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During pregnancy, increased hormonal levels contribute to ligament laxity of the pelvis and could predispose to lumbopelvic pain. The main objective of this study was to assess changes in pregnancy-related hormones, neuromechanical adaptations and clinical pain status throughout pregnancy. An exploratory objective was to examine the possible association between those variables. Twenty-eight pregnant women participated in the study. At each trimester, they provided a blood sample (to measure relaxin, estrogen and progesterone), completed questionnaires assessing clinical status (functional disability, risk of poor prognosis of prolonged lumbar disability, avoidance behaviors, anxiety and pain catastrophizing), and were asked to perform a flexion-relaxation task (erector spinae electromyography and trunk kinematics). Results showed that throughout pregnancy, nocturnal and diurnal lumbopelvic pain intensity and related-disability, risk of poor lumbopelvic pain prognosis as well as avoidance behaviors increased, while pain catastrophizing decreased. Neuromechanical characteristics of flexion-relaxation task, including low back muscle activity and trunk kinematics, were similar across the three trimesters. Positive correlations were found between disability and estrogen levels (changes between first and second trimester, p = 0.05), and estrogen and diurnal lumbopelvic pain intensity (change between second and third trimester, p = 0.02). A positive correlation was also found between weight and the Pelvic Girdle Questionnaire score (changes between second and third trimester, p = 0.05). Negative correlations were found between weight (change between first and second trimester) and lumbopelvic maximal angle (p = 0.003), FRP onset for pelvic (p = 0.04) and lumbopelvic (p = 0.003) angles as well as FRP cessation for lumbopelvic angle (p = 0.001). These results show that, in pregnant women, pain and disability are associated with hormonal changes rather than trunk neuromechanical characteristics during a flexion-relaxation task. These results suggest that the flexion-relaxation task may not be an appropriate proxy to study vertebral and pelvic muscle control in pregnant women., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Daneau et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Abstract: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that is often accompanied by mental health disorders. However, the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain. This study analyzed widely targeted metabolomic data of expressed prostatic secretions (EPS) and plasma to reveal the underlying pathological mechanisms of CP/CPPS. A total of 24 CP/CPPS patients from The Second Nanning People's Hospital (Nanning, China), and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University (Nanning, China) were enrolled. The indicators related to CP/CPPS and psychiatric symptoms were recorded. Differential analysis, coexpression network analysis, and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS. The crucial links between EPS and plasma were further investigated. The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals. Pathway analysis revealed dysregulation of amino acid metabolism, lipid metabolism, and the citrate cycle in EPS. The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes. Moreover, the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS. Overall, metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage, energy metabolism abnormalities, neurological impairment, and immune dysregulation. These alterations may be associated with chronic pain, voiding symptoms, reduced fertility, and depression in CP/CPPS. This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets., (Copyright ©The Author(s)(2024).)

Background: To study and compare the effects of venoactive drug (VAD) therapy and ovarian vein embolization or resection (OVE or OVR, accordingly) on the levels of vasoactive peptides and cytokines in patients with pelvic venous disorders (PeVDs)., Methods: The study included 70 consecutive female patients with PeVD symptoms, such as chronic pelvic pain (CPP), dyspareunia, dysuria, and vulvar varicosities. Based on the results of clinical examination and duplex ultrasound of the pelvic veins, the patients were allocated to the VAD therapy (n = 38) or OVE/OVR (n = 32). Additionally, the enzyme-linked immunosorbent assay tests were performed to determine levels of calcitonin gene-related peptide (CGRP), substance P (SP), interleukins 6 and 8 (IL-6, IL-8) and monocyte chemotactic protein-1 (MCP-1) after a 2-month course of VAD therapy and at 3 months after OVE/OVR., Results: The VAD therapy was associated with a significant decrease in CPP in 84% of patients with PeVD and isolated lesions of the parametrial veins (PVs) and uterine veins (UVs). VAD had no significant effect on the pelvic venous reflux. No changes in the CGRP, SP, IL-6, IL-8, and MCP-1 levels were detected after treatment. At 3 months after OVE or OVR, all patients with PeVD and combined lesions of the ovarian veins (OVs), PVs and UVs reported almost complete relief of CPP. Along with elimination of reflux in ovarian veins, the disappearance of reflux in PVs and UVs was noted. A decrease in the CGRP and SP levels was observed (0.7 ± 0.1 ng/mL and 0.12 ± 0.02 ng/mL before treatment; 0.5 ± 0.12 ng/mL and 0.09 ± 0.06 ng/mL after treatment, respectively; all P < 0.05). No changes in cytokine levels were revealed., Conclusions: Treatment with VAD is associated with the CPP relief, but has no significant effect on the CGRP, SP, IL-6, IL-8, and MCP-1 levels. OVE/OVR results in the CPP relief, elimination of the pelvic venous reflux and a significant decrease in the CGRP and SP levels, but does not change cytokine levels., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Noninvasive biomarkers that predict surgical treatment response would inform personalized treatments and provide insight into potential biologic pathways underlying endometriosis-associated pain and symptom progression., Objective: To use plasma proteins in relation to the persistence of pelvic pain following laparoscopic surgery in predominantly adolescents and young adults with endometriosis using a multiplex aptamer-based proteomics biomarker discovery platform., Study Design: We conducted a prospective analysis including 142 participants with laparoscopically-confirmed endometriosis from the Women's Health Study: From Adolescence to Adulthood observational longitudinal cohort with study enrollment from 2012-2018. Biologic samples and patient data were collected with modified World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project tools. In blood collected before laparoscopic ablation or excision of endometriosis, we simultaneously measured 1305 plasma protein levels, including markers for immunity, angiogenesis, and inflammation, using SomaScan. Worsening or persistent postsurgical pelvic pain was defined as having newly developed, persistent (ie, stable), or worsening severity, frequency, or persistent life interference of dysmenorrhea or acyclic pelvic pain at 1-year postsurgery compared with presurgery. We calculated odds ratios and 95% confidence intervals using logistic regression adjusted for age, body mass index, fasting status, and hormone use at blood draw. We applied Ingenuity Pathway Analysis and STRING analysis to identify pathophysiologic pathways and protein interactions., Results: The median age at blood draw was 17 years (interquartile range, 15-19 years), and most participants were White (90%). All had superficial peritoneal lesions only and were treated by excision or ablation. One-year postsurgery, pelvic pain worsened or persisted for 76 (54%) of these participants with endometriosis, whereas pelvic pain improved for 66 (46%). We identified 83 proteins associated with worsening or persistent pelvic pain 1-year postsurgery (nominal P<.05). Compared with those with improved pelvic pain 1-year postsurgery, those with worsening or persistent pelvic pain had higher plasma levels of CD63 antigen (odds ratio, 2.98 [95% confidence interval, 1.44-6.19]) and CD47 (odds ratio, 2.68 [95% confidence interval, 1.28-5.61]), but lower levels of Sonic Hedgehog protein (odds ratio, 0.55 [95% confidence interval, 0.36-0.84]) in presurgical blood. Pathways related to cell migration were up-regulated, and pathways related to angiogenesis were down-regulated in those with worsening or persistent postsurgical pelvic pain compared with those with improved pain. When we examined the change in protein levels from presurgery to postsurgery and its subsequent risk of worsening or persistent postsurgical pain at 1-year follow-up, we observed increasing levels of Sonic Hedgehog protein from presurgery to postsurgery was associated with a 4-fold increase in the risk of postsurgical pain (odds ratio [quartile 4 vs 1], 3.86 [1.04-14.33])., Conclusion: Using an aptamer-based proteomics platform, we identified plasma proteins and pathways associated with worsening or persistent pelvic pain postsurgical treatment of endometriosis among adolescents and young adults that may aid in risk stratification of individuals with endometriosis., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction and Hypothesis: Bladder pain syndrome (BPS) is poorly understood with both the aetiology and pathophysiology being unknown. Symptoms overlap with other disorders, such as overactive bladder (OAB) and chronic pelvic pain disorders such as endometriosis, making a consensus on how to diagnosis and manage patients challenging. The development of biomarkers for BPS may be the key to understanding more about its pathophysiology, as well as aiding diagnosis, subclassification, and discovering new drug targets for its management. As inflammation is widely understood to hold a central role in BPS, the evaluation of cytokines has gained interest. This article summarises the current literature and understanding of urinary, serum, and bladder tissue cytokines found elevated in patients with bladder pain syndrome., Methods: literature search using Pub Med with the keywords "bladder pain syndrome", "painful bladder syndrome", "bladder pain", "Interstitial cystitis" AND "cytokines" or "inflammation". This study was except from institutional approval., Results: Thirty-six cytokines have been identified as being statistically significantly elevated in either the serum, urine, or bladder tissue of patients with bladder pain syndrome in the 22 studies identified in this review of the literature. These cytokines include those from the interleukin group (n = 14), the CXC chemokine group (n = 5), and the C-C chemokine group (n = 7)., Conclusions: CXCL-1, CXCL-8, CXCL-9, CXCL-10, CXCL-11 from the CXC chemokine group, and CCL2, CCL4, CCL5, CCL7, and CCL11 from the C-C chemokine group have been found to be significantly elevated in patients with bladder pain in the literature. Many of these analytes also have supporting evidence for their roles in bladder pain from animal models and studies in other chronic inflammatory conditions. It is likely that a single cytokine will not serve as an adequate biomarker of disease in bladder pain syndrome for either diagnosis or disease severity. Instead, panels of inflammatory mediators may reveal more about the different pathways of inflammation leading to similar presentations of bladder pain in patients., (© 2024. Crown.)

