Plasma proteins and persistent postsurgical pelvic pain among adolescents and young adults with endometriosis.

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.

Cytokines in Bladder Pain Syndrome: A Review of the Literature.

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.

CGRP neuropeptide levels in patients with endometriosis-related pain treated with dienogest: a comparative study.

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.

[Metabolic features of the inflammatory syndrome of chronic pelvic pain (category IIIA of chronic non-bacterial prostatitis) in young men, depending on the somatotype].

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.

Effect of neurogenic acupoint cupping on high sensitive C-reactive protein and pain perception in female chronic pelvic pain: A randomized controlled trial.

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.

Serum macrophage migration inhibition factor for diagnosing endometriosis and its severity: case-control study.

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 potentialities of oxytocin receptor inhibitors for endometriosis therapy.

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 mm2 and 22.2 ± 1.2 mm2, 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.

Short-term benefits of balneotherapy for patients with chronic pelvic pain: a pilot study in Korea.

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 statementWhat 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.

Vaginal Diazepam for Nonrelaxing Pelvic Floor Dysfunction: The Pharmacokinetic Profile.

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 (Cmax) of 31.0 ng/mL was detected at a mean time (Tmax) 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.

Comparison of the clinical characteristics of patients with varicocele according to the presence or absence of scrotal pain.

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.

Establishment of experimental autoimmune prostatitis model by T2 peptide in aluminium hydroxide adjuvant.

A mouse model was developed to simulate the clinical features of chronic prostatitis/chronic pelvic pain syndrome using peptide (T2 ). Forty C57BL/6 mice were divided into four groups of 10 mice each, averagely and randomly. T2 plus aluminium hydroxide adjuvant group was given subcutaneous injection with the emulsion mixture of T2 and aluminium hydroxide adjuvant, the T2 group with T2 , 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-1ßin 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 T2 plus aluminium hydroxide adjuvant. Plasma levels of TNF-α and CRP were statistically elevated compared with control groups. The expression levels of IL-1ß in the prostate were more obvious than control groups. T2 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.

Assessment of biomarkers in women with endometriosis-associated pain using the ENG contraceptive implant or the 52 mg LNG-IUS: a non-inferiority randomised clinical trial.

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.

Therapeutic effects of Qian-Yu decoction and its three extracts on carrageenan-induced chronic prostatitis/chronic pelvic pain syndrome in rats.

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-1ß), 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-1ß (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.

[Histamine metabolism disorder in pathogenesis of chronic pelvic pain in patients with external genital endometriosis].

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 ЕLISA¼ 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.

Testosterone and Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Propensity Score-Matched Analysis.

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.

High-sensitive C-Reactive Protein as a Marker for Inflammation in Irritable Bowel Syndrome.

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.

Diagnosis of endometriosis in women with chronic pelvic pain.

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.

Serum carcinogenic antigen (CA)-125 and CA 19-9 combining pain score in the diagnosis of pelvic endometriosis in infertile women.

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.

[Common TCM syndrome pattern of chronic pelvic pain syndrome relates to plasma substance p and beta endorphin].

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.