Reduced concentrations of vaginal metabolites involved in steroid hormone biosynthesis are associated with increased vulvar vestibular pain and vaginal muscle tenderness in provoked vestibulodynia: An exploratory metabolomics study.

Provoked vestibulodynia (PVD) is a chronic vulvar pain disorder characterized by hypersensitivity and severe pain with pressure localized to the vulvar vestibule. Knowledge regarding pathophysiological mechanisms contributing to the etiology and production of symptoms in PVD remains incomplete but is considered multifactorial. Using a cross-sectional observational study design, data from untargeted metabolomic profiling of vaginal fluid and plasma in women with PVD and healthy women was combined with pain testing and brain imaging in women with PVD to test the hypotheses that women with PVD compared to healthy women show differences in vaginal and plasma metabolites involved in steroid hormone biosynthesis. Steroid hormone metabolites showing group differences were correlated with vulvar vestibular pain and vaginal muscle tenderness and functional connectivity of brain regions involved in pain processing in women with PVD to provide insight into the functional mechanisms linked to the identified alterations. Sensitivity analyses were also performed to determine the impact of hormonal contraceptive use on the study findings. Women with PVD compared to healthy controls had significant reductions primarily in vaginal fluid concentrations of androgenic, pregnenolone and progestin metabolites involved in steroidogenesis, suggesting localized rather than systemic effects in vagina and vulvar vestibule. The observed reductions in androgenic metabolite levels showed large effect size associations with increased vulvar vestibular pain and vulvar muscle tenderness and decreases in androgenic and progestin metabolites were associated with decreased connectivity strength in primary sensorimotor cortices. Women with PVD showed symptom-associated reductions in vaginal fluid concentrations of metabolites involved in the biosynthesis of steroid hormones previously shown to affect the integrity of vulvar and vaginal tissue and nociceptive processing. Deficiency of certain steroids may be an important mechanism contributing to the pathophysiology of symptoms in PVD may provide potential diagnostic markers that could lead to new targets for therapeutic intervention.

Dysregulation in Sphingolipid Signaling Pathways is Associated With Symptoms and Functional Connectivity of Pain Processing Brain Regions in Provoked Vestibulodynia.

Provoked vestibulodynia (PVD) is a chronic pain disorder characterized by local hypersensitivity and severe pain with pressure localized to the vulvar vestibule. Despite decades of study, the lack of identified biomarkers has slowed the development of effective therapies. The primary aim of this study was to use metabolomics to identify novel biochemical mechanisms in vagina and blood underlying brain biomarkers and symptoms in PVD, thereby closing this knowledge gap. Using a cross-sectional case-control observational study design, untargeted and unbiased metabolomic profiling of vaginal fluid and plasma was performed in women with PVD compared to healthy controls. In women with PVD, we also obtained assessments of vulvar pain, vestibular and vaginal muscle tenderness, and 24-hour symptom intensity alongside resting-state brain functional connectivity of brain regions involved in pain processing and modulation. Compared to healthy controls, women with PVD demonstrated differences primarily in vaginal (but not plasma) concentrations of metabolites of the sphingolipid signaling pathways, suggesting localized effects in vagina and vulvar vestibule rather than systemic effects. Our findings reveal that dysregulation of sphingolipid metabolism in PVD is associated with increased vulvar pain and muscle tenderness, sexual dysfunction, and decreased functional connectivity strength in pain processing/modulatory brain regions. This data collectively suggests that alterations in sphingolipid signaling pathways are likely an important molecular biomarker in PVD that could lead to new targets for therapeutic intervention. PERSPECTIVE: This manuscript presents the results of a robust, unbiased molecular assessment of plasma and vaginal fluid samples in women with provoked vestibulodynia compared to healthy controls. The findings suggest that alterations in sphingolipid signaling pathways are associated with symptoms and brain biomarkers and may be an important molecular marker that could provide new targets for therapeutic intervention.

The Tissue Renin-Angiotensin System and Its Role in the Pathogenesis of Major Human Diseases: Quo Vadis?

Evidence has arisen in recent years suggesting that a tissue renin-angiotensin system (tRAS) is involved in the progression of various human diseases. This system contains two regulatory pathways: a pathological pro-inflammatory pathway containing the Angiotensin Converting Enzyme (ACE)/Angiotensin II (AngII)/Angiotensin II receptor type 1 (AGTR1) axis and a protective anti-inflammatory pathway involving the Angiotensin II receptor type 2 (AGTR2)/ACE2/Ang1-7/MasReceptor axis. Numerous studies reported the positive effects of pathologic tRAS pathway inhibition and protective tRAS pathway stimulation on the treatment of cardiovascular, inflammatory, and autoimmune disease and the progression of neuropathic pain. Cell senescence and aging are known to be related to RAS pathways. Further, this system directly interacts with SARS-CoV 2 and seems to be an important target of interest in the COVID-19 pandemic. This review focuses on the involvement of tRAS in the progression of the mentioned diseases from an interdisciplinary clinical perspective and highlights therapeutic strategies that might be of major clinical importance in the future.

