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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.

ABSTRACT: 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.

SUBMITTER: Labus JS

PROVIDER: S-EPMC8438271 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Vulvodynia is a chronic vulvar pain disorder and fibromyalgia is a chronic widespread musculoskeletal pain disorder, both of unknown etiology. Association of these conditions is well documented. Intravaginal algometer measurement of tenderness to pressure applied to the pelvic floor muscles helps define vulvodynia associated with musculoskeletal factors. Women with both vulvodynia and fibromyalgia might have increased pelvic muscle pain compared to women with vulvodynia alone, defining the possible link of these 2 conditions.We sought to: (1) correlate pain intensity during the nongenital tender point tenderness examination to pain intensity with the vaginal algometer in women with provoked vestibulodynia, and (2) determine whether subjects with provoked vestibulodynia and fibromyalgia had higher pain intensity scores with the vaginal algometer than those without fibromyalgia.In all, 92 subjects referred for vulvar pain were confirmed to have provoked vestibulodynia using the cotton swab test. A diagnosis of fibromyalgia was made if pain was present (numeric rating scale >1) in at least 11 sites of the 18-point nongenital tender point tenderness exam. Vaginal pain sensitivity was measured using an intravaginal pressure algometer, where 0.1, 0.3, and 0.5 kg/cm2 forces were applied digitally in random assignment by force and location to the right and left iliococcygeus muscle regions and the posterior vaginal wall. Both tender point tenderness and algometer pain intensity were reported on a 0 (no pain) to 10 (worse pain) numeric rating scale. Correlations were computed between the composite pain intensity (total of rating scale from each pressure threshold at specified site) of nongenital and those of iliococcygeus regions and the posterior vaginal wall. Independent t tests were used to determine differences in iliococcygeus regions and the posterior vaginal algometer pain ratings and presence or absence of fibromyalgia. The significance level was at P < .05. The data were expressed as mean ± SD.A significant correlation was found between numeric rating scale pain scores on the nongenital tender point tenderness exam and algometer testing on the iliococcygeus region (r = 0.44, P < .0001) and the posterior vaginal wall (r = 0.45, P < .0001). Subjects with fibromyalgia by tender point tenderness had significantly higher iliococcygeal pain (6.14 ± 2.07 vs 3.74 ± 2.22, P = .0001) and posterior vaginal wall pain (5.67 ± 2.10 vs 3.07 ± 2.16, P < .0001) than women without fibromyalgia by tender point tenderness.Women with provoked vestibulodynia who experience more severe pain with nongenital tender point palpation also experience more deep vaginal pain on pelvic exam. Those who fulfill the diagnosis of fibromyalgia show significantly more intense deep vaginal pain to palpation of iliococcygeus muscles and posterior vaginal wall. Further research using a more precise definition of fibromyalgia is necessary to confirm this relationship, but findings suggest that women with provoked vestibulodynia coexisting with fibromyalgia have greater risk of superimposed vaginal muscle pain and may be candidates for early adjunctive pelvic floor physical therapy. These findings need to be explored in women with generalized, nonprovoked vulvodynia.

Project description:IntroductionPelvic pain and vulvar pain are common conditions in women. In this study, we sought to characterize the clinical picture of patients with concurrent pelvic pain and provoked vestibulodynia (PVD).AimTo analyze the association between sexual/clinical characteristics and a diagnosis of PVD among women with pelvic pain.MethodsCross-sectional analysis of a prospective registry at a tertiary referral center for pelvic pain and endometriosis, involving consecutive non-menopausal sexually active patients 18-49 years-old seen by a single gynecologist from January 2016-December 2017. The sample was divided into 2 groups: pelvic pain with PVD; and pelvic pain alone (without PVD).Main outcome measuresSuperficial dyspareunia and deep dyspareunia on a 11-point numeric rating scale, and the sexual quality-of-life subscale of the Endometriosis Health Profile-30 (0-100%).ResultsThere were 129 patients that met study criteria: one third with pelvic pain and PVD (n = 42) and two-thirds with pelvic pain alone (without PVD) (n = 87). Women with pelvic pain and PVD had significantly more severe superficial dyspareunia ≥7/10 (OR = 12.00 (4.48-32.16), P < .001), more severe deep dyspareunia ≥7/10 (OR = 4.08 (1.83-9.10), P = .001), and poorer sexual quality of life (Endometriosis Health Profile-30 ≥50%) (OR = 4.39 (1.67-11.57), P = .002), compared with the group with pelvic pain alone. Women with pelvic pain and PVD also had more anxiety, depression, and catastrophizing, more frequent tenderness of the bladder and pelvic floor, and more common diagnosis of painful bladder syndrome. On the other hand, there were no significant differences between the 2 groups in terms of dysmenorrhea, chronic pelvic pain, abdominal wall allodynia, positive Carnett test for abdominal wall pain, functional quality of life, endometriosis, and irritable bowel syndrome.ConclusionsIn the pelvic pain population, PVD may be associated with more negative impact on dyspareunia, sexual quality of life, and bladder/pelvic floor function, but it may not significantly impact abdominopelvic pain or day-to-day function in general. Bao C, Noga H, Allaire C, et al. Provoked Vestibulodynia in Women with Pelvic Pain. Sex Med 2019;7:227-234.

