Mediators of the association between childhood trauma and pain sensitivity in adulthood: a Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network analysis.

ABSTRACT: Urologic chronic pelvic pain syndrome (UCPPS) is a complex, debilitating condition in which patients often report nonpelvic pain in addition to localized pelvic pain. Understanding differential predictors of pelvic pain only vs widespread pain may provide novel pathways for intervention. This study leveraged baseline data from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network's Symptom Pattern Study to investigate the impact of childhood sexual and nonsexual violent trauma on pelvic and nonpelvic pain sensitivity among adult patients with UCPPS, as well as potential mediators of this association. Study participants who met inclusion criteria for UCPPS completed questionnaires assessing childhood and recent trauma, affective distress, cognitive dysfunction, and generalized sensory sensitivity. Experimental pain sensitivity was also evaluated using standardized pressure pain applied to the pubic region and the arm. Bivariate analyses showed that childhood violent trauma was associated with more nonviolent childhood trauma, more recent trauma, poorer adult functioning, and greater pain sensitivity at the pubic region, but not pain sensitivity at the arm. Path analysis suggested that childhood violent trauma was indirectly associated with pain sensitivity at both sites and that this indirect association was primarily mediated by generalized sensory sensitivity. More experiences of recent trauma also contributed to these indirect effects. The findings suggest that, among participants with UCPPS, childhood violent trauma may be associated with heightened pain sensitivity to the extent that trauma history is associated with a subsequent increase in generalized sensory sensitivity.

Distribution of the positive UPOINT domain in patients with chronic prostatitis or chronic pelvic pain syndrome: A multicenter observational study.

OBJECTIVE: To determine the UPOINT-positive domain numbers and evaluate the significance of the sexual dysfunction domain in patients with chronic prostatitis or chronic pelvic pain (CP/CPPS) in Japan. METHODS: A total of 58 patients with CP/CPPS with moderate or greater symptoms were included. Symptom severity was determined by > 14 on the chronic prostatitis symptom index (CPSI). The main outcome was to confirm the number and distribution of the positive UPOINT domains in this group. As secondary outcomes, the correlation between positive domain numbers and CPSI scores was evaluated. We also examined whether the sexual dysfunction subdomain, as determined by the five-item international index of erectile function, could improve the correlation with symptom severity. RESULTS: The mean age was 48.6 ± 15.4 years, CPSI score 24.3 ± 6.1, and positive UPOINT domain number 2.4 ± 0.9. The distribution of each positive domain was 67.2% for urinary, 15.5% for psychosocial, 75.8% for organ-specific, 3.4% for infection, 5.1% for neurological/systemic conditions, and 75.8% for tenderness. Although the mean CPSI total scores tended to increase with an increasing number of positive UPOINT domains, a significant correlation was not observed (r = 0.134, p = 0.312). The sexual dysfunction domain was positive in 62.0% of the cases, but the correlation could not be improved. CONCLUSIONS: Urinary, organ specific, and tenderness domains were mainly observed in patients with CP/CPPS. When patients with moderate or grater CPSI scores are clinically evaluated, clinicians should recognize that the UPOINT-positive domain and CPSI score are clinically and pathologically different concepts. (250 words).

Central sensitization inventory in endometriosis.

ABSTRACT: A key clinical problem is identifying the patient with endometriosis whose pain is complicated by central nervous system sensitization, where conventional gynecologic treatment (eg, hormonal therapy or surgery) may not completely alleviate the pain. The Central Sensitization Inventory (CSI) is a questionnaire previously validated in the chronic pain population. The objective of this study was an exploratory proof-of-concept to identify a CSI cutoff in the endometriosis population to discriminate between individuals with significant central contributors (identified by central sensitivity syndromes [CSS]) to their pain compared to those without. We analyzed a prospective data registry at a tertiary referral center for endometriosis, and included subjects aged 18 to 50 years with endometriosis who were newly or re-referred to the center in 2018. The study sample consisted of 335 subjects with a mean age of 36.0 ± 7.0 years. An increasing number of CSS was significantly correlated with dysmenorrhea, deep dyspareunia, dyschezia, and chronic pelvic pain scores (P < 0.001), and with the CSI score (0-100) (r = 0.731, P < 0.001). Receiver operating characteristic analysis indicated that a CSI cutoff of 40 had a sensitivity of 78% (95% CI: 72.7%-84.6%) and a specificity of 80% (95% CI: 70.3%-84.5%) for identifying a patient with endometriosis with ≥3 CSS. In the group with CSI ≥ 40, 18% retrospectively self-reported pain nonresponsive to hormonal therapy and 40% self-reported daily pain, compared with 6% and 20% in the CSI < 40 group (P = 0.003 and 0.002, respectively). In conclusion, a CSI ≥ 40 may be a practical tool to help identify patients with endometriosis with pain contributors related to central nervous system sensitization.