Multimodal physical therapy versus topical lidocaine for provoked vestibulodynia: a multicenter, randomized trial.

BACKGROUND: Provoked vestibulodynia is the most common subtype of chronic vulvar pain. This highly prevalent and debilitating condition is characterized by acute recurrent pain located at the entry of the vagina in response to pressure application or attempted vaginal penetration. Although physical therapy is advocated as a first-line treatment for provoked vestibulodynia, evidence supporting its efficacy is scarce. OBJECTIVE: The purpose of this study was to establish the efficacy of multimodal physical therapy compared with topical lidocaine, a frequently used first-line treatment. STUDY DESIGN: We conducted a multicenter, parallel-group, randomized clinical trial in women diagnosed as having provoked vestibulodynia recruited from the community and 4 Canadian university hospitals. Women were randomly assigned (1:1) to receive either weekly sessions of physical therapy or overnight topical lidocaine (5% ointment) for 10 weeks. Randomization was stratified by center using random permuted blocks from a computer-generated list managed by an independent individual. Physical therapy entailed education, pelvic floor muscle exercises with biofeedback, manual therapy, and dilation. Assessments were conducted at baseline, posttreatment, and 6-month follow-up. Outcome assessors, investigators, and data analysts were masked to allocation. The primary outcome was pain intensity during intercourse evaluated with the numeric rating scale (0-10). Secondary outcomes included pain quality (McGill-Melzack Pain Questionnaire), sexual function (Female Sexual Function Index), sexual distress (Female Sexual Distress Scale), satisfaction (numeric rating scale of 0-10), and participants' impression of change (Patient Global Impression of Change). Intention-to-treat analyses were conducted using piecewise linear-growth models. RESULTS: Among 212 women who were recruited and randomized, 201 (95%) completed the posttreatment assessment and 195 (92%) completed the 6-month follow-up. Multimodal physical therapy was more effective than lidocaine for reducing pain intensity during intercourse (between-group pre-post slope difference, P<.001; mean group postdifference, 1.8; 95% confidence interval, 1.2-2.3), and results were maintained at 6-month follow-up (mean group difference, 1.8; 95% confidence interval, 1.2-2.5). The physical therapy group also performed better than the lidocaine group in all secondary outcomes (pain quality, sexual function, sexual distress, satisfaction, and participants' impression of change) at posttreatment and 6-month follow-up. Moreover, the changes observed after physical therapy were shown to be clinically meaningful. Regarding participants' impression of change, 79% of women in the physical therapy group reported being very much or much improved compared with 39% in the lidocaine group (P<.001). CONCLUSION: The findings provide strong evidence that physical therapy is effective for pain, sexual function, and sexual distress and support its recommendation as the first-line treatment of choice for provoked vestibulodynia.

Vulvodynia.

Vulvodynia is a condition that occurs in 8-10% of women of all ages and is characterized by pain at the vulva that is present during sexual and/or non-sexual situations. Diagnosis is established through careful medical history and pelvic examination, including the cotton-swab test. The onset and maintenance of vulvodynia involves a complex interplay of peripheral and central pain mechanisms, pelvic floor muscle and autonomic dysfunction, anxiety, depression and childhood maltreatment as well as cognitive-affective, behavioural and interpersonal factors. Given the absence of empirically supported treatment guidelines, a stepwise approach of pelvic floor physical therapy and cognitive behavioural therapy as well as medical management is suggested, with surgery as the last option. Vulvodynia has a negative effect on the quality of life of women and their partners, and imposes a profound personal and societal economic burden. In addition, women with vulvodynia are more likely to report other chronic pain conditions, which further alters their quality of life. Future efforts should aim to increase girls', women's and healthcare professionals' education and awareness of vulvodynia, phenotype different subgroups of women based on biopsychosocial characteristics among more diverse samples, conduct longitudinal studies and improve clinical trial designs.

Pain Trajectories and Predictors: A 7-Year Longitudinal Study of Women With Vulvodynia.