Background and Objective: Endometriosis (EM) involves the peripheral nervous system and causes chronic pain. Sensory nerves innervating endometriotic lesions contribute to chronic pain and influence the growth phenotype by releasing neurotrophic factors and interacting with nearby immune cells. Calcitonin gene-related peptide (CGRP), a pain-signaling neurotransmitter, has a significant role. This study examines the effect of Dienogest (DNG), a hormone therapy used for managing EM -related pain, on serum CGRP levels in EM patients., Materials and Methods: The Visual Analog Scale (VAS) assessed pain in diagnosed EM., Individuals: Serum samples were obtained to measure CGRP concentration. Participants received a 2 mg/day oral dose of DNG for six months as prescribed treatment. Additional serum samples were collected after this period to measure CGRP levels., Results: In the EM group, 6.7%, 33.3%, and 20% had ovarian EM, ovarian plus uterosacral, and ovarian plus bladder, respectively. The EM group showed higher CGRP serum levels than the control group (80.53 ± 16.13 vs. 58.55 ± 6.93, P < 0.0001). Still, after drug administration, CGRP serum levels significantly decreased compared to pre-treatment levels (69.66 ± 11.53 vs. 80.53 ± 16.13, P < 0.05). The EM group showed higher pain compared to the control group (7.93 ± 1.58 vs. 0.13 ± 0.35, P < 0.0001), but after drug administration, pain significantly decreased compared to pre-treatment levels (1.00 ± 2.00 vs. 7.93 ± 1.58, P < 0.05)., Conclusion: DNG administration reduces pain and serum CGRP levels in EM patients, offering the potential for innovative treatments and tailored options. Understanding neurotransmitter roles and drug effects can aid in discovering more effective modulators for these pathways., (© 2024. The Author(s).)

Purpose: dentification of bioimpedance and clinical features in young men with chronic pelvic pain inflammatory syndrome (CP/CPPS NIH IIIa) depending on the somatotype., Method: s. 150 men of the first period of adulthood from 22 to 35 years old with CP/CPPS NIH IIIa were examined from 2018 to 2022 years. The average age was 31 [28; 34] year. Somatotypes were computed according to Carter and Heath. Body composition was assessed anthropometry and bioimpedance analysis., Results: Ectomorphs had the least clinical, laboratory and instrumental manifestations of CP/CPPS NIH IIIa, the levels of total and free testosterone were the highest. The active cell mass predominated in the component composition of the body. Manifestations in mesomorphs had a moderate degree of severity. Endomorphs had the most severe manifestations of CP/CPPS NIH IIIa, the largest amount of fat mass was noted in the body composition than in men of other somatotypes, the hormonal status was characterized by the lowest levels of free and total testosterone, and the highest level of estradiol., Discussion: Based on the literature data and our own results, it can be assumed that the identified changes in the body component composition and hormonal status of men contribute to the maintenance of chronic inflammation in the prostate, organ ischemia, impaired intracranial metabolism, recurrent course of CP/CPPS NIH IIIa, which significantly reduces the patients quality of life and increases the risk of prostate inflammation with age., Conclusion: Determining the somatotype and conducting a component analysis of body composition allows patients to be divided into groups according to the severity of manifestations of CP/CPPS NIH IIIa. The revealed patterns allow us to classify male endomorphs into the group with the most severe manifestations of CP/CPPS NIH IIIa.

Endometriosis is a common, chronic inflammatory condition, thought to have a higher incidence in symptomatic women, yet, commonly associated symptoms do not always correlate with the presence or severity of disease and diagnosis requires surgery. We prospectively collected data and assessed symptomology and NMR spectroscopy-based metabolomics of 102 women undergoing laparoscopic sterilisation at a tertiary referral centre in a cross-sectional study. Twelve women were incidentally diagnosed with endometriosis (11.7%). According to the pre-operative questionnaire, presence and absence of many symptoms usually attributed to endometriosis were declared at similar frequencies in women with or without endometriosis. Women with endometriosis reported apparently more persistent heavy periods (50% vs 18.9%), prolonged periods (25% versus 7.8%) and problems conceiving (27.3% versus 9%) than those without endometriosis. NMR could not discern any distinguishable differences in the serum metabolome between those with and without endometriosis. Our paper highlights the complex symptomology experienced by women, regardless of a surgical diagnosis of endometriosis. Previous literature and the current study failed to identify clear, distinguishable symptoms or biomarkers pertinent to surgically confirmed endometriosis in the general population. Therefore, development of effective, non-invasive tests for identifying this heterogenous benign condition, endometriosis, is likely to be challenging., (© 2021. The Author(s).)

Objective: To analyze the predictive value of neutrophils, lymphocytes, platelets, neutrophils to lymphocytes ratio (NLR), platelets to lymphocytes ratio (PLR) in identifying the occurrence of post-embolization syndrome (PES) after uterine artery embolization (UAE)., Methods: We conducted a retrospective observational study in a single tertiary care center located in New York City during period of November 2014 - December 2018, for patients who underwent UAE. PES was defined as the occurrence of pelvic pain, nausea or fever within one week after the procedure., Results: We enrolled 62 patients: 12 of them had PES and 50 served as controls. Platelets were statistically significantly higher in patients with PES (p=0.036). Specifically, a platelet count greater than 336×10 3 /uL was identified as cut-off with a specificity of 91.8 %, a sensitivity of 33.3 %, a positive predictive value of 46 % and a negative predictive value of 85 %. The area under the curve (AUC) was 0.721 (CI 0.536-0.907)., Conclusion: Patients with a preprocedural platelet count less than 336×10 3 /uL were less likely to have PES. If confirmed by larger studies, the platelet count could be incorporated into patient counseling and preoperative algorithms to identify the ideal UAE candidates., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Mechanisms of the brain-related comorbidities in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still largely unknown, although CP/CPPS is one of the major urological problems in middle-aged men, while these neuropsychological incapacities considerably diminish life quality. The objectives of this study were to assess behavioral patterns in rats with CP/CPPS and to determine whether these patterns depend on alterations in the brain oxidative stress, corticosterone, and hippocampal parvalbumin-positive (PV+) interneurons. Adult male Wistar albino rats from CP/CPPS (intraprostatic injection of 3% λ -carrageenan, day 0) and sham (0.9% NaCl) groups were subjected to pain and anxiety-like behavior tests (days 2, 3, and 7). Afterwards, rats were sacrificed and biochemical and immunohistochemical analyses were performed. Scrotal allodynia and prostatitis were proven in CP/CPPS, but not in sham rats. Ethological tests (open field, elevated plus maze, and light/dark tests) revealed significantly increased anxiety-like behavior in rats with CP/CPPS comparing to their sham-operated mates starting from day 3, and there were significant intercorrelations among parameters of these tests. Increased oxidative stress in the hippocampus, thalamus, and cerebral cortex, as well as increased serum corticosterone levels and decreased number of hippocampal PV+ neurons, was shown in CP/CPPS rats, compared to sham rats. Increased anxiety-like behavior in CP/CPPS rats was significantly correlated with these brain biochemical and hippocampal immunohistochemical alterations. Therefore, the potential mechanisms of observed behavioral alterations in CP/CPPS rats could be the result of an interplay between increased brain oxidative stress, elevated serum corticosterone level, and loss of hippocampal PV+ interneurons., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2021 Nikola Šutulović et al.)

Objectives: To determine the effect of neurogenic acupoint dry cupping therapy on high sensitive C-reactive protein (hs-CRP) level, pain perception & intensity, and life impact of pelvic pain in women with chronic pelvic pain (CPP), with regard to the biological and neurophysiological impacts of dry cupping on acupoint., Methods: Thirty women with CPP were randomly divided into two equal groups; the study group received dry cupping on neurogenic acupoints plus lifestyle modifications for 8 weeks (n=15), while the control group received only lifestyle modifications for 8 weeks (n=15). Women were assessed pre- and post-rehabilitation program with the hs-CRP blood test, the short-form McGill Pain Questionnaire (SF-MPQ), and the pelvic pain impact questionnaire (PPIQ)., Results: Comparing both groups post-treatment revealed that there were significant reductions in levels of hs-CRP, and scores of SF-MPQ & PPIQ (p<0.05) in the study group compared with the control group. Also, there were significant positive correlations between hs-CRP and both SF-MPQ "Visual Analogue Scale (VAS), Present Pain Intensity (PPI) index & Pain Rating Index (PRI)" and PPIQ (p<0.05)., Conclusion: Neurogenic acupoint cupping therapy had significantly improving effects on the degree of inflammation, pain perception & intensity, and life impact of pelvic pain in women with CPP., Competing Interests: The authors have no conflict of interest.