Running biomechanics in football players with and without hip and groin pain. A cross-sectional analysis of 116 sub-elite players.

OBJECTIVE: Examine whether football players with hip and/or groin (hip/groin) pain have impaired running biomechanics when compared to pain-free players, analysing men and women independently. DESIGN: Cross-sectional. SETTING: Biomechanics laboratory. PARTICIPANTS: Seventy-eight (62 men, 16 women) football players with >6months of hip/groin pain and a positive flexion-adduction-internal rotation test and 38 (25 men, 13 women) asymptomatic players. MAIN OUTCOME MEASURES: Pelvis angles and hip, knee, and ankle joint angles and moments were analysed during the stance phase of overground running at 3-3.5 m⋅s-1. Continuous joint angle and moment data were compared between symptomatic and asymptomatic football players of the same sex using statistical parametric mapping. Joint moment impulses (area under the curve) were compared between groups using linear regression models. RESULTS: Symptomatic football players did not display significant differences in pelvis angles or lower-limb joint angles, moments, or moment impulses during the stance phase of running, when compared to asymptomatic players of the same sex. CONCLUSION: Our large sample of football players with hip/groin pain who were still participating in competitive sport displayed similar running biomechanics to asymptomatic players. Impaired running biomechanics might exist in people with worse hip/groin pain, warranting future investigation.

Symmetry in Paraspinal Muscles as a Predictor of the Development of Pregnancy-Related Low Back and Pelvic Pain: A Prospective Study.

OBJECTIVE: To determine the asymmetry in the paraspinal muscle before pregnancy and evaluate its association with pregnancy-associated lumbopelvic pain (LPP). METHODS: This was a prospective case-control study conducted from January 2017 and December 2018. A total of 171 subjects (mean age ± SD, 27.4 ± 5.8 years) were finally divided into the LBP group, PGP group, and no LPP group. Each subject was asked to follow a standardized clinical imaging protocol before the pregnancy. The area of muscles (multifidus, erector spinae, and psoas muscles) on the axial slice at mid-disc of L4 -L5 and L5 -S1 were segmented and then the cross-sectional area (CSA) of a particular muscle was measured by outlining the innermost fascial border surrounding each muscle. The mean value of F-CSA's ratio to T-CSA (F/T CSA) was used to determine whether the bilateral paraspinal muscle was asymmetrical. Total muscle CSA (T-CSA) represents the sum of CSA of interested three muscles. The signal intensity can distinguish fat and muscle tissue in a different range. Based on this, functional CSA (F-CSA), represented by fat-free area, was evaluated quantitively by excluding the signal of the deposits of intramuscular fat. Total muscle CSA (T-CSA), functional CSA (F-CSA), and the ratio of F-CSA to T-CSA (F/T CSA) were measured unilaterally and compared between groups. Logistic regression was performed to determine the risk factors for pregnancy-associated LPP. The Pearson correlation coefficient was performed to test the relationship between asymmetry in F/T-CSA and pain rating. RESULTS: A total of 124 subjects (72.5%) (28.5 ± 5.2 years) had LPP during pregnancy. Forty-eight (38.7%) individuals had low back pain (LBP) and 76 (61.3%) had pelvic girdle pain (PGP). Seventy-six women (44.4%) were determined to have asymmetry in paraspinal muscle according to the definition in this methods section. The duration of follow-up was 24 months postpartum. A total of 39 (31.5%) women unrecovered from LPP. F/T-CSA was significantly decreased for LBP in the PGP group than in the and control group (0.03 ± 0.02 vs 0.05 ± 0.03 vs 0.12 ± 0.05, P < 0.001). Meanwhile, significant differences were detected in both groups (all P < 0.001). In patients with LBP, the level of paraspinal asymmetry, represented by the difference in F/T-CSA, was positively correlated with pain scores (r = 0.52, P < 0.01). However, no statistically significant correlation between pain scores and paraspinal asymmetry was found in PGP (r = 0.42, P > 0.05). Asymmetry in the paraspinal muscle (adjusted OR = 1.5), LBP (adjusted OR = 1.6), LPP in a previous pregnancy (adjusted OR = 1.4), sick leave ≥90 days (adjusted OR = 1.2), and heavy labor (adjusted OR = 1.2) were risk factors for the unrecovered LPP during pregnancy. CONCLUSIONS: Asymmetrical muscular compositions could lead to abnormal biomechanics for the segmental motions. Lateral-directed physical training and stretching may help decrease the occurrence and severity of this condition.