Project description:BackgroundProvoked vestibulodynia (PVD) is a prevalent chronic pain condition especially among young women. Pain is localized to the vulvar vestibule and is provoked by touch or pressure, such as penetrative intercourse. PVD can have profound consequences, adversely affecting a woman's sexual life, relation to her partner, and her psychological health. There is an urgent need for well-designed randomized clinical trials (RCTs) to identify the most effective interventions for this neglected women's health condition.AimsThe primary aim of this study is to assess the feasibility of undertaking a full-scale RCT of somatocognitive therapy (SCT), a multimodal physiotherapy intervention, for women with PVD. The secondary aim is to evaluate the implementation and acceptability of SCT and its potential treatment effectiveness in PVD. In the full-scale RCT, SCT will be compared to standard PVD treatment.MethodsA multimethod feasibility study with a single-arm before-after trial and qualitative interviews. Ten women with PVD, aged 18-33 were recruited from the Vulva Clinic at Oslo University Hospital. The intervention took place at Oslo Metropolitan University. Participants were assessed at baseline, post-treatment, and the 8-month follow-up with the tampon test and self-report questionnaires. The main feasibility outcomes were evaluation of recruitment rate, adherence to assessment tools, and follow-up rate. The participants' experiences with the primary outcome and the intervention were explored with semi-structured interviews.ResultsTen out of 18 eligible patients were recruited over 11 weeks. None were lost to follow-up. Adherence to self-report questionnaires was excellent. Adherence to tampon tests and to the reporting of treatments was good, whereas adherence to the 14-day diary was poor. No adverse events were reported. The tampon test was suboptimal as a primary outcome. SCT was found to be an acceptable treatment, based on Global Perceived Effect scores and the participants' experiences.ConclusionThe findings suggest that it is feasible to deliver a full-scale RCT of the SCT intervention for women with PVD. Some changes are suggested to optimize the protocol, such as increasing recruitment sites, change of primary outcome measures, and adding a booster session.Trial registrationClinicalTrials.gov NCT04208204 . Retrospectively registered on December 23, 2019.

Project description:Knowledge of female genital anatomy and physiology is often inadequate or incorrect among women. Precise patient-physician conversations can be inhibited by a reluctance or inability to speak accurately about the vulva and vagina, with the terms often being used interchangeably. There is a paucity of scientific evidence and clinical guidelines to support women and physicians in ensuring best practices in feminine hygiene. In this review, the unmet needs in the field are highlighted. Evidence is provided for the complex array of physiological and pathological systems, mechanisms and behaviours that either protect or, if inappropriate, predispose the vulva and vagina to infections, irritation or other conditions. The need for attention to perineal health is recommended, given the interdependence of perineal and vulvar microbiota and the risk of colonic pathogens reaching the vulva and the vagina. Differences in feminine hygiene practices can vary widely across the world and among varying age groups, and suboptimal habits (such as vaginal douching or the use of certain cleansers) can be associated with increased risks of vulvar and vaginal conditions. Critical areas for discussion when advising women on their intimate health include: advice surrounding aesthetic vulvar cosmetic trends (such as depilation and genital cosmetic surgery), bowel health and habits, and protection against sexually transmitted infections. Routine, once-daily (maximum twice-daily) washing of the vulva with a pH-balanced, mild cleanser is optimal, ideally soon after bowel voiding, when feasible. Due to the finely balanced ecosystems of the vulva, the vagina and the perineal area, a scientific and clinical perspective is essential when determining the most appropriate vulvar cleansers based on their components. Correct intimate care may contribute to improved genital and sexual health and overall well-being. An increased awareness of correct practices will empower women to be the advocates of their own intimate health.