Altered immune mechanisms are implicated in the pathogenesis of endometriosis. CTLA-4 is a membrane receptor that favors the anergic state of lymphocytes, which may disrupt the immune system response in the endometriotic environment. In this study, we examined the expression of CTLA-4 on T and B cells by flow cytometry and its levels in blood serum and peritoneal fluid by ELISA. Levels of CTLA-4+ T cells were significantly higher in patients with more advanced endometriosis than in those with less advanced disease. Additionally, the negative correlation of CTLA-4 + T lymphocytes and the percentage of NK and NKT-like cells in women with endometriosis and infertility may indicate a different etiopathogenesis of endometriosis accompanying infertility. Our findings shed light on the potential of CTLA-4 in developing new diagnostic and therapeutic approaches in endometriosis management.

Chronic prostatitis/chronic pelvic pain syndromes (CP/CPPS) is a clinical tricky problem due to its enigmatic etiology, low cure rate, and high recurrence rate. The research on its pathogenesis has never stopped. In this experimental autoimmune prostatitis (EAP) model, male C57BL/6 mice were subcutaneously immunized with prostate extracts in an adequate adjuvant. For mice in the antibody intervention group, anti-T2 polyclonal antibodies were intraperitoneally injected during the induction of EAP. Animals were periodically monitored for pelvic pain. Hematoxylin and eosin staining was used to assess prostate inflammation. Tumor necrosis factor-α (TNF-α) levels in serum were measured by ELISA kits. The immunized animals developed prostatitis as a consequence of the immune response against prostate antigens. Pelvic pain thresholds were gradually decreased and TNF-α expression significantly increased. T2 plays an important role in the disease since polyclonal antibodies to T2 greatly ameliorated symptoms in animals induced for EAP. T2 peptide may represent the major autoantigen epitope in EAP, which could serve for a better understanding of the etiology of CP/CPPS.

Some chronic pain conditions and comorbidities suppress the hypothalamic-pituitary-adrenal (HPA) axis and response to dynamic testing. We measured HPA axis responses to corticotropin-releasing hormone (CRH) administration in relation to chronic pelvic pain and endometriosis. In a cross-sectional study of women (n = 54) with endometriosis-associated chronic pelvic pain (n = 22), chronic pelvic pain alone (n = 12), or healthy volunteers (n = 20), adrenocorticotropic-releasing hormone (ACTH) and cortisol levels were measured at 0, 15, 30, and 45 min after intravenous ovine CRH administration. ACTH and cortisol delta (peak-baseline) and area under the curve (AUC) were compared by study group and assessed for association with race and menstrual and non-menstrual pain severity. HPA axis responses did not differ among the racially diverse groups or in those with pain compared with healthy volunteers. However, when stratified by race, ACTH delta (129.9 ± 130.7 vs. 52.5 ± 66.0 pg/mL; p = 0.003), ACTH AUC (4813 ± 4707 vs. 2290 ± 2900 min*pg/mL; p = 0.013), and cortisol delta (26.3 ± 21.5 vs. 13.2 ± 9.7 μg/mL; p = 0.005) were significantly higher in black (n = 10) than predominately white (non-black) subjects (n = 44; 39/44 white). In analyses among primarily white (non-black) women, greater menstrual pain severity was associated with blunted ACTH delta (p = 0.015) and cortisol delta (p = 0.023), and greater non-menstrual pain severity with blunted cortisol delta (p = 0.017). Neuroendocrine abnormalities in women with chronic pelvic pain may differ by pain manifestations and may vary by race. The higher HPA axis response in black women merits investigation in pelvic pain studies stratified by race. In white (non-black) women experiencing pain, a blunted response was related to pain severity suggesting pain affects women independently of endometriosis lesions.

Background: Endometriosis is a long-standing progressive disease that affects women of reproductive age. Macrophage migration inhibitory factor (MIF) is one of non-invasive blood biomarker that was detected in sera of endometriotic patients. The present study aimed to determine the accuracy of serum MIF in diagnosing endometriosis in women with infertility and chronic pelvic pain, and correlate its level to the stage of the disease., Methods: Observational case-control study conducted at Fayoum University hospital from March 2016 till September 2018. Three hundred women candidate for diagnostic laparoscopy for either infertility or gynecologic chronic pelvic pain were included. The study group included patients with symptoms suggestive of endometriosis or chocolate cyst by ultrasound and proved by laparoscopy and histopathology. The control group included other causes of infertility or pelvic pain. All patients undergone either diagnostic or operative laparoscopy, and before laparoscopy blood sampling for quantitative measurement of macrophage migration inhibitory factor (MIF) protein in serum by ELISA technique., Results: The level of serum MIF was significantly higher in endometriosis group compared to control group (1.75 ± 1.48 pg/ml and 0.51 ± 0.45 pg/ ml, respectively, P = < 0.001), with a progressive increase with advancing stage (stage I, 1.3 ± 1.03 pg/ml, stage II, 1.7 ± 1.57 pg/ml, stage III, 2.1 ± 1.19 pg/ml and in stage IV, 3.2 ± 2.6 pg/ml). Moreover, in patients presented with pain and infertile patients showed significantly higher levels of serum MIF (1.92 ± 1.13 vs 1.21 ± 1.17 and 1.82 ± 1.13 vs 1.32 ± 0.91 respectively with p-value < 0.001). ROC curve of serum MIF with a cut off value of 0.85 pg/ml or more achieves a sensitivity of 80.6%, specificity of 83.3%, positive predictive value of 82.9% and negative predictive value of 81.2%., Conclusion: Serum MIF might be a promising marker not only for noninvasive diagnosis of endometriosis but as a target for detecting severity as well.

The aim of this study was to evaluate whether balneotherapy might be effective in patients with chronic pelvic pain (CPP) in the short term. This was an open and prospective pilot study. The balneotherapy programme was performed in a spa resort located in Wando Island, Republic of Korea from August 26 2018 to September 1 2018. It consisted of 10 heated seawater baths (38 °C, 20 minutes) and 10 mud-pack applications (40 °C, 10 minutes) for five days. Sixteen patients were enrolled. Upon analysing responses from a patient questionnaire, we found improvement in parameters such as pain, bladder irrigation symptoms and quality of life after balneotherapy. Inflammatory marker IL-1 and TNF-α was significantly decreased after treatment compared to baseline. There were no adverse events during treatment. Our data suggest that five-day balneotherapy can be beneficial for patients with CPP in the short term.Impact statement What is already known on this subject? The majority of articles in the field of balneotherapy discuss the treatment of rheumatic or dermatological disease. However, data on the effectiveness of balneotherapy for chronic pelvic pain are very limited. What the results of this study add ? Our study suggests that balneotherapy can be beneficial for patients with CPP in the short-term. The duration of balneotherapy was five days, which is shorter than that of the European studies. Intuitively, it may be doubtful whether short-term therapy has any practical effect. As most people living in Korea have a vacation period of about one week each in summer and winter, the choice of a five-day programme in our study reflects the reality of vacation schedules. What the implications are of these findings for clinical practice and/or further research? Further studies are necessary to demonstrate the persistence of these benefits on the long term, as well as their existence in appropriate control group and different duration of treatment.

Objective: Genital endometriosis (GE) is a widespread gynecological disease which requires its further pathogenesis investigation and search for new effective treatments. The known data of oxytocin receptor presence in endometrioid heterotopy smooth muscle cells give some grounds to assume oxytocin participation in the pathogenesis of endometriosis. The present study objective was to evaluate oxytocin level in peripheral blood (PB) in patients with endometriosis associated pain syndrome and to estimate the efficacy of oxytocin receptor inhibitors (IOXTR) administration based on animal endometriosis model., Materials and Methods: The basic group comprised 61 patients with endometriosis associated pain syndrome, while 21 patients formed the control group. VAS, MPQ, and BBS objective tests were applied for pain syndrome evaluation. Oxytocin level in PB was measured by immunoenzyme method. After confirmation of endometriosis experimental model formation in rats and further randomization, a daily IOXTR intra-abdominal injection was performed in a dose of 0.35 mg/kg/24 h in the basic group ( n  = 12) or saline solution administration in the control ( n  = 12). On the final stage, endometrioid heterotopy size measuring was performed along with histological examination., Results: Oxytocin level in PB was authentically higher in patients with GE compared to the control: 51.45 (35.54-62.76) pg/mL and 27.64 (23.23-34.12) pg/mL, respectively ( p <.001). Positive correlation between oxytocin PB level and pain syndrome expression was established in patients with GE: VAS ( r  = 0.76; p <.001), MPQ ( r  = 0.52; p <.001), and BBS ( r  = 0.57; p <.001). Based on the experimental disease model authentical decrease of endometrioid heterotopy average area was observed after IOXTR therapy compared to the control (7.3 ± 1.8 mm 2 and 22.2 ± 1.2 mm 2 , respectively, p <.05)., Conclusions: The obtained results confirm the oxytocin role in the pathogenesis of endometrioid associated pain syndrome. The high efficacy of IOXTR administration based on animal model of surgically induced endometriosis allows viewing this method as a perspective therapy.