Cross-organ sensitization between the prostate and bladder in an experimental rat model of lipopolysaccharide (LPS)-induced chronic pelvic pain syndrome.

BACKGROUND: The aim of the current study was to investigate the effects of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) on bladder function via prostate-to-bladder cross-sensitization in a rat model of lipopolysaccharide (LPS)-induced prostate inflammation. METHODS: Male rats were intraprostatically injected with LPS or saline, serving as control. Micturition parameters were examined in a metabolic cage 10 or 14 days later. Subsequently, to evaluate bladder function, cystometry was performed. Micturition cycles were induced by saline infusion and cholinergic and purinergic contractile responses were measured by intravenous injection with methacholine and ATP, respectively. Thereafter, the prostate and bladder were excised and assessed histopathologically for possible inflammatory changes. RESULTS: Metabolic cage experiments showed increased urinary frequency in rats with LPS-induced CP/CPPS. Cystometry showed a significant increase in the number of non-voiding contractions, longer voiding time and lower compliance in CP/CPPS animals compared to controls. Induction of CP/CPPS led to significantly reduced cholinergic and purinergic bladder contractile responses. Histopathological analysis demonstrated prostatic inflammation in CP/CPPS animals. There were no significant differences between the groups regarding the extent or the grade of bladder inflammation. Prostate weight was not significantly different between the groups. CONCLUSIONS: The present study shows that prostate-to-bladder cross-sensitization can be triggered by an infectious focus in the prostate, giving rise to bladder overactivity and alterations in both afferent and efferent signalling. Future studies are required to fully understand the underlying mechanisms.

Acyloxyacyl hydrolase is a host determinant of gut microbiome-mediated pelvic pain.

Dysbiosis of gut microbiota is associated with many pathologies, yet host factors modulating microbiota remain unclear. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating condition of chronic pelvic pain often with comorbid urinary dysfunction and anxiety/depression, and recent studies find fecal dysbiosis in patients with IC/BPS. We identified the locus encoding acyloxyacyl hydrolase, Aoah, as a modulator of pelvic pain severity in a murine IC/BPS model. AOAH-deficient mice spontaneously develop rodent correlates of pelvic pain, increased responses to induced pelvic pain models, voiding dysfunction, and anxious/depressive behaviors. Here, we report that AOAH-deficient mice exhibit dysbiosis of gastrointestinal (GI) microbiota. AOAH-deficient mice exhibit an enlarged cecum, a phenotype long associated with germ-free rodents, and a "leaky gut" phenotype. AOAH-deficient ceca showed altered gene expression consistent with inflammation, Wnt signaling, and urologic disease. 16S sequencing of stool revealed altered microbiota in AOAH-deficient mice, and GC-MS identified altered metabolomes. Cohousing AOAH-deficient mice with wild-type mice resulted in converged microbiota and altered predicted metagenomes. Cohousing also abrogated the pelvic pain phenotype of AOAH-deficient mice, which was corroborated by oral gavage of AOAH-deficient mice with stool slurry of wild-type mice. Converged microbiota also alleviated comorbid anxiety-like behavior in AOAH-deficient mice. Oral gavage of AOAH-deficient mice with anaerobes cultured from IC/BPS stool resulted in exacerbation of pelvic allodynia. Together, these data indicate that AOAH is a host determinant of normal gut microbiota, and dysbiosis associated with AOAH deficiency contributes to pelvic pain. These findings suggest that the gut microbiome is a potential therapeutic target for IC/BPS.

