Health and socioeconomic well-being of women with endometriosis and provoked vestibulodynia: Longitudinal insights from Swedish registry data.

Endometriosis and provoked vestibulodynia (PVD) are prevalent pain conditions among women of reproductive age, significantly impacting their quality of life and psychological well-being. However, comprehensive evidence regarding the lifelong health and socioeconomic outcomes for these individuals remains scarce. Additionally, many prior studies rely on limited and sometimes unrepresentative samples. This study aims to inform on the long-term consequences of these disorders by examining health, fertility, and employment outcomes in a cohort of women diagnosed with endometriosis and/or PVD, tracing their experiences from childhood to their 40s. Leveraging nationwide administrative data from Sweden and employing a matched case-control design, we investigate both similarities and differences between women with these diagnoses and those without. Our findings indicate that women diagnosed with endometriosis and/or PVD demonstrate elevated healthcare utilization patterns, commencing in their early teenage years and progressively increasing over time. Notably, disparities in labor market outcomes emerge in their 20s, showcasing lower labor earnings and a rise in sickness benefit receipt. Moreover, our results show a higher likelihood among these women to experience mental health disorders and concurrent chronic pain diseases, as well as infertility. While the association between endometriosis and infertility is well-documented, this study offers novel insights into a potential similar link between PVD and infertility. Our study informs healthcare professionals and policymakers about the considerable burden of compromised health, adverse psychosocial well-being, and reduced productivity in the labor market faced by young women with these common pain conditions. These findings underscore the urgency of addressing the multifaceted challenges encountered by individuals diagnosed with endometriosis and PVD across their lifespan.

Cytokine profiles and their roles in development of provoked vulvodynia.

Provoked, localized, vulvodynia (PVD) is the main subtype of vulvodynia. Although the etiology of PVD is still a topic of debate, inflammation caused by cytokines responding to a dysregulated microbiome is one of the leading proposed theories. Therefore, the purpose of our study is to further explore the cytokine profiles in the study group with PVD using multiplex immunoassays based on electrochemiluminescence. We compared a panel of 26 distinct cytokines levels in the study group with PVD (n = 23) to the control group (n = 18) and cytokine concentrations were measured using MESO QuickPlex SQ 120 instrument with 5 different multiplex assays. Statistical analysis used the Mann-Whitney U test, two-sided p-values, and a significance level of α = 0.05. Differences in cytokine concentrations are described as negligible, small, medium, or large based on Cliff's δ. Concentrations of three cytokines were significantly lower in the PVD group: a large difference in IP-10 (p = 0.029*) and medium differences in IL-1RA4 (p = 0.030*) and IL-12 (p = 0.034*). One cytokine level was significantly higher in the PVD group: a medium difference for IL-6 (p = 0.037*). Due to the lack of consistency in elevation of inflammatory profiles, it is not enough to support persistent inflammation as the etiology behind PVD. However, these findings may indicate there is a possible immune response deficiency in some patients who have PVD. The resemblance of cytokine profile in our study to cytokine profile of people with chronic yeast infection further support this proposed mechanism behind PVD. Future studies involving history and testing for yeast infection are necessary to explore this possibility further.

Effectiveness of Combination of Tibolone and Lactobacilli Plus Lactoferrin in Postmenopausal Women with Vulvar Vestibular Pain: A Preliminary Report.

