to bacterial infections. However, in recent years, with the development of microbiology and the advancement of high-throughput sequencing technology, an increasing number of studies have suggested that microorganisms in the reproductive system may play an important role in the pathogenesis of CP/CPPS. The unique characteristics of CP/CPPS, such as its refractory nature and tendency to recur, may be closely related to the microbiota and their biological functions in the reproductive system. The relationship between CP/CPPS and reproductive system microorganisms is one of the current hot topics in microbiology and urology, receiving considerable attention from scholars in recent years and making a series of new advances. Through this review, we will comprehensively explore the relationship between CP/CPPS and reproductive system microorganisms, and look forward to future research directions, aiming to provide new ideas and methods for clinical diagnosis and treatment, thereby improving the treatment outcomes and quality of life of CP/CPPS patients.

Musculoskeletal evaluation of the lower pelvic complex in women with endometriosis: A case-control study.

OBJECTIVE: Use clinical pain measurement tools to investigate and compare the prevalence of pelvic loin disoders in women with and without endometriosis. STUDY DESIGN: Chronic pelvic pain (CPP) associated with endometriosis has diverse origins, including musculoskeletal factors. Musculoskeletal dysfunction in the pelvic region is theorized to result from sustained muscular contraction, triggered by altered visceral stimuli and adoption of antalgic postures, causing secondary damage to muscles, ligaments, and joints. CPP significantly impacts quality of life, relationships, sexuality, and mental health. However, limited data exists on musculoskeletal impacts of endometriosis and CPP. It was made a case-control study at Maternidade Escola Assis Chateaubriand from August 2017 to January 2021. Evaluated 71 women: 41 in endometriosis group (EG) and 30 in control group (CG). Data collection included sociodemographic questionnaires, musculoskeletal physiotherapeutic evaluations, pain mapping, pressure pain thresholds, kinesiophobia, and disability measurements. Statistical analysis was performed using Spearman's Rho test to determine correlations. RESULTS: Mean age of participants was 31 years. EG exhibited lower pain threshold variations in lumbopelvic trigger points than CG (P < .05). Significant muscle flexibility differences between groups were observed; EG had reduced flexibility (P < .05). Most common pain areas were hypogastrium in EG (48.78 %) and left lumbar in CG (30 %). EG had higher kinesiophobia values (P = .009). There was a weak association between kinesiophobia-pressure threshold association observed in CG's lumbar pelvic region. CONCLUSION: Women with Endometriosis and CPP exhibit higher prevalence of musculoskeletal disorder, lower pain thresholds, decreased lumbopelvic muscle range of motion, higher kinesiophobia scores, and increased disability indices with low back pain compared to healthy women.

Thickness of the abdominal wall and pelvic floor dysfunctions in men who practice crossfit vs no crossfit: An observational study.

INTRODUCTION: The objective of this study is to compare the thickness of the transverse abdominis, internal oblique, external oblique, rectus abdominis, and rectus abdominis distance, the quality of life (SF-36), the presence of chronic pelvic pain (CPPQ-Mohedo), and sexual dysfunction (IIEF) in men who practice CrossFit® versus men who do not. DESIGN, SETTING, PARTICIPANTS, AND MAIN OUTCOME MEASURES: Sixty-four healthy men with an average age of 37.19 were recruited at a private sports club and divided into two groups for this cross-sectional observational study. Additionally, participants completed the CPPQ-M, IIEF, and SF-36 questionnaires. RESULTS: Significant differences were found in the thickness of the internal oblique at rest (p = 0.018, d = 0.61), which was greater in the CrossFit® group. In the SF-36 quality of life questionnaire (p = 0.05, d = 0.50), the CrossFit® group also obtained a higher score. CONCLUSION: CrossFit® improves the quality of life and self-esteem of the participants, in addition to increasing the thickness of the internal oblique. Neither more chronic pelvic pain nor more erectile dysfunction was observed in the CrossFit® group.

Sleep disorders in patients with endometriosis; a cross-sectional study.

BACKGROUND: Endometriosis affects 10-15% of women of reproductive age and is considered a critical gynecological problem. Endometriosis causes pain and infertility, both of which can impair the patient's quality of life. Sleep disorders account for the most bothersome presentation of impaired quality of life. This study investigated the frequency and severity of sleep disorders in women with endometriosis. METHODS: In this analytical cross-sectional study, 665 women referred to three hospitals in Tehran, Rasool-e-Akram, Pars, and Nikan, were included (463 patients with endometriosis and 202 women without endometriosis). All of them were informed about the study design and the aim of the research, and then they were asked to sign the consent form and complete the Pittsburgh Sleep Quality Index (PSQI). After data gathering and entering, they were analyzed by SPSS version 22 and were considered significant with P < 0.05. RESULTS: The study population's mean age was 35.4 ± 7.9 years. The mean global PSQI score in the case group (endometriosis patients) was higher than in the control group (non-endometriosis patients) (10.6 vs. 7.1; P < 0.001). Patients with dyspareunia, dysuria, pelvic pain, and dyschezia had a significantly higher PSQI score (P < 0.05). CONCLUSION: According to the findings of the present study, the sleep quality in endometriosis patients is low, and there is a need to pay greater attention to these patients. This may result in some changes in the therapeutic strategies for this disease.

Amniotic bladder therapy: six-month follow up treating interstitial cystitis/bladder pain syndrome.