Imaging of Pelvic Venous Disorders (PeVD); Should Every Patient Get an MRI?

Pelvic venous disease (PeVD) is part of the broad differential diagnosis of chronic pelvic pain with a challenging diagnosis and clinical workup to identify those patients that are most likely to benefit from intervention. Ultrasound, MRI, CT, venography, and intravascular ultrasound can all provide information to aid in the diagnostic algorithm. The purpose of this article is to review imaging as a component of the outpatient workup of patients with chronic pelvic pain to guide appropriate understanding and use of imaging modalities to accurately identify patients suffering from PeVD. A favored approach is to begin with transabdominal sonography with selective use of MRI/MRV in specific patient populations.

Non-venous Pelvic Pain and Roles for Pelvic Floor PT or Pudendal Nerve Blocks.

Non-venous pelvic pain is a dilemma that can frustrate even the most patient of providers. Managing these conditions can be even more bewildering as they require a multidisciplinary approach in most cases. Diet and lifestyle modifications in addition to physical therapy, biofeedback, medications, surgery and integrative medicine modalities can be used alone or in combination to relieve symptoms and should be individualized after proper evaluation and diagnosis. Because most of these conditions are located in the area of pudendal nerve distribution, pudendal nerve blocks have been very successful in helping to control the pain symptoms and should be used judiciously. Here we discuss the common conditions and how physical therapy and pudendal nerve blocks play a significant role in treatment.

Clinical Presentation and Evaluation of Pelvic Venous Disorders in Women.

The term pelvic venous disorders (PeVD) describes a group of related clinical entities with overlapping clinical presentations that were previously characterized by separate imprecise syndromic terminology. The clinical manifestations of PeVD may variously include chronic pelvic pain; pelvic origin extrapelvic lower extremity and genital varices; lower extremity pain and swelling; and left flank pain and hematuria. This manuscript focuses on the primary manifestations of PeVD in women - chronic pelvic pain and pelvic origin lower extremity and vulvar varices - and will review the underlying pathophysiology and related complicating factors (such as maladaptive pain responses) to explain the variety of clinical presentations.

Ovarian Vein Embolization: How and When Should It Be Done?

Pelvic Venous Disease (PeVD) is characterized by pelvic varicosities and chronic pelvic pain, defined as noncyclic pelvic pain that persists for more than 6 months. Pain and discomfort related to PeVD typically worsen with upright positioning and occur more frequently in multiparous and premenopausal women. The most common cause of PeVD is pelvic venous insufficiency (PVI) due to incompetent valves. Noninvasive imaging modalities such as ultrasound, computed tomography, or magnetic resonance imaging, and invasive catheter-based venography can help characterize varicosities and venous insufficiency, supporting the diagnosis of PeVD. In patients with PeVD, ovarian and/or internal iliac vein embolization demonstrate excellent technical and clinical success rates with relatively low complication rates and should be considered as standard management, in conjunction with medical therapy. Appropriate diagnostic work-up and patient selection are important prior to any intervention for achieving therapeutic success, as multiparous women have a higher success rate compared to patients with dyspareunia after embolization therapy. Post-procedure follow-up is critical for assessing symptom improvement and need for repeat intervention. However, further research is needed to identify additional predictors of successful outcomes after embolization therapy. This article aims to provide an overview of patient selection, interventional technique, challenges, and outcomes of ovarian vein embolization.

The short-term efficacy of electrical pudendal nerve stimulation versus intravesical instillation for the urethral pain syndrome: a randomized clinical trial.