Project description:BACKGROUND:Provoked vestibulodynia is the most common form of vulvodynia. Despite its high prevalence and deleterious sexual, conjugal, and psychological repercussions, effective evidence-based interventions for provoked vestibulodynia remain limited. For a high proportion of women, significant pain persists despite the currently available treatments. Growing evidence suggests that the central nervous system (CNS) could play a key role in provoked vestibulodynia; thus, treatment targeting the CNS, rather than localized dysfunctions, may be beneficial for women suffering from provoked vestibulodynia. In this study, we aim to build on the promising results of a previous case report and evaluate whether transcranial direct-current stimulation, a non-invasive brain stimulation technique targeting the CNS, could be an effective treatment option for women with provoked vestibulodynia. METHODS/DESIGN:This single-center, triple-blind, parallel group, randomized, controlled trial aims to compare the efficacy of transcranial direct-current stimulation with sham transcranial direct-current stimulation in women with provoked vestibulodynia. Forty women diagnosed with provoked vestibulodynia by a gynecologist, following a standardized treatment protocol, are randomized to either active transcranial direct-current stimulation treatment for ten sessions of 20 minutes at an intensity of 2 mA or sham transcranial direct-current stimulation over a 2-week period. Outcome measures are collected at baseline, 2 weeks after treatment and at 3-month follow-up. The primary outcome is pain during intercourse, assessed with a numerical rating scale. Secondary measurements focus on the sexual function, vestibular pain sensitivity, psychological distress, treatment satisfaction, and the patient's global impression of change. DISCUSSION:To our knowledge, this study is the first randomized controlled trial to examine the efficacy of transcranial direct-current stimulation in women with provoked vestibulodynia. Findings from this trial are expected to provide significant information about a promising intervention targeting the centralization of pain in women with provoked vestibulodynia. TRIAL REGISTRATION:Clinicaltrials.gov, NCT02543593 . Registered on September 4, 2015.

Project description:Purulent vulvar discharges, primarily caused by genito-urinary tract infections, are an important source of economic loss for swine producers due to sow culling and mortality. However, the agents that compose the vaginal microbiota of sows and their changes during infections are not well understood. The first goal of this study was to characterize and compare the vaginal bacterial content of healthy (HE, n = 40) and purulent vulvar discharge sows (VD, n = 270) by a culture-dependent method and MALDI-TOF MS identification. Secondly, we performed 16S rRNA targeted metagenomic approach (n = 72) to compare the vaginal microbiota between these groups. We found a wide variety of bacteria, with Proteobacteria, Firmicutes, and Bacteroidota being the most abundant phyla in both groups, as well as Escherichia-Shigella, Streptococcus, and Bacteroides at the genus level. Most agents identified in the sequencing method also grew in the culture-dependent method, showing the viability of these bacteria. Alpha diversity did not differ between HE and VD sows, regarding sample richness and diversity, but a beta-diversity index showed a different microbiota composition between these groups in two tested herds. ANCOM analysis revealed that Bacteroides pyogenes were more abundant in VD females and can be a marker for this group. Other agents also require attention, such as the Streptococcus dysgalactiae and Staphylococcus hyicus found in remarkably greater relative abundance in VD sows. Network analysis revealed important positive correlations between some potentially pathogenic genera, such as between Escherichia-Shigella, Trueperella, Streptococcus, Corynebacterium, and Prevotella, which did not occur in healthy sows. We conclude that the alteration of the vaginal microbiota between healthy and purulent vulvar discharge sows, although not extreme, could be due to the increase in the relative abundance of specific agents and to associations between potentially pathogenic bacteria.

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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.

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