Background: Vaginal diazepam is frequently used to treat pelvic floor tension myalgia and pelvic pain despite limited knowledge of systemic absorption., Aim: To determine the pharmacokinetic and adverse event profile of diazepam vaginal suppositories., Methods: We used a prospective pharmacokinetic design with repeated assessments of diazepam levels. Eight healthy volunteers were administered a 10-mg compounded vaginal diazepam suppository in the outpatient gynecologic clinic. Serum samples were collected at 0, 45, 90, 120, and 180 minutes; 8, 24, and 72 hours; and 1 week following administration of a 10-mg vaginal suppository. The occurrence of adverse events was assessed using the alternate step and tandem walk tests, the Brief Confusion Assessment Method, and numerical ratings. Plasma concentrations of diazepam and active long-acting metabolites were measured. Pharmacokinetic parameters were calculated by standard noncompartmental methods., Results: The mean peak diazepam concentration (C max ) of 31.0 ng/mL was detected at a mean time (T max ) of 3.1 hours after suppository placement. The bioavailability was found to be 70.5%, and the mean terminal elimination half-life was 82 hours. The plasma levels of temazepam and nordiazepam peaked at 0.8 ng/mL at 29 hours and 6.4 ng/mL at 132 hours, respectively. Fatigue was reported by 3 of 8 participants., Clinical Implications: Serum plasma concentrations of vaginally administered diazepam are low; however the half-life is prolonged., Strengths & Limitations: Strengths include use of inclusion and exclusion criteria aimed at mitigating clinical factors that could adversely impact diazepam absorption and metabolism, and the use of an ultrasensitive LC-MS/MS assay. Limitations included the lack of addressing the efficacy of vaginal diazepam in lieu of performing a pure pharmacokinetic study with healthy participants., Conclusion: Vaginal administration of diazepam results in lower peak serum plasma concentration, longer time to peak concentration, and lower bioavailability than standard oral use. Providers should be aware that with diazepam's long half-life, accumulating levels would occur with chronic daily doses, and steady-state levels would not be reached for up to 1 week. This profile would favor intermittent use to allow participation in physical therapy and intimacy. Larish AM, Dickson RR, Kudgus RA, et al. Vaginal Diazepam for Nonrelaxing Pelvic Floor Dysfunction: The Pharmacokinetic Profile. J Sex Med 2019;16;763-766., (Copyright © 2019. Published by Elsevier Inc.)

We investigated the clinical characteristics of patients with varicocele according to the presence or absence of scrotal pain. We retrospectively reviewed the records of patients who underwent varicocelectomy. The age, body mass index, grade, laterality of varicocele, testicular volume difference, time to hospital visit, serum testosterone level and semen parameters were evaluated. A total of 954 patients were included. The painful group had lower mean age, lower BMI, higher grade of varicocele, smaller testicular volume difference and shorter time to hospital visit than the painless group. In addition, the median serum total testosterone level and total sperm count, concentration and motility were higher in the painful group than in the painless group. In multivariate analysis, there were significant differences between the two groups in age, grade of varicocele, testis volume difference, time to hospital visit, total sperm count and concentration. Patients with painful varicocele visited hospital earlier because of the pain and tended to start treatment sooner. They were also younger, had smaller testis atrophy and had higher sperm concentration, even though they had a higher grade of varicocele than patients without pain. Although scrotal pain in varicocele patients is difficult to treat, it leads to early diagnosis and treatment., (© 2018 The Authors. Andrologia Published by Blackwell Verlag GmbH.)

Objective: The aim of the study was to assess the serum levels of the following biomarkers in women with endometriosis-associated pelvic pain before and after six months of using the etonogestrel (ENG) contraceptive implant or the 52 mg levonorgestrel-releasing intrauterine system (LNG-IUS): cancer antigen (CA)-125, cluster of differentiation (CD) 23 and endometrial nerve fibre density., Methods: The study was conducted at the Department of Obstetrics and Gynaecology, University of Campinas Medical School, Brazil. A total of 103 women with endometriosis-associated pain diagnosed by surgery, transvaginal ultrasound and/or magnetic resonance imaging were included. Endometrial nerve fibre density and serum levels of CA-125 and soluble CD23 were assessed before and after six months of using the allocated method and were correlated to 10 cm visual analogue scale (VAS) scores for non-cyclical pelvic pain and dysmenorrhoea., Results: Both contraceptive methods significantly reduced concentrations of serum soluble CD23 and endometrial nerve fibre density (p < .001); however, CA-125 was significantly reduced only among users of the ENG implant (p < .05). No correlation was observed between reduction of biomarkers and improvement of VAS pain and dysmenorrhoea scores. No differences were observed between the ENG implant and the LNG-IUS., Conclusion: Both progestin-only contraceptives significantly reduced two out of the three biomarkers evaluated. These two biomarkers could, therefore, be used as surrogate markers to follow up medical treatment of endometriosis-associated pain.

A mouse model was developed to simulate the clinical features of chronic prostatitis/chronic pelvic pain syndrome using peptide (T 2 ). Forty C57BL/6 mice were divided into four groups of 10 mice each, averagely and randomly. T 2 plus aluminium hydroxide adjuvant group was given subcutaneous injection with the emulsion mixture of T 2 and aluminium hydroxide adjuvant, the T 2 group with T 2 , the aluminium hydroxide adjuvant group with aluminium hydroxide adjuvant and the normal control group with 0.9/% NaCl solution. Haematoxylin andeosin staining was used to observe the inflammation of the prostate. Plasma levels of TNF-α and CRP were detected by ELISA kit. The expression of IL-1βin the prostate was investigated by immunohistochemistry. The statistical differences between the groups were compared by t test. Histopathological analyses demonstrated that prostate lesions were most severe in the group immunised with T 2 plus aluminium hydroxide adjuvant. Plasma levels of TNF-α and CRP were statistically elevated compared with control groups. The expression levels of IL-1β in the prostate were more obvious than control groups. T 2 in aluminium hydroxide adjuvant subcutaneous injection could successfully set up experimental autoimmune prostatitis in C57BL/6 mice. This murine model would be greatly beneficial to further comprehend the aetiology, pathogenesis and explicit treatment of CP/CPPS., (© 2017 Blackwell Verlag GmbH.)

Purpose: Immune mechanisms have been hypothesized to contribute to the development of CP/CPPS. In this study, we investigated the differential expression of immune factors between patients with CP/CPPS and healthy volunteers., Methods: This study was registered in Australian New Zealand Clinical Trials Registry. Healthy volunteers and patients with CP/CPPS were enrolled in this study. The inclusion criteria for patients were below: (1) aged 18-45 years old; (2) prostatitis-related syndrome longer than 3 months; (3) normal routine urine culture and negative bacterial culture in prostatic fluid. Patients were further classified into two groups: types IIIA and IIIB CP/CPPS according to the results of EPS routine test. Serum immune markers include IgA, IgM, IgG, CD4 + and CD8 + ., Results: There are total 23 CP/CPPS patients, including 12 type IIIB and 11 type IIIA. Relatively, there are 26 healthy volunteers. The serum levels of IgG were higher in CP/CPPS patients compared to healthy volunteers (1141.2 ± 204.3 vs 1031.9 ± 173.7 mg/L, p = 0.045), while the serum levels of CD8 + were lower in CP/CPPS patients compared to healthy volunteers (492.8 ± 185.6 vs 640.0 ± 246.8 cells/μL, p = 0.021). Furthermore, serum levels of IgG were higher in patients with IIIA CP/CPPS compared to those with IIIB (1244.3 ± 151.6 vs 1054.3 ± 209.3 mg/L, p = 0.023)., Conclusions: Differential levels of IgG and CD8 + between CPPS patients and healthy volunteers suggest a contributing role of immune mechanisms to the development of CP/CPPS; and IgG may play an important role in inflammatory CPPS. Clinical Study registration number ACTRN12613000792729.