PURPOSE: Urethral pain syndrome is a chronic condition characterized by disturbing feeling or server pain sensed at the urethra without specific treatment. This double-center, two-arm controlled trial aimed to explore the efficacy of electrical pudendal nerve stimulation (EPNS) versus intravesical instillation (II) of heparin and alkalinized lidocaine for urethral pain syndrome (UPS). METHODS: Eighty eligible patients took three sessions of EPNS, or 1 session of II per week, for 6 consecutive weeks. The primary end point was the change of pelvic pain and urgency/frequency symptom (PUF) score from baseline to week 6. Secondary outcome measures included changes of visual analogue scale (VAS) score and three sub-score extracted from PUF score. RESULTS: The enrolled participants were all included in the intention-to-treat analyses, and baseline characteristics between the two groups were well balanced. The post-treatment PUF score decreased by 10.0 (7.00, 16.50) in the EPNS group, and by 7.0 (3.00, 10.00) in the II group. At the closure of treatment, the medians of changes in symptom score, bother score, pain-related score and VAS score were 6.50 (4.25, 10.00), 4.00 (2.00, 6.00), 6.00 (5.00, 8.00),4.50 (2.25, 6.00), respectively, in the EPNS group, and 4.00 (2.00, 7.00), 3.00 (1.00, 3.00), 3.00 (2.00, 6.00), 2.00 (1.00, 4.00), respectively, in the II group. All the between-group differences were statistically significant. CONCLUSION: Compared with the II, the EPNS results in superior pain control and better relief of lower urinary tract symptoms, and deserves further attention. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03671993).

Clinical investigation of fertility after uterine artery embolization.

BACKGROUND: Uterine artery embolization is an effective and safe technique for the treatment of uterine fibroids, but its use remains controversial for women who wish to procreate. OBJECTIVE: This study aimed to study the clinical, anatomic, and obstetrical results of uterine artery embolization in patients of childbearing age not eligible for myomectomy. STUDY DESIGN: This was a retrospective cohort study of 398 female patients under the age of 43 years who were treated by uterine artery embolization between 2003 and 2017 for symptomatic fibroids and/or adenomyosis. Uterine artery embolization was performed according to a standardized procedure (fertility-sparing uterine artery embolization technique), with ovarian protection in the event of dangerous utero-ovarian anastomosis. Magnetic resonance imaging and pelvic ultrasounds were performed before and after uterine artery embolization. RESULTS: The overall clinical success rate (ie, resolution of preembolization symptoms such as heavy menstrual bleeding, iron-deficiency anemia, pelvic pressure) was 91.2%, and there were no major complications. One year after uterine artery embolization, we observed a mean 73% reduction in myoma volume. A total of 108 patients (49.3%) presented with dangerous utero-ovarian anastomosis and 33 (14.5%) benefited from ovarian protection. In our group, there were 148 pregnancies and 109 live births; 74 children were born at term; 23 were born preterm, on average at 35.12±2.78 weeks. Including preterm births, the mean birthweight and birth length of the children were within normal limits. Restoration of uterine anatomy and ovarian protection were identified as the main predictive factors for obstetrical success. Restoration was also a major predictive factor for clinical success and was associated with a lower rate of miscarriage. CONCLUSION: This study provided detailed clinical and obstetrical outcomes for 398 female patients who underwent uterine artery embolization for fibroid treatment; it contributes to the identification of anatomic and technical factors that could have an impact on fertility after uterine artery embolization. Further controlled clinical trials are needed to confirm our findings and reevaluate this procedure's indications and limitations for women with a desire to procreate.

Endometriosis: Etiology, pathobiology, and therapeutic prospects.

Endometriosis is a common condition associated with infertility that causes chronic pain in many, but not all, women. It is defined by the presence of endometrial-like tissue outside the uterus. Although the cause and natural history of the disorder remain uncertain, hormonal, neurological, and immunological factors are all implicated in the mechanisms contributing to development of symptoms. Because definitive diagnosis requires surgery, there is often a long diagnostic delay after onset of symptoms. Current interventions for endometriosis have limited efficacy and unacceptable side effects/risks and are associated with high rates of symptom recurrence. Here, we review recent advances in our understanding of the etiology of endometriosis, discuss current diagnostic and treatment strategies, highlight current clinical trials, and consider how recent results offer new avenues for the identification of endometriosis biomarkers and the development of effective non-surgical therapies that are fertility-sparing.

Potential Alterations of Functional Connectivity Analysis in the Patients with Chronic Prostatitis/Chronic Pelvic Pain Syndrome.