INTRODUCTION: A significant proportion of women report a reduction of symptoms over time-even without treatment-yet the natural progression of vulvodynia and which factors may explain decrease vs persistence of pain remain unclear. AIM: To identify subgroups of pain trajectories in women with vulvodynia and to predict these different trajectories by treatments undertaken, pain characteristics, and psychosocial factors. METHODS: Data on pain intensity, treatments undertaken, pain characteristics, and psychosocial factors were collected 3 times over a 7-year period from 173 women who screened positive for vulvodynia. Latent class growth analysis was conducted to identify homogeneous subgroups with distinct pain trajectories. A multivariate binomial logistic regression was used to examine whether treatments, pain characteristics, and psychosocial factors predicted these trajectories. MAIN OUTCOME MEASURE: The main outcome was pain intensity (0-10), measured at 3 time points with the numerical rating scale. RESULTS: 2 pain trajectories were identified: 1 where pain persisted (28.9%), and 1 where pain decreased over time (71.1%). Whether a treatment had been undertaken was not predictive of the course of pain over time. Women who were older at first pain onset, had pain at another location than the entrance of the vagina, and reported more anxiety were more likely to have a persistent pain trajectory relative to the decreased pain trajectory. CLINICAL IMPLICATIONS: Findings suggest that the evolution of pain differs among women with vulvodynia depending on pain characteristics and anxiety. STRENGTHS & LIMITATIONS: Strengths of the study include the 7-year longitudinal design to examine the natural history of provoked vestibulodynia and the inclusion of biopsychosocial factors as predictors of pain trajectories. However, women with major medical and psychiatric illnesses or deep dyspareunia were not included, and, thus, these factors could not be examined as predictors. CONCLUSION: Assessing baseline characteristics associated with different pain trajectories during medical visits could have positive implications for the management of vulvodynia. Pâquet M, Vaillancourt-Morel M-P, Jodouin J-F, et al. Pain Trajectories and Predictors: A 7-Year Longitudinal Study of Women With Vulvodynia. J Sex Med 2019;16:1606-1614.

Motor Function and Perception of Health in Women with Provoked Vestibulodynia.

BACKGROUND: Provoked vestibulodynia (PVD) is a prevalent and disabling condition in women that may be associated with reduced quality of life and impairment of physical functioning. AIM: To investigate whether women with PVD have different motor functions, posture and breathing patterns, and whether they perceive their physical health differently, compared with asymptomatic controls. METHODS AND MAIN OUTCOME MEASURE: The Standardized Mensendieck Test (SMT) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) were used to assess differences between 35 women with PVD and 35 healthy controls. RESULTS: There were no statistically significant differences in any of the 5 motor domains of the SMT between the women with PVD and those without PVD: standing posture, 4.0 (0.6) vs 5.0 (0.6); gait, 4.7 (0.6) vs 4.8 (0.6); movement, 4.8 (0.8) vs 5.1 (0.6); sitting posture, 4.7 (1.0) vs 4.9 (0.8); respiration, 4.7 (1.0) vs 4.7 (0.9). Women with PVD scored significantly lower in all domains on the SF-36 (adjusted Bonferroni P = .002) except physical functioning. CLINICAL IMPLICATIONS: Given the lack of difference in the SF-36 physical functioning domain and in all 5 domains of the SMT between women with PVD and those without PVD, the value of interventions focusing on general physical function is unclear. STRENGTHS & LIMITATIONS: A study strength is the use of an assessor-blinded case-control design, trained physiotherapists to conduct the tests, and valid and reliable outcome measures. A limitation is the homogeneity of the sample of young nulliparous women, which limits the generalizability of our findings to other study populations. CONCLUSION: Young nulliparous women with PVD did not score differently from a group of healthy controls on assessment of overall physical functioning or on standing posture, gait, movement, sitting posture, and respiration. However, the score for perception of general health was lower in the women with PVD compared with controls. I. Næss, H.C. Frawley, K. Bø. Motor Function and Perception of Health in Women with Provoked Vestibulodynia. J Sex Med 2019;16:1060-1067.

Tetrahydrocannabinol Reduces Hapten-Driven Mast Cell Accumulation and Persistent Tactile Sensitivity in Mouse Model of Allergen-Provoked Localized Vulvodynia.

Vulvodynia is a remarkably prevalent chronic pain condition of unknown etiology. An increase in numbers of vulvar mast cells often accompanies a clinical diagnosis of vulvodynia and a history of allergies amplifies the risk of developing this condition. We previously showed that repeated exposures to oxazolone dissolved in ethanol on the labiar skin of mice led to persistent genital sensitivity to pressure and a sustained increase in labiar mast cells. Here we sensitized female mice to the hapten dinitrofluorobenzene (DNFB) dissolved in saline on their flanks, and subsequently challenged them with the same hapten or saline vehicle alone for ten consecutive days either on labiar skin or in the vaginal canal. We evaluated tactile ano-genital sensitivity, and tissue inflammation at serial timepoints. DNFB-challenged mice developed significant, persistent tactile sensitivity. Allergic sites showed mast cell accumulation, infiltration of resident memory CD8+CD103+ T cells, early, localized increases in eosinophils and neutrophils, and sustained elevation of serum Immunoglobulin E (IgE). Therapeutic intra-vaginal administration of Δ9-tetrahydrocannabinol (THC) reduced mast cell accumulation and tactile sensitivity. Mast cell-targeted therapeutic strategies may therefore provide new ways to manage and treat vulvar pain potentially instigated by repeated allergenic exposures.