Objective: To investigate the usefulness of soluble galectin-9 (Gal-9) in the noninvasive laboratory diagnosis of endometriosis and various gynecologic disorders., Design: Prospective case-control study., Setting: University medical centers., Patient(s): A total of 135 women of reproductive age were involved in the study, 77 endometriosis patients, 28 gynecologic controls, and 30 healthy women., Intervention(s): Diagnostic laparoscopy and collection of tissue biopsies, peritoneal cells, and native peripheral blood from different case groups of gynecology patients and healthy women., Main Outcome Measure(s): The expression of mRNA and serum concentration of Gal-9., Result(s): Semiquantitative reverse transcription-polymerase chain reaction analysis and serum soluble Gal-9 ELISA were performed on three different cohorts of patients: those with endometriosis, those with benign gynecologic disorders, and healthy controls. Differences in the Gal-9 concentrations between the investigated groups and the stability of Gal-9 in the serum and diagnostic characteristics of Gal-9 ELISA were determined by statistical evaluation and receiver operating characteristic (ROC) curve analysis. Significantly elevated Gal-9 levels were found in both minimal-mild (I-II) and moderate-severe (III-IV) stages of endometriosis in comparison with healthy controls. At a cutoff of 132 pg/mL, ROC analysis revealed an excellent diagnostic value of Gal-9 ELISA in endometriosis (area under the curve = 0.973) with a sensitivity of 94% and specificity of 93.75%, indicating better diagnostic potential than that of other endometriosis biomarkers. Furthermore, various pelvic pain or infertility-associated benign gynecologic conditions were also associated with increased serum Gal-9 levels., Conclusion(s): Our results suggest that Gal-9 could be a promising noninvasive biomarker of endometriosis and a predictor of various infertility or pelvic pain-related gynecologic disorders., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective. To study features of histamine metabolism in patients with chronic pelvic pain associated with external genital endometriosis. Methods. For quantitative assessment of histamine level in peripheral blood was taken from 100 patients which than was centrifuged. In blood serum histamine concentration was determined by enzyme-linked immunosorbent assay method with reagents «Histamine ЕLISA» on the machine BAE-1000 Histamine (Labor Diagnostika Nord - LDN, Hermany). A pain syndrome was assessed by Visual Analog Scale (VAS), quality of life assessment - by Endometriosis Health Profile Questionnaire (EHR-30), level of anxiety was determined by Spielberger-Khanin questionnaire. The results. Showed statistically higher histamine level in patients with severe pain according to VAS. After assessment of results obtained from Spielberger-Khanin questionnaire 100% experimental group's women with external genital endometriosis (n = 60) were noted to be have high level of state and trait anxiety, then 40% women of control group (n = 16) have moderate level of anxiety. The incidence of depression in women with chronic pelvic pain was 58.3% (n = 35) and the main part (n = 20) were women with severe stage of pelvic pain according to VAS. Conclusions. Psycho emotional condition of women with external genital endometriosis associated pelvic pain characterized by higher depression and anxiety levels, with significant decrease quality of life. Direct relationship also was found between pain syndrome intensity and histamine level in peripheral blood in patients with external genital endometriosis.

Background: Qian-Yu decoction (QYD) is a traditional Chinese medicinal recipe composed of Radix astragali (Astragalus membranaceus (Fisch.) Bunge var. mongholicus (Bunge) P.K. Hsiao, Fabaceae ), Herba epimedii (Epimedium brevicornum Maxim., Berberidaceae), Herba leonuri (Leonurus japonicus Houtt., Lamiaceae), Cortex phellodendri (Phellodendron chinense Schneid., Rutaceae) and Radix achyranthis bidentatae (Achyranthes bidentata Bl., Amaranthaceae). This study aimed to evaluate the therapeutic activity of QYD against carrageenan-induced chronic prostatic/chronic pelvic pain syndrome (CP/CPPS) in rats and further elucidate its effective components., Methods: Three types of components, total polysaccharides, total flavonoids and total saponins were separately extracted from QYD. Carrageenan-induced CP/CPPS rats were intragastrically administered with lyophilized product of QYD, individual extracts and all the combined forms of extracts for three weeks. Prostatic index (PI) was determined and histopathological analysis was performed. The levels of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), cyclooxygenase-2 (COX-2) and prostaglandin E2 (PEG2) in rat prostate tissues were measured using ELISA. The production of inducible nitric oxide synthase (iNOS) was evaluated by an enzymatic activity assay, and the release of nitric oxide (NO) was determined by a nitrate/nitrite assay., Results: Treatment with QYD significantly ameliorated the histological changes of CP/CPPS rats and reduced the PI by 44.3%, with a marked downregulation of TNF-α (42.8% reduction), IL-1β (45.3%), COX-2 (36.6%), PGE2 (44.2%), iNOS (54.1%) and NO (46.0%). Each of three extracts attenuated the symptom of CP/CPPS, but much more weakly than QYD. The combined administration of three extracts showed efficacy comparable to that of QYD while better than that of any combination of two extracts. A principal component analysis of the six inflammatory mediators as variables indicated that the effects of TS on CP/CPPS were rather different from those of TF and TP, which were similar., Conclusions: QYD can be beneficial in prevention and treatment of CP/CPPS. Polysaccharides, flavonoids and saponins, as the major effective components of QYD, exert a cooperative effect on CP/CPPS.

Objective: To compare the efficacy and acceptability of combined hormonal vaginal ring with combined oral hormonal pill in women with idiopathic chronic pelvic pain., Study Design: Randomised prospective interventional trial conducted in 60 women with idiopathic chronic pelvic pain. Women were randomised into two groups of 30 each. In each group, treatment was given for 84 days using either combined vaginal ring or combined oral hormonal pill. Hormonal vaginal ring releases 15mcg of ethinyl estradiol and 120mcg of the etonogestrel per day while the hormonal pill contained 30mcg of ethinyl estradiol and 150mcg of levonorgestrel. There was no ring or pill free week. After every 28 days, pain relief was measured using visual analogue scale (VAS), and verbal rating score (VRS) calculated by summing dysmenorrhea, non-cyclic pelvic pain (NCCP) and deep dyspareunia scores. Side effects, compliance, satisfaction, and user acceptability were also measured. Data was analyzed using various parametric and non-parametric tests., Results: Reduction in mean VAS score at end of treatment in ring group was 6.23 (95% confidence interval [CI], 5.45-7.01; p<0.001) as compared to 5.53 in pill group (95% CI, 4.83-6.23; p<0.001). Reduction in mean VRS score was 5.63 in ring users (95% CI, 4.84-6.42; p<0.001) versus 4.36 in pill users (95% CI, 3.63-5.10; p<0.001). A significantly higher persistent relief in NCPP score was observed in vaginal ring group as compared to oral pill group at end of one month after stopping treatment. Compliance, satisfaction, and user acceptability were higher in ring users (80%) than pill users (70%) and a higher incidence of nausea was seen in pill group., Conclusion: Present study demonstrates for first time that both vaginal and oral hormonal therapy are effective in treatment of idiopathic chronic pelvic pain and vaginal ring may be a better choice with higher satisfaction rate and fewer side effects., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Pelvic pain is typically associated with pelvic inflammatory disease (PID). The most common cause of PID is Chlamydia trachomatis. The aim of this study was to verify the role of serological testing for Chlamydia trachomatis in patients with suspected PID., Materials and Method: The retrospective study included 185 patients with pelvic pain hospitalized at the Department of Obstetrics and Gynecology in 2003 and 2004. Titers of anti-Chlamydia trachomatisIgG and IgA were measured by means ELISA immunoassays. Erythrocyte sedimentation rate (ESR), serum concentration of C-reactive protein (CRP) and leukocyte count (WBC) were also determined. Final diagnosis was established on the basis of laparoscopic examination., Results: The presence of anti-Chlamydia trachomatis antibodies correlated significantly with abnormal values of ESR, WBC and CRP. The most common laparoscopic pathology were pelvic adhesions, typically found in women with elevated titers of anti-Chlamydia trachomatis IgG. Cconclusion. Serological examination for Chlamydia trachomatis is helpful in evaluation of patients with suspected PID. Elevated titers of anti-Chlamydia trachomatis antibodies are frequently associated with laparoscopic evidence of pelvic adhesions and inflammation.