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one of the most common diseases in urology, but its pathogenesis remains unclear. As a kind of chronic pain which the patients suffered for more than 3 months, we investigated the influence on patients' brain functional connectivity in resting state. Methods: We recruited a cohort of 18 right-handed male patients with CP/CPPS and 21 healthy male right-handed age-matched controls. Their resting-state fMRI data and structural MRI data were preprocessed and processed by RESTPlus V1.22. To assess the integrity of the default mode network (DMN), we utilized the voxel-wised analysis that we set medial prefrontal cortex (mPFC) and posterior cingulate gyrus (PCC) as seed points to compare the global functional connectivity (FC) strength. Results: Compared with healthy control, the FC strength between left mPFC and posterior DMN decreased in the group of CP/CPPS (P < 0.05, GFR correction, voxel P < 0.01, cluster P < 0.05), and the FC strength between the left anterior cerebellar lobe and posterior DMN increased (P < 0.05, GFR correction, voxel P < 0.01, cluster P < 0.05). In the patient group, there was a positive correlation between the increased FC strength and the score of the Hospital Anxiety and Depression Scale (HADS) anxiety subscale (r = 0.5509, P = 0.0178) in the left anterior cerebellar lobe, a negative correlation between the decreased FC strength and the score of the National Institutes of Health Chronic Prostatitis Symptom Index (r = -0.6281, P = 0.0053) in the area of left mPFC, and a negative correlation between the decreased FC strength and the score of HADS anxiety subscale (r = -0.5252, P = 0.0252). Conclusion: Patients with CP/CPPS had alterations in brain function, which consisted of the default mode network's compromised integrity. These alterations might play a crucial role in the pathogenesis and development of CP/CPPS.

Physiotherapeutic assessment and management of chronic pelvic pain syndrome: A case report.

INTRODUCTION: Chronic pelvic pain syndrome is difficult for the diagnosis and therapy and that means the patient attending the physician or physiotherapist may present various symptoms. There are no guidelines concern physiotherapy diagnosis and treatment of chronic pelvic pain syndrome. This study presents the physiotherapeutic assessment and management in men with pelvic pain symptoms. PATIENT CONCERNS: Forty-six-year-old man attended the physiotherapy consulting room due to symptoms of pain in the perineum, lower abdomen, urethra, and scrotum for a year. Earlier, the patient had consulted a urologist who made a diagnosis of cystitis and prescribed medications that did not get results. DIAGNOSIS: Ultrasound imaging and manual inspection (per rectum) of the pelvic floor was conducted by physiotherapist. Also, the abdominal and lower extremities muscles were assessed. Patient reported pain symptoms during examination of the musculus ischiocavernosus, puboanalis, pubococcygeus, iliococcygeus, coccygeus, and canalis pudentalis seu Alcocki. INTERVENTIONS: The patient was given physiotherapeutic interventions consisting in the manual therapy of the lumbopelvic hip complex and the manual therapy per rectum. OUTCOMES: During 10th session of the physiotherapeutic treatment, patient reported improvement in pain symptoms. A month later, patient reported total alleviation of the pain symptoms during control visit. CONCLUSION: Therapy of chronic pelvic pain syndrome is a process that involves application of different therapies and different approaches. Functional and structural assessment and also therapy conducted by physiotherapist is becoming an integral part of urology and represents 1 possible conservative treatment form.

Estradiol/nomegestrol acetate as a first-line and rescue therapy for the treatment of ovarian and deep infiltrating endometriosis.

PURPOSE: Estradiol valerate/nomegestrol acetate (E2V/NOMAC) is a new combined oral contraceptive with a good tolerability profile and low drop-out rates, which was shown to improve menstrual-related symptoms. This study aims to evaluate its effectiveness in the control of symptoms and progression of disease in women with ovarian endomestriomas and deep infiltrating endometriosis (DIE). METHODS: This was a retrospective cohort study on 39 women with pelvic endometriosis treated with E2V/NOMAC. We assessed for each patient, at the beginning of treatment and after 6 months, the painful symptoms, through a global VAS (Visual Analogue Scale) index and the size of the greatest ovarian and/or deep infiltrating endometriotic lesions. RESULTS: After 6 months of treatment, a significant reduction was observed for the global VAS score for pain symptoms and for the mean size of ovarian endometriomas, whereas DIE lesions did not present significant changes in mean size. CONCLUSIONS: E2/NOMAC was effective in reducing pain symptoms associated with pelvic endometriosis and the size of ovarian endometriomas, whereas DIE lesions remained stable. This therapy could provide good results in the control of symptoms and disease progression in women with pelvic endometriosis.

Is primary dysmenorrhea a precursor of future endometriosis development?