BACKGROUND: Postmenopausal dyspareunia and vulvar pain are common complaints, affecting about 60% of women within a few years after hormone levels begin to decline (such as estrogen and androgen). Atrophic changes mainly located in the vulvar vestibule and vulnerability to vulvovaginal infections in postmenopause could be predisposing factors to the development of vulvar burning/pain and introital dyspareunia (vestibulodynia secondary to atrophy). Tibolone is the most effective and safe alternative for treating menopausal symptoms. The role of Lactobacilli and lactoferrin shows its effectiveness in the treatment of vaginal microbiota dysbiosis. The aim of the present study was to assess the efficacy of the combination of tibolone and an oral-specific Lactobacilli mixture in combination with bovine lactoferrin as synergistic therapy for the treatment of vestibulodynia related to atrophy. METHODS: In this study, we included 35 postmenopausal women with at least 1 year of amenorrhea, affected by vulvar burning/pain and introital dyspareunia. All participants received treatment with open-label, oral Tibolone 2.5 mg and Lactobacilli mixture (5 × 109 CFU per capsule) in combination with bovine lactoferrin (Respecta®). Each product was taken once daily for 90 days. RESULTS: After 90 d of therapy with TIB+ Respecta®, in 30 women that completed the treatment, there was a statistically significant decrease from the baseline in the mean of the Visual Analog Scale for vulvar burning/pain and a reduction in scores in the pain evaluation test. CONCLUSIONS: This study provides evidence that the combination of TIB+ Respecta® was effective in reducing symptoms related to vestibular pain and hypersensitivity in a postmenopausal setting.

Psychiatric morbidity across the life course and provoked vulvodynia: is it dependent upon the presence of non-stress-related immune dysfunction?

BACKGROUND: Vulvodynia impacts up to 8% of women by age 40, and these women may have a more compromised immune system than women with no vulvar pain history. AIM: Given that psychiatric morbidity is associated with vulvodynia and is known to activate immune inflammatory pathways in the brain and systemically, we sought to determine whether the association between psychiatric morbidity and vulvar pain was independent of or dependent upon the presence of immune-related conditions. METHODS: Women born in Sweden between 1973 and 1996 with localized provoked vulvodynia (N76.3) and/or vaginismus (N94.2 or F52.5) diagnosed between 2001 and 2018 were matched to two women from the same birth year with no vulvar pain. International Statistical Classification of Diseases and Related Health Problems (ICD-9 or -10 codes) were used to identify women with a history of depression, anxiety, attempted suicide, neurotic disorders, stress-related disorders, behavioral syndromes, personality disorders, psychotic disorders, or chemical dependencies, as well as a spectrum of immune-related conditions. The Swedish National Prescribed Drug Register was used to identify women with filled prescriptions of antidepressants or anxiolytics. OUTCOMES: Vulvodynia, vaginismus, or both were outcomes assessed in relation to psychiatric morbidity. RESULTS: Women with vulvodynia, vaginismus, or both, relative to those without vulvar pain, had adjusted odds ratios between 1.4 and 2.3, with CIs highly compatible with harmful effects. When we assessed women with and those without a lifetime history of immune-related conditions separately, we also observed elevated odds ratios in both groups for mood, anxiety, and neurotic and stress disorders. CLINICAL IMPLICATIONS: Documenting psychiatric impairment as a cause or consequence of vulvodynia is critical in clinical practice because psychiatric conditions may impact treatment efficacy. STRENGTHS AND LIMITATIONS: Strengths of this study include a data source that represents the entire population of women in Sweden that is known to be highly accurate because Sweden provides universal healthcare. Limitations include difficulty in making an accurate assessment of temporality between psychiatric morbidity and the first onset of vulvar pain. In addition, because Swedish registry data have limited information on lifestyle, behavioral, and anthropomorphic factors such as smoking, diet, physical activity, and obesity, these conditions could not be assessed as confounders of psychiatric morbidity and vulvar pain. CONCLUSIONS: Immune pathways by which women with psychiatric conditions increase their risk of vulvar pain could be independent from other immune pathways.

6-Methoxyflavone antagonizes chronic constriction injury and diabetes associated neuropathic nociception expression.