Objective: To examine the impact of validation and temporal resolution of estimation of hCG increase, because patients' hCG values are not obtained at precise daily increments or always in the same laboratory., Design: Retrospective cohort study of women presenting with nondiagnosed symptomatic first-trimester pregnancies who had serial hCG level measurements over time., Setting: Not applicable., Patient(s): A total of 171 women presenting from September 2007 to February 2010 with first-trimester pregnancy pain and/or bleeding for whom a normal intrauterine pregnancy was ultimately confirmed., Interventions: None., Main Outcome Measure(s): Serial hCG values, time period between hCG measurements, hCG rise., Result(s): After data verification, 118 subjects contributing 327 values met inclusion criteria and passed data verification for analysis with improved temporal precision. The more precise data showed a steeper hCG rise, and the predicted 2-day hCG increase at the 1st percentile was slightly faster (1.68-fold vs. 1.56-fold) than the "raw" clinical data and previous models., Conclusion(s): Data verification and improved temporal precision suggested a faster hCG increase in early intrauterine gestation than previously demonstrated. Because laboratory variation and temporal imprecision are common, these data demonstrate that current modeling of the expected rise of hCG in a normal gestation is valid and appropriately conservative in the determination of a nonviable gestation. No change in the minimal threshold for potential viability is recommended., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: A recent study investigated the role of testosterone (T) in chronic prostatitis or chronic pelvic pain syndrome (CP/CPPS). However, only a small amount of data is available to date, and the results are inconsistent., Aims: To evaluate the relation between total T (TT) and CP/CPPS., Methods: We conducted a propensity-matched study by identifying men with a TT level lower than 3.5 ng/mL among 8,336 men in their 40s and 50s. A control group of men with a TT level of at least 3.5 ng/mL matched for age, metabolic syndrome, and body mass index at a 5:1 ratio was selected for comparison. Using the same cohort and methods, another case group (TT < 3.0 ng/mL) and control group (TT ≥ 3.0 ng/mL) were selected. The National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) was administered. A χ(2) test, a t-test and logistic regression analyses were used to evaluate the relation between TT and prostatitis-like symptoms., Main Outcome Measures: Association of TT with NIH-CPSI score., Results: After propensity score matching, 948 cases (TT < 3.5 ng/mL) and 4,740 controls (TT ≥ 3.5 ng/mL) were included. The ratio of mild and moderate to severe prostatitis-like symptoms was higher in the case group than in the control group (24.0% vs 27.4%, P = .001). The ratio of moderate to severe prostatitis-like symptoms also was higher in the case group than in the control group (6.2% vs 9.2%, P = .028). The pain domain of the NIH-CPSI, quality of life, and total NIH-CPSI scores also were higher in the case group. Ratios of severe lower urinary tract symptoms (12.6% vs 15.1%, P = .044) to maximal flow rate no higher than 10 mL/sec (3.8% vs 5.3%, P = .044) and postvoid residual urine volume of at least 100 mL (4.0% vs 5.6%, P = .035), which suggest high pressure in the prostate urethra, were higher in the case group. After adjusting for voided volume during uroflowmetry and total prostate volume, the relations of a TT level lower than 3.5 ng/mL to a maximal flow rate no higher than 10 mL/sec (odds ratio = 1.402, 95% CI = 1.017-1.934, P = .039) and to a postvoid residual urine volume of at least 100 mL (odds ratio = 1.410, 95% CI = 1.031-1.927, P = .031) were maintained. Using the cutoff TT value of 3.0 ng/mL, 437 cases (TT < 3.0 ng/mL) and 2,185 controls (TT ≥ 3.0 ng/mL) were included. The result of the 3.0-ng/mL cutoff value for TT showed a higher incidence of prostatitis-like symptoms in the group with a TT level lower than 3.0 ng/mL, but this was not statistically significant., Conclusion: Low TT level (<3.5 ng/mL) was significantly correlated with prostatitis-like symptoms in this study., (Copyright © 2016. Published by Elsevier Inc.)

Background: Recent studies demonstrated low-grade inflammation in patients with irritable bowel syndrome (IBS). However, these studies have been relatively small and do not enable examination of this factor in different subtypes of IBS and the possibility of confounding effects of comorbidities that may be associated with inflammatory responses., Goals: To investigate the association between high-sensitive C-reactive protein (hs-CRP) and the diagnosis of IBS, IBS subtypes, symptoms' severity, and IBS-associated comorbidities., Study: This cross-sectional study uses data from a large matched case-control study of IBS subjects and healthy controls (HC). hs-CRP levels were measured in all subjects. IBS diagnosis was determined by Rome III criteria, negative screening blood tests, and normal colonoscopy. Subjects were evaluated for IBS severity and associated pain and psychological comorbidities., Results: A total of 242 IBS patients and 244 HC were studied. Median hs-CRP levels in the IBS group were significantly higher than in HC (1.80; interquartile range, 0.7 to 4.04 mg/L vs. 1.20, interquartile range, 0.5 to 2.97 mg/L respectively, P<0.006). Levels were highest in IBS-D patients with greater disease severity. Hs-CRP levels mildly correlated with symptoms severity (r=0.169, P=0.009); this correlation was stronger for the IBS-D patients (r=0.27, P=0.006). IBS was a significant independent predictor (P=0.025) for higher hs-CRP levels, whereas other pain and psychological comorbidities were not., Conclusions: Given these observations of cross-sectional differences in hs-CRP between IBS subtypes and severity, independent of pain and comorbidities, more research is needed to explore a possible role of low-grade inflammation in the pathogenesis and/or clinical presentation of IBS.

Objective: To define the utility of serum carcinogenic antigen (CA)-125 and CA 19-9 combining pain score in the prediction of pelvic endometriosis in infertile women., Materials and Methods: Serum CA-125 and CA 19-9 were measured using immunoradiologic methods during the follicular phase preceding laparoscopy for infertility. Values obtained were correlated with the occurrence and severity of endometriosis. Receiver operating characteristic (ROC) curve was applied to assess the utility of serum CA-125, CA 19-9, and pain score in preoperative preparation. Cut-off value of CA-125 and CA 19-9 was defined., Results: The study enrolled 294 infertile women receiving laparoscopy between July 2010 and September 2011. Ninety-four patients were diagnosed with endometriosis and 200 patients without. Preoperative serum CA-125 and CA 19-9 levels were significantly different between the two groups. ROC curve analyses of serum CA-125 and CA 19-9 set a cut-off value of 18.25 IU/ml and 13.15 IU/ml, producing a sensitivity of 64.8% and 84.8%, a specificity of 81.9% and 51.6%, a positive predictive value (PPV) of 63.6% and 46.1%, and a negative predictive value (NPV) of 81.0% and 87.4%, respectively. Combined-analyses of CA-125 and CA 19-9 produced a sensitivity of 72.4%, a specificity of 81.9%, a PPV of 62.3%, and a NPV of 81.8%. Combined-analyses of serum CA-125, CA 19-9 and pain score produced a sensitivity of 71.0% and a specificity of 74.0%., Conclusions: Preoperative CA-125 and CA 19-9 levels combining pain score can be useful for the prediction of pelvic endometrinsis and may he included in the evaluation of unexulained infertile women.

Purpose of Investigation: To assess the accuracy of CA-125 determination associated with clinical history and of the neutrophil/lymphocyte (N/L) ratio for a presumptive diagnosis of endometriosis in women with chronic pelvic pain (CPP)., Materials and Methods: This was a cross-sectional study of data from the medical records of women with CPP submitted to laparoscopy from August 1999 to January 2009 at the University Hospital. The performance of the evaluation of CA-125 and of the N/L ratio for the prediction of endometriosis was compared based on the corresponding ROC curves and their 95% confidence intervals., Results: CA-125 levels were significantly higher in women with CPP and endometriosis and their association with a complaint of dysmenorrhea improved their sensitivity. For a cut-off of 20 IU/ml, the predictive value for a diagnosis of endometriosis in women with CPP was 97.6%. Dyspareunia, subfertility, and N/L ratio were not useful for a diagnosis of endometriosis in women with CPP., Conclusion: The association of elevated CA-125 levels with a complaint of dysmenorrhea is adequate in a presumptive and accurate diagnosis of endometriosis in this specific group of women with CPP, permitting an early institution of clinical treatment without the need of previous laparoscopic confirmation.

The objective of this prospective study was to determine the plasma levels of nitric oxide (NO) in women with chronic pelvic pain secondary to endometriosis (n=24) and abdominal myofascial pain syndrome (n=16). NO levels were measured in plasma collected before and 1 month after treatment. Pretreatment NO levels (μM) were lower in healthy volunteers (47.0±12.7) than in women with myofascial pain (64.2±5.0, P=0.01) or endometriosis (99.5±12.9, P<0.0001). After treatment, plasma NO levels were reduced only in the endometriosis group (99.5±12.9 vs 61.6±5.9, P=0.002). A correlation between reduction of pain intensity and reduction of NO level was observed in the endometriosis group [correlation = 0.67 (95%CI = 0.35 to 0.85), P<0.0001]. Reduction of NO levels was associated with an increase of pain threshold in this group [correlation = -0.53 (-0.78 to -0.14), P<0.0001]. NO levels appeared elevated in women with chronic pelvic pain diagnosed as secondary to endometriosis, and were directly associated with reduction in pain intensity and increase in pain threshold after treatment. Further studies are needed to investigate the role of NO in the pathophysiology of pain in women with endometriosis and its eventual association with central sensitization.