Gynecological associated disorders and management.

BACKGROUND: Chronic pelvic pain syndrome is complex and involves multiple organ systems. The gynecological aspects of chronic pelvic pain syndrome can be divided into four different areas: intra-abdominal, vaginal, pelvic floor muscles and sexual pain. This article provides an overview of gynecological evaluation in patients with chronic pelvic pain and reviews the most common gynecological diagnoses and their management. METHODS: An extensive review of the literature including guidelines from the International Continence Society, the European Association of Urology, and the International Association for the Study of Pain was performed. RESULTS: Gynecological evaluation of patients with chronic pelvic pain begins with a thorough history and physical examination. Laboratory tests, imaging studies and diagnostic procedures can be used as adjuncts to make a diagnosis. Treatment modalities include physical therapy, medications, trigger points injections, and surgery. CONCLUSION: Common gynecological diagnoses of chronic pelvic pain include endometriosis, adenomyosis, vulvodynia, high tone pelvic floor dysfunction, and genitopelvic pain/penetration disorder. Gynecology is one of the many systems that can be associated with chronic pelvic pain. Managing patients with chronic pelvic pain requires a multimodal and multidisciplinary approach.

Vulval Pain in Pediatric and Adolescent Patients.

STUDY OBJECTIVE: To describe the experience of a tertiary pediatric and adolescent gynecology service that provides care to children and adolescents who present with vulval pain. Their presentation, associated symptoms, and management is described. DESIGN: A retrospective analysis of all girls younger than 18 years of age who presented to the gynecology clinic of our tertiary referral Children's Hospital between Jan 2010 and July 2016. Electronic medical records were reviewed and parameters recorded using a standardized data sheet. SETTING: Gynecology clinic of a tertiary referral children's hospital and private rooms of our director of gynecology. PARTICIPANTS: Young women younger than 18 years who presented with symptoms suggestive of vulvodynia. INTERVENTIONS AND MAIN OUTCOME MEASURES: Presenting symptoms, characteristics of associated features, treatment options, and treatment outcomes. RESULTS: Forty-seven patients with a mean age of 11 years (range, 3-18 years) were identified. At the time of diagnosis 31/47 (65.9%) were premenarchal. Many presented with a symptom other than pain alone. In particular, 35/47 (74.4%) presented with coexisting or previous urinary symptoms. Of patients examined, most had positive cotton tip examination findings (16/17 (94.1%) and 11/13 (84.6%) for pre- and postmenarchal, respectively) with clinical inspection otherwise unremarkable. CONCLUSION: Children and adolescents with vulval pain have varied presentations. Many of the pre- and postmenarchal patients had coexisting urinary tract symptomatology at the time of diagnosis. This review of patients seen over 5.5 years at a pediatric tertiary referral center provides information on the presenting symptoms, examination features, and response to clinical management.

Interpersonal trauma and aging-related genitourinary dysfunction in a national sample of older women.

BACKGROUND: Among reproductive-aged women, exposure to interpersonal trauma is associated with genitourinary symptoms. Little is known about the relationship between these exposures and the genitourinary health of older women, who tend to experience different and more prevalent genitourinary symptoms because of menopause and aging. OBJECTIVES: In this study, we examined relationships between common types of interpersonal trauma and aging-related genitourinary dysfunction among older women. STUDY DESIGN: We analyzed data from the National Social Life, Health, and Aging Project, a national area probability sample of older community-dwelling adults born between 1920 and 1947. We used cross-sectional data from home-based study visits conducted in 2005-2006 to examine interpersonal violence exposures (any lifetime sexual assault, past-year emotional and physical abuse), and past-year genitourinary symptoms (urinary incontinence, other urinary problems, and vaginal pain/lubrication problems with sexual intercourse) among women participants. Multivariable logistic regression models were used to relate interpersonal violence and genitourinary symptoms, adjusting for age, race/ethnicity, body mass index, education, marital status, parity, hormone therapy, depressive and anxiety symptoms, and self-reported health. In exploratory models, we further adjusted for vaginal maturation, a tissue-specific marker of aging-related urogenital atrophy obtained from vaginal self-swabs. RESULTS: In this national sample of 1551 older women (mean age 69 ± 2 years), 9% reported sexual assault, 23% reported emotional abuse, and <1% reported physical abuse. Urinary incontinence and other urinary problems were reported by 42% and 17%, respectively, and 42% of sexually active women (n = 527) reported vaginal symptoms with intercourse. In multivariable regression analyses adjusted for age, race/ethnicity, education, marital status, parity, hormone therapy, anxiety, depressive symptoms, and self-reported health, women with any lifetime history of sexual assault had 2.5 times the odds (95% confidence interval, 1.0-6.3) of vaginal symptoms, while women who reported past-year emotional abuse had higher odds of urinary incontinence (odds ratio, 1.7, 95% confidence interval, 1.2-2.4) and other urinary problems (odds ratio, 1.8, 95% confidence interval, 1.2-2.8). Among women who provided vaginal self-swabs (n = 869), adjustment for vaginal maturation-attenuated associations with other urinary problems (odds ratio, 1.6, 95% confidence interval, .9-2.6) and vaginal symptoms (odds ratio, 2.2, 95% confidence interval, 0.8-5.8). CONCLUSION: Sexual assault and emotional abuse may play a role in the development or experience of aging-related genitourinary dysfunction in older women. Clinicians caring for older women should recognize the prevalence and importance of traumatic exposures in health related to menopause and aging.