Neuropathy is a disturbance of function or a pathological change in nerves causing poor health and quality of life. A proportion of chronic pain patients in the community suffer persistent neuropathic pain symptoms because current drug therapies may be suboptimal so there is a need for new therapeutic modalities. This study investigated the neuroprotective flavonoid, 6-methoxyflavone (6MF), as a potential therapeutic agent and gabapentin as the standard comparator, against neuropathic models. Thus, neuropathic-like states were induced in Sprague-Dawley rats using sciatic nerve chronic constriction injury (CCI) mononeuropathy and systemic administration of streptozotocin (STZ) to induce polyneuropathy. Subsequent behaviors reflecting allodynia, hyperalgesia, and vulvodynia were assessed and any possible motoric side-effects were evaluated including locomotor activity, as well as rotarod discoordination and gait disruption. 6MF (25-75 mg/kg) antagonized neuropathic-like nociceptive behaviors including static- (pressure) and dynamic- (light brushing) hindpaw allodynia plus heat/cold and pressure hyperalgesia in the CCI and STZ models. 6MF also reduced static and dynamic components of vulvodynia in the STZ induced polyneuropathy model. Additionally, 6MF reversed CCI and STZ suppression of locomotor activity and rotarod discoordination, suggesting a beneficial activity on motor side effects, in contrast to gabapentin. Hence, 6MF possesses anti-neuropathic-like activity not only against different nociceptive modalities but also impairment of motoric side effects.

Long-Term Effectiveness of Vestibulectomy for the Treatment of Vulvodynia: A Retrospective Cohort Study.

OBJECTIVE: To evaluate the effectiveness and complication rate of vestibulectomy for vulvodynia. METHODS: A retrospective cohort study in a teaching and university hospital analyzing patients with vulvodynia with insufficient response to conservative treatment who underwent a vestibulectomy. Data from 114 consecutive vestibulectomy procedures done between September 2009 and October 2018 were retrospectively analyzed. All procedures were performed by the same surgeon.The primary outcome was difference in pain scale (6-point Q-tip test, Nociceptive Rating Scale) between preoperative consultation, postoperative visit, and last follow-up consultation. The secondary outcome was surgical complications, such as wound dehiscence and hematoma. RESULTS: Complete data were available for 80 patients. There was a significant reduction in median pain scores of between 65% and 80% on all 6 evaluated vestibular points during Q-tip tests. The median follow-up was 21 months, ranging from 1 to 92 months (interquartile range [IQR]). Overall, 75% of patients needed no further treatment at the end of the follow-up period. In 22.6% (18/80), a limited wound dehiscence was noted. No other complications were reported nor were there any cases of worsening of the complaints. CONCLUSION/DISCUSSION: In this retrospective cohort study, a significant pain reduction occurred after vestibulectomy in patients who were not responding to conservative treatment. The complication rate of this surgical procedure is low. Vestibulectomy seems to be an effective technique for management of vulvodynia.

Mindfulness and Management of Low Desire and Vulvovaginal Pain.

Mindfulness is defined as present-moment, nonjudgmental awareness. By reducing self-criticism, and depression, and increasing self-compassion, attention, and interoceptive awareness, mindfulness has been found across a variety of systematic reviews and meta-analyses to significantly improve sexual desire, sexual pain, and sex-related distress. It helps individuals connect with their bodies, fostering a deeper understanding of sensations and desires while reducing the focus on negative, judgmental, and catastrophic sex-related and pain-related thoughts. By teaching individuals to focus on bare sensations, mindfulness has also been found to significantly reduce vulvovaginal pain intensity with improvements retained a year later.

Psychosocial Factors Associated With Vulvodynia.

OBJECTIVES: We set out to identify the psychosocial factors associated with vulvodynia and the effects on sexuality, mental health, and quality of life. MATERIALS AND METHODS: PubMed, LILACS, Embase, CINAHL, Web of Science, Scopus, and PsycINFO were searched in August 2023. Two authors selected and extracted the data independently. The risk of bias was assessed using the Newcastle-Ottawa Scale for Observational Studies. To rank the strength of evidence, the Grading of Recommendations Assessment, Development and Evaluation Working Group (GRADE) approach was utilized. RESULTS: A total of 3,182 articles were identified. Twenty-two observational studies (8 cohorts and 14 case-controls) met the eligibility criteria and were included, comprising 2,624 patients. Vulvodynia has been associated with psychological factors (anxiety and depression) and social factors (childhood exposure to physical and sexual abuse, posttraumatic stress, and domestic abuse). Concerning sexual function, the most frequent outcomes were dyspareunia and sexual dysfunction. Only one study assessed quality of life, which showed that women with chronic vulvar pain had greater difficulty performing physical activities and experienced negative moods and feelings. The assessment of the risk of bias showed that the average quality of studies was good to excellent. However, the studies failed to select the nonexposed cohort or control group to describe the results, and often, the study population was rather small, which made it impossible to carry out a meta-analysis. CONCLUSIONS: The certainty of evidence for the associations between anxiety and depression, vulvodynia, and sexual functioning suggests that combating these factors could improve overall quality of life in vulvodynia patients.