Objective: The immune system has been implicated as one mechanism underlying the benefits of acupuncture therapy. Evidence suggests that acupuncture can ameliorate symptoms of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), but the association between clinical response and the immune system has not been investigated., Design/setting: We investigated 12 CP/CPPS patients participating in a prospective randomized clinical trial comparing acupuncture versus sham acupuncture for effects on cellular immunity. Blood samples were taken before the first needling and after the last of 20 treatment sessions (week 10). Patients also completed questionnaires examining their CP/CPPS symptoms and mood status at the baseline and end of study visits., Results: At the end of study 8 of 12 participants (67%) were classified as treatment responders, four participants each from the acupuncture and sham groups. The acupuncture group averaged a 5% increase in natural killer cell levels compared to corresponding sham (-13%; p=0.03). Similarly, patients randomized to acupuncture reported a reduction in other white blood cell parameters examined, supporting the possibility that immunity might be important in the pathophysiology of CP/CPPS., Conclusions: The specific effect of acupuncture on CP/CPPS remains unclear. Further research is warranted to examine the mechanisms by which acupuncture therapy may improve clinical symptoms in patients with CP/CPPS., Trial Registration: ClinicalTrials.gov number, NCT00260637)., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To investigate the relationship of the common Traditional Chinese Medicine (TCM) syndrome pattern of chronic pelvic pain syndrome (CPPS) with the contents of substance p and beta endorphin in the plasma, and provide reference data for the clinical diagnosis, differentiation and treatment of CPPS by TCM., Methods: We observed 98 cases of CPPS, which were classified into a lower-part damp-heat invasion group (group A, n = 32), a blood stasis-induced collateral obstruction group (group B, n = 34), and a damp-heat stagnation group (group C, n = 32) according to the TCM syndrome differentiation. Another 35 normal healthy young men were enrolled as controls. We measured the contents of substance p and beta endorphin in the plasma by immunoradiometry and ELISA, and analyzed their relationship with the TCM syndrome pattern., Results: The contents of plasma substance p were significantly higher in groups A ([1135.76 +/- 166.45] pg/ml), B ([1 337.84 +/- 170.81] pg/ml), and C ([1 210.01 +/- 162.27] pg/ml) than in the control ([574.99 +/- 113.09] pg/ml) (all P < 0.01), while the contents of plasma beta endorphin in groups A ([212.70 +/- 29.49] pg/ml), B ([157.99 +/- 24.01] pg/ml), and C ([180.81 +/- 20.20] pg/ml) were remarkably lower than that in the control ([274.73 +/- 27.64] pg/ml) (all P < 0.01)., Conclusion: In the plasma of CPPS patients, the content of substance p is significantly elevated and that of beta endorphin markedly reduced, which suggests that they may be involved in the inflammatory reaction of CPPS. The levels of plasma substance p and beta endorphin can be used as valuable reference for the TCM classification of chronic prostatitis.

This Phase 2 study evaluated the safety and efficacy of elagolix for treating endometriosis-associated pain. A total of 155 women with laparoscopically confirmed endometriosis were randomized to placebo, elagolix 150 mg, or elagolix 250 mg once daily for 12 weeks. Placebo patients were rerandomized to elagolix and elagolix patients continued their dosing assignment for 12 additional weeks; the primary efficacy measure was changed from baseline in the monthly mean numerical rating scale for pain at week 12. Monthly mean (standard error of the mean) reductions were greater with elagolix versus placebo (-1.19 ± 0.18, -1.25 ± 0.18, and -0.88 ± 0.18 for elagolix 150 mg, 250 mg, and placebo, respectively); differences were not statistically significant. Monthly mean dysmenorrhea and nonmenstrual pelvic pain scores were reduced with elagolix, with significant differences for dysmenorrhea at weeks 8 and 12 versus placebo (P < .05). Minimal bone mineral density changes were observed with elagolix treatment. In women with endometriosis-associated pain, elagolix demonstrated an acceptable efficacy and safety profile in this Phase 2 study.

Objective: The aim of this study was to identify changes in inflammatory molecules in the blood (plasma) of patients with chronic prostatitis/chronic pelvic syndrome (CP/CPPS) compared with controls. Altered levels indicate a systemic component by possible involvement of the prostate and/or the inner pelvic floor musculature., Material and Methods: In 32 patients with CP/CPPS and 37 controls, blood plasma levels of testosterone, macrophage migration inhibitory factor (MIF), tumour necrosis factor-α (TNF-α), TNF-β, interleukin-2 (IL-2) and IL-1β were measured by enzyme-linked immunosorbent assay. Cortisol in saliva samples was measured in the morning and late evening. All participants answered a questionnaire regarding their health profile., Results: Significantly higher levels of MIF (p = 0.012) were detected in patients. The testosterone level was, contrary to other studies, little lower in patients (p = 0.014; age adjusted). When controls with health issues and patients with a parallel disease were excluded, the MIF and TNF-α levels were higher in the patients (p = 0.007, p = 0.016, respectively) than in controls, and the testosterone was slightly lower in patients (p = 0.047)., Conclusions: The findings show an immune response extending to the circulatory system, in which MIF makes a significant contribution to CP/CPPS. This study also indicates TNF-α as a circulatory component when excluding subjects with concomitant diseases. Both MIF and TNF-α have previously been highlighted for other diseases related to chronic pain and here also for CP/CPPS. These results provide further insights into the immunological basis of CP/CPPS.

A 44-year-old man is presented here with 14 years of chronic purulent sinusitis, a chronic fungal rash of the scrotum, and chronic pelvic pain. Treatment with antifungal therapy resulted in symptom improvement, however he was unable to establish an effective long-term treatment regimen, resulting in debilitating symptoms. He had undergone extensive work-up without identifying a clear underlying etiology, although Candida species were cultured from the prostatic fluid. 100 genes involved in the cellular immune response were sequenced and a missense mutation was identified in the Ras-binding domain of PI3Kγ. PI3Kγ is a crucial signaling element in leukotaxis and other leukocyte functions. We hypothesize that his mutation led to his chronic infections and pelvic pain.

Objectives: To reevaluate both discriminatory and threshold levels associated with visualization of gestational sacs, yolk sacs, and fetal poles in patients presenting with vaginal bleeding, pain, or vaginal bleeding and pain in the first trimester of pregnancy using current ultrasonographic technology., Methods: We reviewed the records of patients with first-trimester vaginal bleeding, pelvic pain, or both who were evaluated with a serum β-hCG level and a transvaginal ultrasonogram within 6 hours of each other and had a known pregnancy outcome. Discriminatory and threshold β-hCG levels for visualization of a gestational sac, yolk sac, and fetal pole were identified for all ultimately viable pregnancies. Logistic regression was used to model the predicted probability of visualizing these structures as a function of β-hCG values using fractional polynomials., Results: Six hundred fifty-one pregnancies met inclusion criteria; 366 were viable. Discriminatory β-hCG levels at which structures would be predicted to be seen 99% of the time were 3,510 milli-international units/mL, 17,716 milli-international units/mL, and 47,685 milli-international units/mL for gestational sac, yolk sac, and fetal pole, respectively. In our population, threshold values for β-hCG levels at which these structures could be seen were 390 milli-international units/mL, 1,094 milli-international units/mL, and 1,394 milli-international units/mL, respectively., Conclusions: Improvements in ultrasonographic technology have led to lower threshold β-hCG values for ultrasonographic visualization of early intrauterine gestational structures. However, discriminatory levels for serum β-hCG levels were higher than values currently used in practice., Level of Evidence: II.

Objective: To investigate the hCG profiles in a diverse patient group with ectopic pregnancy (EP) and to understand when they may mimic the curves of an intrauterine pregnancy (IUP) or spontaneous abortion (SAB)., Design: Retrospective cohort study., Setting: Three university hospitals., Patient(s): One hundred seventy-nine women with symptomatic pregnancy of unknown location., Intervention(s): None., Main Outcome Measure(s): Slope of log hCG; days and visits to final diagnosis., Result(s): Of women with an EP, 60% initially exhibited an increase in hCG values, with a median slope of 32% increase in 2 days; 40% of subjects initially had an hCG decrease, with the median slope calculated as a 15% decline in 2 days. In total, the hCG curves in 27% of women diagnosed with EP resembled that of a growing IUP or SAB. Of the EP hCG curves, 16% demonstrated a change in the direction of the slope of the curve. This was more common in African Americans and less evident in Hispanics. Furthermore, it was associated with more clinical visits and days until final diagnosis., Conclusion(s): The rate of change in serial hCG values can be used to distinguish EP from an IUP or SAB in only 73% of cases. The number of women who had a change in direction of serial hCG values was associated with race and ethnicity., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The study examined symptomatology in 74 patients with chronic abacterial prostatitis. The features of blood lipid metabolism in inflammatory and noninflammatory forms of disease are redefined. Dynamic characteristics of arterial blood flow in the prostate gland of patients with chronic abacterial prostatitis are determined. Comparative analysis between groups revealed significant differences in some indices of blood lipid profile, and arterial flow velocity parameters of the prostate in patients studied; correlations between the intensity of pain, the type of dyslipoproteinemia and arterial ischemia of the prostate are shown. The feasibility of analysis of the blood lipoprotein spectrum in the differential diagnosis of inflammatory and noninflammatory forms of chronic abacterial prostatitis is demonstrated.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition that adversely affects men across a wide range of ages. A number of pharmacologic and nonpharmacologic therapies for CP/CPPS have been investigated. Our study aimed to evaluate the prevalence of CPPS in Korean men in their thirties and to investigate the effect of CPPS and medical treatment on semen quality. Of 314 men with prostatitis, 74 patients with CPPS class IIIA (23.6%) were eligible for the study; these patients underwent combined α-blocker and cyclo-oxygenase 2 inhibitor therapy. These 74 men were prospectively studied at a medical center in Seoul, Korea. A number of parameters, including ejaculations per month, semen variables, and the levels of hormones (such as follicle-stimulating hormone, estradiol [E(2)], luteinizing hormone [LH], testosterone, and prolactin) were evaluated. The mean number of ejaculations per month, the mean number of daily hours spent sitting at work, smoking, body mass index, LH and E(2) levels, and semen parameters all showed significant differences (P < .0001) between the study patients and the controls. The combined regimen was effective in improving all aspects of semen quality except morphology (P < .05). CPPS class IIIA, which is notably prevalent among Korean men in the fourth decade of life, affects semen quality and poses a challenge to fertility. Proper treatment of CPPS class IIIA results in improved semen quality. Men with CPPS therefore require proper evaluation and treatment by andrologists/urologists before planning a natural conception.