Primary dysmenorrhea (PD) is the most common gynecologic disorder during adolescence and it is characterized by crampy lower abdominal pain that occurs during menstruation. Secondary dysmenorrhea, in contrast, has the same clinical features but occurs in women with a disease that could account for their symptoms (endometriosis, adenomyosis, uterine fibroids, pelvic inflammatory disease). Endometriosis is the most common cause of secondary dysmenorrhea and it should be considered in patients with persistent and clinically significant dysmenorrhea despite treatment. It is often diagnosed after a long delay, increasing the likelihood of pain chronicity and fertility problems at a later age. Women who suffer from dysmenorrhea in adolescence have higher risk of endometriosis in future. The open question is if endometriosis was already present at the onset of dysmenorrhea but undiagnosed or if PD favors subsequent development of endometriosis-associated pain. Since PD is associated with higher risk for developing chronic pain state and shares some of the same pain pathways of endometriosis (prostaglandins overproduction, inflammation, peripheral sensitization, central sensitization and abnormal stress responses), a correlation between PD and endometriosis is suggested. To know whether it is a risk factor for the development of endometriosis-associated pain may provide an opportunity for early intervention and prevention. The present review aims to investigate the clinical and pathogenetic features of PD and endometriosis in order to identify a possible association between the two conditions.

The effect of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis.

BACKGROUND: To our knowledge, data on the effects of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis are limited. This study was conducted to determine the effects of vitamin D supplementation on clinical symptoms and metabolic profiles in patients with endometriosis. METHODS: The current randomized, double-blind, placebo-controlled trial was conducted among 60 patients (aged 18-40 years old) with endometriosis. Participants were randomly allocated into two groups (30 participants each group) to receive either 50,000 IU vitamin D or placebo each 2 weeks for 12 weeks. RESULTS: Vitamin D supplementation significantly decreased pelvic pain (ß - 1.12; 95% CI, -2.1, -0.09; p=.03) and total-/HDL-cholesterol ratio (ß - 0.29; 95% CI, -0.57, -0.008; p=.04) compared with the placebo. Moreover, vitamin D intake led to a significant reduction in high-sensitivity C-reactive protein (hs-CRP) (ß - 0.64 mg/L; 95% CI, -0.97, -0.30; p<.001) and a significant increase in total antioxidant capacity (TAC) (ß 47.54 mmol/L; 95% CI, 19.98, 75.11; p=.001) compared with the placebo. CONCLUSIONS: Overall, our study demonstrated that vitamin D intake in patients with endometriosis resulted in a significant improvement of pelvic pain, total-/HDL-cholesterol ratio, hs-CRP and TAC levels, but did not affect other clinical symptoms and metabolic profiles.

Prostate-to-bladder cross-sensitization in a model of zymosan-induced chronic pelvic pain syndrome in rats.

BACKGROUND: The aim of the present study was to investigate the effects of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) on bladder function and pathophysiology. METHODS: To create a model for CPPS, rats were intraprostatically injected with zymosan or saline, serving as control. Metabolic cage experiments were performed 7, 14, or 21 days after zymosan injection and after 14 days in the control group. Thereafter, cystometry was performed in which simulated micturition cycles were induced by saline infusion and contractile responses to the cholinergic agonist methacholine and the purinergic agonist ATP were measured. Following cystometry, the prostate and urinary bladder were excised and assessed histopathologically for possible inflammatory changes. RESULTS: Metabolic cage data revealed a significantly increased urinary frequency in zymosan treated rats. Likewise, the volume per micturition was significantly lower in all CPPS groups compared to controls. Cystometry showed a significant increase in the number of nonvoiding contractions, longer voiding time, and a trend towards lower compliance in CPPS rats compared to controls. Induction of CPPS led to significantly reduced cholinergic and purinergic contractile responses. Histopathological analysis demonstrated prostatic inflammation in all CPPS groups, in particular in later stage groups. Both the extent and grade of bladder inflammation were significantly higher in CPPS groups compared to controls. CONCLUSIONS: The current findings demonstrate a potential prostate-to-bladder cross-sensitization leading to symptoms of bladder overactivity and signs of bladder inflammation. Future clinical studies are required to verify the outcomes of the current study and enable advancement of patient care.