Spinal neuronal activity and neuroinflammatory component in a mouse model of CFA-induced vestibulodynia.

Vestibulodynia is a complex pain disorder characterized by chronic discomfort in the vulvar region, often accompanied by tactile allodynia and spontaneous pain. In patients a depressive behaviour is also observed. In this study, we have used a model of vestibulodynia induced by complete Freund's adjuvant (CFA) focusing our investigation on the spinal cord neurons and microglia. We investigated tactile allodynia, spontaneous pain, and depressive-like behavior as key behavioral markers of vestibulodynia. In addition, we conducted in vivo electrophysiological recordings to provide, for the first time to our knowledge, the characterization of the spinal sacral neuronal activity in the L6-S1 dorsal horn of the spinal cord. Furthermore, we examined microglia activation in the L6-S1 dorsal horn using immunofluorescence, unveiling hypertrophic phenotypes indicative of neuroinflammation in the spinal cord. This represents a novel insight into the role of microglia in vestibulodynia pathology. To address the therapeutic aspect, we employed pharmacological interventions using GABApentin, amitriptyline, and PeaPol. Remarkably, all three drugs, also used in clinic, showed efficacy in alleviating tactile allodynia and depressive-like behavior. Concurrently, we also observed a normalization of the altered neuronal firing and a reduction of microglia hypertrophic phenotypes. In conclusion, our study provides a comprehensive understanding of the CFA-induced model of vestibulodynia, encompassing behavioral, neurophysiological and neuroinflammatory aspects. These data pave the way to investigate spinal cord first pain plasticity in vestibulodynia.

Beyond vulvodynia: from a correct diagnosis to a multidisciplinary care program. A referral center experience.

BACKGROUND: Vulvodynia is a chronic pain condition without an identifiable cause. As such, it is a diagnosis of exclusion, and all other causes of vulvar pain should be excluded. Although a standard treatment for vulvodynia has not been established yet, multidisciplinary care programs appear to be effective. PUROPOSE: The aim of this retrospective monocentric study was to analyze the prevalence of vulvodynia among women referred to our institution for a suspected diagnosis and to evaluate the efficacy of a multidimensional treatment plan. The primary outcome was the prevalence of vulvodynia following differential diagnosis. Secondary outcomes included: prevalence of the differential diagnoses, symptom resolution rate following treatment, and the relation between persistence of symptoms and (a) patients' age; (b) coexisting chronic overlapping pain conditions (COPCs). RESULTS: After having ruled out all other causes of vulvar pain, only 40.1% of women were considered as affected by vulvodynia. The most frequent differential diagnoses included lower genital tract infections (25.3%), vulvar lichen sclerosus (17.6%) and vulvovaginal atrophy (8.2%). Following a multidisciplinary care program, resolution of symptoms was observed in 13.6% cases, improvement in 64.3% and persistence in 21.9%. We did not find a statistically significant association between persistence of symptoms and age > 38 years (OR 2.10; p = 0.30). Women with one or more COPCs other than vulvodynia had a 75% increased risk of not obtaining a resolution of symptoms (OR 1.75; p = 0.44). CONCLUSION: A thorough differential diagnosis and a multidisciplinary care program may represent a first way out of the muddle in the management of these patients.

Vestibulodynia: Clinical characteristics, first-line treatments, and factors associated with escalation of treatment with EMG-guided injections of botulinum toxin in a retrospective french cohort study.