Objective: To evaluate serum concentrations of CA-125 and soluble CD-23 and to correlate them with clinical symptoms, localization and stage of pelvic endometriosis and histological classification of the disease., Methods: Blood samples were collected from 44 women with endometriosis and 58 without endometriosis, during the first three days (1st sample) and during the 7th, 8th and 9th day (2nd sample) of the menstrual cycle. Measurements of CA-125 and soluble CD-23 were performed by ELISA. Mann-Whitney U test was used for age, pain evaluations (visual analog scale) and biomarkers concentrations., Results: Serum levels of CA125 were higher in endometriosis patients when compared to the control group during both periods of the menstrual cycle evaluated in the study. This marker was also elevated in women with chronic pelvic pain, deep dyspareunia (2nd sample), dysmenorrhea (both samples) and painful defecation during the menstrual flow (2nd sample). CA-125 concentration was higher in advanced stages of the disease in both samples and also in women with ovarian endometrioma. Concerning CD-23, no statistically significant differences were observed between groups., Conclusion: The concentrations of CA-125 were higher in patients with endometriosis than in patients without the disease. No significantly differences were observed for soluble CD-23 levels between groups.

We compared 47 patients with groin pain following hip resurfacing to a matched control group. Functional scores and plain radiographs were assessed along with measurement of whole blood cobalt and chromium by inductively coupled mass spectrometry. Symptomatic patients underwent ultrasound scan of the affected hip. Mean functional outcomes were poor in those with pain and good in the control group. Groin pain was associated with valgus stem positioning and lower neck:head ratio (relatively narrow neck) (p=0.03, p=0.04 respectively). We classified patients with groin pain into two groups: biological and mechanical. The biological group had soft tissue abnormalities on USS and higher levels of cobalt and chromium (p=0.04, p=0.05 respectively). The mechanical group had normal USS, lower metal ion levels and more retroverted femoral components (p=0.01).

Purpose: We determined the soluble B7-H3 level and its clinical significance in serum and expressed prostatic secretions of patients with chronic prostatitis, including chronic bacterial prostatitis (type II) and chronic pelvic pain syndrome., Materials and Methods: Using enzyme-linked immunosorbent assay we measured soluble B7-H3 in 11 patients with chronic prostatitis (type II), and 26 with inflammatory (type IIIA) and 54 with noninflammatory (type IIIB) chronic pelvic pain syndrome, and healthy donors. We assessed differences between these groups using Student's t test. As determined by the National Institutes of Health-Chronic Prostatitis Symptom Index, we correlated soluble B7-H3 with clinical pain using the Pearson test., Results: We found no significant difference between serum soluble B7-H3 in healthy donors and patients with chronic prostatitis (p = 0.897). However, soluble B7-H3 in expressed prostatic secretions was statistically significantly decreased in patients with chronic prostatitis vs controls (p <0.001). ROC using soluble B7-H3 greater than 38.82 ng/ml in expressed prostatic secretions distinguished patients with chronic prostatitis from healthy donors with 90.9% sensitivity and 83.5% specificity. Also, soluble B7-H3 levels in expressed prostatic secretions correlated negatively with the Chronic Prostatitis Symptom Index and the pain subscore. Compared to the pretreatment level soluble B7-H3 in expressed prostatic secretions was significantly increased in patients with a greater than 25% decrease in the Chronic Prostatitis Symptom Index total score (p = 0.016)., Conclusions: Data indicate that the soluble B7-H3 level in expressed prostatic secretions is a novel chronic prostatitis marker that correlates negatively with subjective symptoms., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Endometriosis is a benign gynecologic disease defined as the presence of functional endometrial glands and stroma outside the uterine cavity, causing dysmenorrhea, dyspareunia, menstrual irregularities, and infertility. Serum CA-125 measurement is now a consolidated method for diagnosing this condition, and its interpretation has posed a number of problems, particularly regarding utility in diagnosing minimal-mild endometriosis, whereas its value as a diagnostic aid in moderate-severe stages is well recognized. In our cohort, serum CA-125 values were significantly elevated in patients with ovarian and mixed endometriosis lesions (median levels 48 U/mL), compared with those who had exclusively extraovarian foci (median levels 27 U/mL), and so the correlation between this marker and the surgical and pathologic finding of ovarian and deep endometriosis was found to be statistically significant; however, the location did not affect the fertility rate., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether interleukin-8 (IL-8) serum levels are correlated with pelvic pain in patients with ovarian endometriomas., Design: Prospective study., Setting: Tertiary-care university hospital., Patient(s): Interleukin-8 serum levels were prospectively analyzed in 51 patients (group A, asymptomatic patients or patients with mild dysmenorrhea; group B, severe dysmenorrhea and/or chronic pelvic pain and/or dyspareunia) who underwent surgery for cystic ovarian endometriosis to asses whether a correlation exists between IL-8 serum levels and pelvic pain., Intervention(s): Interleukin-8 serum levels determination., Main Outcome Measure(s): Interleukin-8 serum levels and pelvic pain., Result(s): From 56 patients, five cases were ultimately excluded because the histologic diagnosis was not cystic ovarian endometriosis (2 teratomas and 3 haemorragic cysts). The mean (+/-SD) IL-8 serum levels in group A were 6.41 +/- 12.17 pg/mL and in group B were 6.52 +/- 8.73 pg/mL., Conclusion(s): Pain symptoms in ovarian endometriosis is not correlated with IL-8 serum levels., (Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Primary dysmenorrhea is a common disorder among young women, and uterine ischemia plays an important role in pelvic pain. Asymmetric dimethylarginine (ADMA) is accepted as a strong marker of endothelial dysfunction., Objective: To investigate the role of ADMA in primary dysmenorrhea., Methods: Thirty-three patients with primary dysmenorrhea and 29 healthy controls were evaluated in a hospital outpatient clinic-based study. Secondary causes of dysmenorrhea had been ruled out in each patient. LDL cholesterol, triglycerides measured and body mass index were also calculated. Blood samples for determination of ADMA concentration were drawn on the 3rd day of menses in each woman. Groups were compared for statistically significant difference by Mann-Whitney U test., Results: Groups did not differ in age or hormone levels. ADMA level was higher in women with dysmenorrhea compared to healthy controls (Mann-Whitney U test, Z = -2.24, p = 0.025). ADMA levels showed positive correlation with age and erythrocyte sedimentation rate in the first group (Spearman's rho = 0.360, p = 0.040, and r = 0.379, p = 0.029, respectively). Although erythrocyte sedimentation rate and C-reactive protein (CRP) were positively correlated, no significant correlations were found between high-sensitivity CRP and ADMA level in the first group (Spearman's rho = 0.048, p = 0.749)., Conclusion: ADMA concentrations are elevated in primary dysmenorrhea compared to healthy controls. This suggests that endothelial dysfunction plays a role in primary dysmenorrhea., (Copyright 2009 S. Karger AG, Basel.)

Objectives: To evaluate the efficacy and safety of Serenoa repens + selenium and lycopene (Profluss) versus S. repens alone for the treatment of category IIIa chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)., Patients and Methods: 102 patients with IIIa CP/CPPS were enrolled and randomized into two groups each to receive Profluss or S. repens alone for 8 weeks. Evaluation was based on results of the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), IPSS, maximum peak flow rate (MPFR), and PSA measurements at baseline and at weeks 4, 8 and 8 after the end of treatment. The primary endpoint was a >50% reduction in NIH-CPSI score. Secondary endpoints evaluated were MPFR, IPSS, PSA and white blood cell count., Results: No patients withdrew from the study. The mean NIH-CPSI score decreased significantly (p < 0.001) in both groups; we observed a decrease in the total score from 27.45 to 13.27 in group 1 (-51.64%) and from 27.76 to 20.62 in group 2 (-26.06%). IPSS improved significantly (p < 0.001) in both arms, but more in group 1. PSA and white blood cell count decreased significantly (p < 0.007) only in group 1. The MPFR improved more in group 1 (p < 0.005)., Conclusion: Profluss is a triple therapy that is safe and well tolerated. It ameliorates symptoms associated with IIIa CP/CPPS., (Copyright (c) 2010 S. Karger AG, Basel.)