Reliability of vulvar blood perfusion in women with provoked vestibulodynia using laser Doppler perfusion imaging and laser speckle imaging.

BACKGROUND: Microvascular assessment has become increasingly used in gynecology to better understand the pathophysiology of various vulvar conditions and to study sexual function. Alteration in blood perfusion of the vulvar area has been observed using laser technologies in women with provoked vestibulodynia (PVD), the leading cause of vulvar pain. However, no studies have thus far investigated the reliability of and agreement between lasers for evaluating vulvar blood perfusion. OBJECTIVES: The main objective was to investigate the between-session reliability of the laser Doppler perfusion imaging (LDPI) and laser speckle contrast imaging (LSCI) for assessing blood perfusion of the vulvar vestibule in women with PVD. Secondary aims were to evaluate the association and agreement between the two laser technologies. METHODS: Twenty-six women with PVD participated in the study. Blood perfusion of the vulvar vestibule was assessed with LDPI and LSCI during two sessions 2 to 4 weeks apart. Blood perfusion was analyzed in five specific areas of the vulvar vestibule: 1) 3 o'clock site, 2) 6 o'clock site, 3) 9 o'clock site, 4) central area (delimited by areas 1, 2 and 3), and 5) posterior fourchette. The reliability of the measurements of the two instruments was calculated with intraclass correlation coefficients (ICCs), standard errors of measurement (SEMs) and coefficients of variation (CVs). Paired t-tests were also computed to compare the CVs of each laser technology. The association and agreement between LDPI and LSCI measurements were evaluated by Pearson's correlation coefficients and Bland-Altman plots, respectively. RESULTS: Excellent reliability was found for LDPI (ICCs = 0.78-0.80, p < 0.001, SEMs = 16.1-47.9) and LSCI measurements (ICCs = 0.75-0.81, p ≤ 0.001, SEMs = 17.0-52.2) for all vulvar vestibule areas. However, CVs were significantly higher using LDPI (CVs = 15.1-19.8) when compared to LSCI (CVs = 7.0-11.6) for all areas (p ≤ 0.031), except for area 4 (p = 0.079). Significant correlations were found between LDPI and LSCI for all areas (r = 0.58-0.89, p ≤ 0.003). Bland-Altman plots revealed a systematic difference between LDPI and LSCI measurements. CONCLUSION: Findings show that both LDPI and LSCI measurements are reliable for assessing blood perfusion of the vulvar vestibule in women with PVD. The LSCI appears to be a more reliable measurement as it presents less variation than LDPI. Finally, although LDPI and LSCI measurements are related, the systematic difference observed between them makes it impossible to compare absolute units.

The Relationship Between Vulvovaginal Candidiasis and Provoked Vulvodynia: A Systematic Review.