INTRODUCTION: Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by chronic pelvic pain and usually accompanies lower urinary tract symptoms. We have previously reported that amniotic bladder therapy (ABT) provides symptomatic improvement in refractory IC/BPS patients for up to 3 months. Herein, we evaluated the durability of ABT up to 6 months. MATERIALS AND METHODS: Consecutive IC/BPS patients received intra-detrusor injections of 100 mg micronized amniotic membrane. Clinical evaluation and patient-reported outcome measurements including Interstitial Cystitis Symptom Index (ICSI), Interstitial Cystitis Problem Index (ICPI), Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS) and Overactive Bladder Assessment Tool (OAB) were assessed. RESULTS: Twenty-five consecutive recalcitrant IC/BPS patients were included in the study with an average age of 47.4 ± 14.4 years (29-67 years). After ABT, the IC/BPS symptoms improved gradually up to 3 months in all patients with an average improvement in ICSI, ICPI, BPIC-SS and OAB score of 72.8%, 71.9%, and 66.6%, (p < 0.001) respectively, at 3 months. At 4 months after ABT, 7 patients experienced a rebound in symptoms and requested another injection which resulted in a significant improvement in IC/BPS symptoms after 2, 4, and 8 weeks (p < 0.01). For the 18 patients who received only one injection, the IC/BPS symptoms were still significantly lower at 5 and 6 months compared to baseline (p < 0.01), suggesting a possible durable effect based on the ICSI, ICPI, BPIC-SS, and OAB questionnaire scores. CONCLUSIONS: ABT provided an improvement in pain and lower urinary tract symptoms up to 6 months post-treatment in some refractory IC/BPS patients.

Case 330.

HISTORY: A 30-year-old female patient with a history of infertility and no pregnancy presented to the gynecologic endometriosis clinic for follow-up 1 month after oocyte retrieval, to be evaluated for pelvic optimization before potential embryo transfer, with worsening dysmenorrhea, dyspareunia, and overall pelvic pain. Eleven years prior, the patient had undergone left ovarian cystectomy for treatment of endometrioma, as well as excision of deep infiltrative endometriosis. The oocyte retrieval procedure, where more than 30 eggs were retrieved, was complicated by ovarian hyperstimulation syndrome and intraperitoneal bleeding, which necessitated admission to the intensive care unit (ICU) for 3 days. Following discharge from the ICU, the patient experienced occasional on-and-off pressure of the urinary bladder and persistent aching pelvic pain. At the 1-month follow-up appointment, the patient's vital signs were assessed (blood pressure, 142/94 mm Hg; pulse rate, 95 per minute; temperature, 96.8 °F [36 °C]). Routine blood investigations, including white blood cell count, were within normal limits. Physical examination showed the abdomen was soft but there was mild pelvic tenderness. The serum ß-human chorionic gonadotropin test result was negative for pregnancy, and urinalysis testing showed no leukocyte esterase or nitrites. MRI of the pelvis (Figs 1-3) was performed to evaluate the worsening pain.

Histopathologic patterns of female genital tuberculosis with clinical correlation: a 10-year (2013-2022) retrospective cross-sectional study.

OBJECTIVE: Underdiagnosis of female genital tuberculosis (FGTB) often leads to infertility. In this study, we aimed to determine the site and histopathologic patterns of FGTB and its correlation with clinical presentation and acid-fast bacilli (AFB) status. METHODS: A retrospective cross-sectional study was conducted on 122 patients with a histopathological diagnosis of FGTB at the Department of Pathology, College of Health Sciences (CHS), Tikur Anbessa Specialized Hospital (TASH), Addis Ababa University (AAU), from January 1, 2013, to August 30, 2022. RESULTS: Female genital tuberculosis was found in 0.94% of the gynecology specimens examined. The most common presentations were menstrual disturbance, abdominopelvic pain, and infertility. Among patients with FGTB, 4.6% exhibited misleading clinical and radiologic findings, leading to suspicion of malignancy and subsequent aggressive surgical management. The endometrium was the most frequently affected organ, followed by the fallopian tube, ovary, cervix, and vulva. In the majority of tuberculous endometritis cases (53.3%), histopathology revealed early-stage granulomas. Acid-fast bacilli were found in a significant proportion (42.6%) of FGTB tissues with TB histopathology. The ovary had the highest rate of AFB detection, followed by the fallopian tube, endometrium, and cervix. CONCLUSION: Female genital tuberculosis should be considered in reproductive-age women presenting with menstrual irregularities, abdominopelvic pain, infertility, or an abdominopelvic mass. The endometrium is commonly affected, displaying early granulomas with low AFB positivity.

Endometriosis, Pain, and Related Psychological Disorders: Unveiling the Interplay among the Microbiome, Inflammation, and Oxidative Stress as a Common Thread.

Endometriosis (EM), a chronic condition in endometrial tissue outside the uterus, affects around 10% of reproductive-age women, significantly affecting fertility. Its prevalence remains elusive due to the surgical confirmation needed for diagnosis. Manifesting with a range of symptoms, including dysmenorrhea, dyschezia, dysuria, dyspareunia, fatigue, and gastrointestinal discomfort, EM significantly impairs quality of life due to severe chronic pelvic pain (CPP). Psychological manifestations, notably depression and anxiety, frequently accompany the physical symptoms, with CPP serving as a key mediator. Pain stems from endometrial lesions, involving oxidative stress, neuroinflammation, angiogenesis, and sensitization processes. Microbial dysbiosis appears to be crucial in the inflammatory mechanisms underlying EM and associated CPP, as well as psychological symptoms. In this scenario, dietary interventions and nutritional supplements could help manage EM symptoms by targeting inflammation, oxidative stress, and the microbiome. Our manuscript starts by delving into the complex relationship between EM pain and psychological comorbidities. It subsequently addresses the emerging roles of the microbiome, inflammation, and oxidative stress as common links among these abovementioned conditions. Furthermore, the review explores how dietary and nutritional interventions may influence the composition and function of the microbiome, reduce inflammation and oxidative stress, alleviate pain, and potentially affect EM-associated psychological disorders.