BACKGROUND: Provoked vulvodynia (PVD) is a chronic vulvar pain condition affecting up to 8.3% of the female population. Despite many years of research, no clear cause for PVD has been identified. Several risk factors have been studied, including vulvovaginal candidiasis (VVC). However, to date, the role of Candida infections in PVD has remained unclear. VVC and PVD have an overlap of symptoms that may contribute to diagnostic inaccuracy and mistreatment. AIM: To systematically review the literature on the relationship between VVC and PVD. METHODS: Cohort and case-control studies were included that compared women with PVD with healthy controls with respect to the presence of a history of Candida vulvovaginitis. PVD had to be diagnosed by Friedrich's criteria or the International Society for the Study of Vulvovaginal Disease criteria. The inclusion process as well as the quality appraisal of the studies, using the Newcastle-Ottawa Quality Assessment Scale, were performed independently by 2 authors. MAIN OUTCOME MEASURE: Outcomes of the population-based case-control studies were listed as odds ratio. Outcomes of the pathophysiological studies were based on local pro-inflammatory responses on Candida in vitro. RESULTS: We included a total of 14 studies, both population and clinic-based case-control, and pathophysiological research. 7 studies were of low methodological quality, and 7 studies were of medium methodological quality. The population-based case-control studies showed a significantly increased odds ratio for self-reported VVC in PVD cases compared with controls. The pathophysiological studies revealed a tendency for an increased local proinflammatory response on Candida in vitro in patients with PVD. Owing to the substantial heterogeneity of the studies, meta-analysis was not performed. CLINICAL IMPLICATIONS: Health care providers may consider a diagnosis of PVD in women with self-reported VVC, and to act on this properly. Reiteration of antifungal prescriptions by physicians without a decent diagnosis, will lead to mistreatment. Women should be informed by their health care provider that intercourse during (or shortly after) the treatment of VVC might worsen the vulnerability of the vulvar skin. STRENGTH AND LIMITATIONS: This is the first systematic review performed to describe the relation between VVC and PVD. An independently performed in- and exclusion process and quality appraisal, ensured optimal internal validity. However, there were important methodological limitations and the size of heterogeneity prevented establishing a meta-analysis. CONCLUSION: This systematic review is unable to draw conclusions regarding a relationship between actual VVC and PVD because studies were based on self-reported VVC. Until new evidence becomes available, we advocate that PVD should be considered as an unexplained chronic pain condition. In women with recurrent or persistent VVC-like complaints, physicians should consider a diagnosis of PVD. Leusink P, van de Pasch S, Teunissen D, et al. The Relationship Between Vulvovaginal Candidiasis and Provoked Vulvodynia: A Systematic Review. J Sex Med 2018;15:1310-1321.

Pelvic Floor Muscle Morphometry and Function in Women With Primary and Secondary Provoked Vestibulodynia.

INTRODUCTION: Provoked vestibulodynia (PVD) can be categorized as primary PVD affecting women from their first sexual intercourse or secondary PVD, which appears after a period of pain-free intercourse. There is growing evidence that these subgroups may be distinct entities presenting different pathophysiological mechanisms. Although there are documented pelvic floor muscle alterations in provoked vestibulodynia, no study has yet evaluated whether the pelvic floor muscle morphometry or function differed between women with primary and secondary provoked vestibulodynia. AIM: To assess and compare pelvic floor muscle morphometry and function in women with primary and secondary provoked vestibulodynia. METHODS: A total of 212 women with provoked vestibulodynia (primary = 75 and secondary = 137) participated in the study after completing a gynecologic exam to confirm their diagnosis. MAIN OUTCOME MEASURE: Pelvic floor muscle morphometry was evaluated at rest and during maximal contraction using 3D/4D transperineal ultrasound and pelvic floor muscle function (tone, strength, speed of contraction, endurance) was assessed with a dynamometric speculum. RESULTS: Pelvic floor muscle morphometry at rest and during contraction was not statistically different between women with primary and secondary provoked vestibulodynia (P > .327 adjusted for the duration of symptoms; P > .137 unadjusted t-tests). Regarding pelvic floor muscle function assessed with the dynamometric speculum, no differences were found in tone, strength, speed of contraction, endurance between the 2 groups (P > .144 adjusted for duration of symptoms; P > .118 unadjusted t-tests). CLINICAL IMPLICATIONS: Women with primary and secondary PVD do not differ on pelvic floor muscle morphometric or dynamometric characteristics, suggesting that physical therapy modalities should be offered to both subgroups of PVD. STRENGTHS & LIMITATIONS: The current study used a large and mixed clinical and community sample providing more representative findings. Moreover, the analyses were adjusted for relevant variables such as duration of symptoms. Although the inclusion of nulliparous women below 45 years of age ensured the homogeneity of the sample, it may limit the external validity. CONCLUSION: These findings suggest that primary and secondary subgroups of provoked vestibulodynia cannot be differentiated by morphometric or dynamometric characteristics. Pelvic floor muscles alterations in provoked vestibulodynia are therefore not influenced by the onset of the symptoms. Fontaine F, Dumoulin C, Bergeron S, et al. Pelvic floor muscle morphometry and function in women with primary and secondary provoked vestibulodynia. J Sex Med 2018;15:1149-1157.

Abnormal vaginal microbioma is associated with severity of localized provoked vulvodynia. Role of aerobic vaginitis and Candida in the pathogenesis of vulvodynia.

Localized provoked vulvodynia (LPV) causes introital dyspareunia in up to 14% of premenopausal women. Vaginal infections like candidosis may play a initiating role. The aim of this study was to test a possible association of vaginal microbiota alternations such as Candida vaginitis (CV), aerobic vaginitis (AV) and bacterial vaginosis (BV) with severity of vulvodynia and painful intercourse. In an observational study, Q-tip touch test (score 1 (no pain) to 10 (worst possible pain)) was performed on seven vestibular locations in 231 LPV patients presenting in the Vulvovaginal Disease Clinics in Tienen, Leuven and Antwerp, Belgium. Severity of pain upon attempting sexual intercourse was recorded in a similar scale. Both scales were compared to results from fresh wet mount phase contrast microscopy on vaginal fluid smears tested for abnormal vaginal flora (AVF), BV, AV and CV according the standardized microscopy method (Femicare). Fisher's exact test was used. Average age was 31.3 ± 11.6 years, and 58.8% (n = 132) had secondary vestibulodynia. There was an inverse relation between the presence of Candida in the vaginal smears and pain score (p = 0.03). There was no relation of pain score, nor Q-tip score with BV. LPV patients with Q-tip score above 7 at 5 and/or 7 o'clock or at 1 and/or 11 o'clock had more often AV than women with lower pain scores (30 vs 14.5%, p = 0.01, and 39 vs 14.7%, p < 0.005, respectively). Detailed study of the vaginal microflora in patients demonstrates that the most severe patients suffer more from AV and less from Candida. These abnormalities need to be actively looked for and corrected before considering surgery or other therapies.

Pain, psychological distress and motor pattern in women with provoked vestibulodynia (PVD) - symptom characteristics and therapy suggestions.

BACKGROUND AND AIMS: Provoked vestibulodynia (PVD) represent a longstanding pain syndrome that affects large numbers of women worldwide. However, no standardized guidelines for PVD treatment exist. In a cross-sectional pilot study we examined 30 PVD patients on multidimensional parameters including pain, psychological distress and quality of movement, in order to obtain a broader understanding of the somatic and psychological symptoms in PVD, and for the future to develop better interventions. Additionally, we compare the findings to previously published results regarding the same parameters in women with chronic pelvic pain (CPP). METHODS: Thirty women with PVD recruited from a tertiary care university clinic of gynecology were assessed for demographic data, pain intensity (VAS), psychological distress (GHQ-30 and Tampa scale of Kinesophobia) and quality of movement (standardized Mensendieck test, SMT). RESULTS: Average age of the PVD women was 24.7±3.60 years, 60% of them were in permanent relationships, all were nulliparous, none had been subjected to surgical procedures, 100% were working full or part time and 90% were educated to at least undergraduate level. Mean VAS score was 7.77±1.97 (mean±SD), kinesiophobia 24.4±3.95 and anxiety domain of GHQ-30 9.73±4.06. SMT scores were particularly low for the domains of respiration and gait (less than 50% of optimal scores). CONCLUSIONS: PVD women display reduced quality of movement, especially for gait and respiration patterns, increased level of anxiety and high average pain scores. These findings are similar to what we have previously reported in CPP patients. However, in contrast to CPP group, PVD women are on average younger, have higher work participation, higher education level and have not been subjected to surgical procedures. IMPLICATIONS: Since PVD women display similar, although somewhat less severe, symptom profile than CPP, we suggest that a multidimensional approach to treatment, such as "somatocognitive therapy" should be investigated in this group as it has previously been shown to be promising in treatment of CPP.

An Online Cross-Sectional Comparison of Women With Symptoms of Persistent Genital Arousal, Painful Persistent Genital Arousal, and Chronic Vulvar Pain.

BACKGROUND: Persistent genital arousal disorder (PGAD) is an understudied condition characterized by unwanted physiologic genital arousal in the absence of subjective sexual arousal. Markos and Dinsmore (Int J STD AIDS 2013;24:852-858) theorized that PGAD shares a number of similarities with vulvodynia (unexplained chronic vulvar pain [CVP]), including symptom characteristics and comorbidities. AIM: To compare medical histories, symptom characteristics, pain characteristics, and daily functioning among women with persistent genital pain (PGA) (n = 42), painful PGA (n = 37), and CVP (n = 42) symptoms. METHODS: An online cross-sectional survey was conducted from October 2015 through April 2016. OUTCOMES: Self-report measures of symptoms, diagnosed medical conditions, pain characteristics (McGill Pain Questionnaire), catastrophizing (Pain Catastrophizing Scale), and daily functioning (Functional Status Questionnaire) were collected. RESULTS: All 3 groups reported similar medical diagnoses and high frequencies of other chronic pelvic pain conditions. Women in all 3 groups reported comparable ages at symptom onset and timing of symptom expression (ie, constant vs intermittent). Women in the 2 PGA groups reported significantly greater feelings of helplessness than women in the CVP group. Women in the painful PGA and CVP groups endorsed significantly more sensory terms to describe their symptoms compared with women in the PGA group, whereas women in the painful PGA group reported significantly more affective terms to describe their symptoms compared with women in the CVP group. Women in the 2 PGA groups reported that their symptoms interfered significantly with most areas of daily functioning. CLINICAL IMPLICATIONS: Given the similarities between PGA and CVP symptoms, women with PGA may benefit from similar assessment, treatment, and research approaches. STRENGTHS AND LIMITATIONS: Limitations of the present study include its sole use of self-report measures; the presence of PGA or CVP symptoms was not confirmed by clinical assessment. However, the anonymous design of the online survey could have resulted in a larger and more diverse sample. CONCLUSION: The results of this study provide some initial support for the conceptualization of persistent genital arousal as a subtype of genital paresthesias/discomfort. These results also further highlight the negative impact that PGA symptoms have on many domains of daily living and the need for further research on this distressing condition. Jackowich RA, Pink L, Gordon A, et al. An Online Cross-Sectional Comparison of Women With Symptoms of Persistent Genital Arousal, Painful Persistent Genital Arousal, and Chronic Vulvar Pain. J Sex Med 2018;15:558-567.

Can maximal voluntary pelvic floor muscle contraction reduce vaginal resting pressure and resting EMG activity?

INTRODUCTION AND HYPOTHESIS: The purpose of the present study was to assess whether attempts at a maximal voluntary pelvic floor muscle (PFM) contraction can reduce vaginal resting pressure (VRP) and surface EMG activity in women with and without provoked vestibulodynia (PVD). METHOD: An assessor blinded comparison study included 35 women with and 35 women without PVD. VRP and PFM strength were measured with a high precision pressure transducer connected to a vaginal balloon (Camtech AS, Sandvika Norway). PFM activity was measured before and after three MVCs with surface EMG (NeuroTrac ETS™; Verity Medical, Romsey, UK). Paired sample t test was used to analyze differences within groups and independent sample t test to analyze differences between groups. p value was set at <0.05. RESULTS: Mean age of the participants was 24.3 years (SD 4.7) and mean BMI was 22.0 kg/m2 (SD 2.6). There were no significant differences between the groups in any background variables. PFM contraction led to a statistically significant reduction of VRP in both the PVD (p = 0.001) and the control group (p = 0.027). Surface EMG activity was significantly reduced in the PVD group only (p = 0.001). DISCUSSION: Young, nulliparous women with PVD had significantly lower vaginal resting pressure and sEMG activity after three maximum contractions of the PFM. The results indicate that attempts at voluntary maximal contractions may be investigated as a method of reducing PFM hypertonicity.

Fear-avoidance and Pelvic Floor Muscle Function are Associated With Pain Intensity in Women With Vulvodynia.

OBJECTIVE: To investigate the association between fear-avoidance variables, pelvic floor muscle (PFM) function, pain intensity in women with provoked vestibulodynia (PVD), as well as the moderator effect of partner support. MATERIALS AND METHODS: A sample of 173 women diagnosed with PVD participated in the study. Fear-avoidance variables were assessed with validated self-administered questionnaires: pain catastrophizing (Pain Catastrophizing Scale), pain-related fear (Pain Anxiety Symptoms Scale), and partner support (Partner Support Questionnaire). Pain intensity was evaluated using a numerical rating scale. PFM function, including maximal strength, speed of contraction, flexibility, and muscle tone, was evaluated with a dynamometric speculum. RESULTS: Pain catastrophizing was significantly associated with pain intensity (ß=0.310, P<0.001), partner support (ß=0.194, P=0.004), and PFM flexibility (ß=-0.255, P<0.001). Fear-avoidance, PFM variables, and partner support explained 28.3% of the variance in pain during intercourse (P<0.001). The addition of PFM was of particular interest as it explained a significant addition of 9% of the variance in pain intensity. Partner support was found to moderate the association between pain intensity and catastrophizing. Among women with high partner support, catastrophizing was not significantly related to pain (b=0.150, P=0.142). When partner support was low, catastrophizing was significantly related to pain (b=0.068, P<0.001). DISCUSSION: Findings of this study support that the symptomatology of PVD can be explained partly by fear-avoidance variables and PFM function. This study supports the significant role of PFM function and its importance in the pathophysiology of PVD. It also sheds light on the role of partner support and its moderating effect on pain catastrophizing.