BACKGROUND: Vestibulodynia is a highly prevalent chronic pain disorder affecting the vulva having a major impact on women's physical, psychological, and sexual well-being. It remains an underrecognized disease that responds insufficiently to therapies such as physiotherapy and medication. AIM: To assess the global efficacy of first-line therapies and factors associated with treatment escalation in women with vestibulodynia. PATIENTS AND METHODS: This retrospective cohort study was conducted at the dermatology outpatient clinic of the University Hospital in Besancon (France) between 2013 and 2017 and follow-up until 2021. RESULTS: Among 132 patients, the mean [standard deviation] age at diagnosis was 27.2 [±9.45] years, with an average duration of symptoms of 42.3 [±37.92] months. Most cases comprised provoked (75.0%) or secondary (72.7%) vestibulodynia. At least one comorbid pain or psychologic condition was identified respectively in 63 (47.7%) and 23 patients (54.5%). Vulvar hyperesthesia associated with pelvic floor muscle dysfunction was present in 121 patients (91.6%) and vulvar erethism was noted in 94 patients (71.2%). First-line treatments consisted of pelvic floor physiotherapy with biofeedback in 85% of patients, associated with amitriptyline in 36% of cases, and of additional lidocaine cream in 17%. Fifty-two patients (39%) presented at least a good response to first-line treatment, with only 21 (15%) being in complete remission, irrespective of therapeutic strategy (p = 0.25). Botulinum toxin injections were performed in 54 patients. Patients with either primary vestibulodynia (p = 0.04) or spontaneous vestibulodynia (p = 0.03) were more likely to receive this treatment. CONCLUSION: Our study highlights the current lack of efficacy of first-line treatments in vestibulodynia. Considering the high prevalence of muscular dysfunction, botulinum toxin injections are of particular interest despite a lack of randomized controlled trials in this indication.

Efficacy of Rehabilitative Techniques on Pain Relief in Patients With Vulvodynia: A Systematic Review and Meta-Analysis.

OBJECTIVE: Vulvodynia is a chronic clinical condition characterized by provoked or non-provoked vulvar pain for at least 3 months of unknown etiology. The onset of vulvodynia involves a complex interplay of peripheral and central pain mechanisms, such as pelvic floor muscle and autonomic dysfunction, and interpersonal factors. A stepwise approach of pelvic floor physical therapy as medical management is suggested. In this scenario, by this meta-analysis of randomized controlled trials, we aimed to evaluate the efficacy of rehabilitation interventions in patients with vulvodynia. METHODS: On October 13, 2022, PubMed, Scopus, and Web of Science were systematically searched for randomized controlled trials that assessed the efficacy of the rehabilitative approach to pain during intercourse in patients with vulvodynia. The quality assessment was performed with the Cochrane risk-of-bias tool for randomized trials. The trial registration number is CRD42021257449. At the end of the search, 9 studies were included for a total of 332 patients. A pairwise meta-analysis was performed to highlight the efficacy of rehabilitative approaches for reducing pain during intercourse, as measured with a visual analog scale or a numerical rating scale. RESULTS: Meta-analysis showed that all these rehabilitative approaches had an overall effect size of -1.43 (95% CI = -2.69 to -0.17) in decreasing vulvodynia pain in terms of the visual analog scale. In the subgroup analysis, a significant effect size in acupuncture (effect size = -2.36; 95% CI = -3.83 to -0.89) and extracorporeal shockwave therapy (effect size = -2.94; 95% CI = -4.31 to -1.57; I2 = 58%) was observed. According to the Cochrane risk-of-bias tool, a low risk of bias for outcome selection in 89% of studies. CONCLUSION: Findings from this meta-analysis suggested that the physical agent modalities and complementary medicine techniques in people with vulvodynia appear to be more effective than placebo, sham, or waiting list. Further evidence on physical agent modalities and complementary therapies are warranted in the future. IMPACT: This was the first systematic review and meta-analysis of randomized controlled trials to provide evidence on the efficacy of rehabilitation interventions in patients with vulvodynia.

Exploring Localized Provoked Vulvodynia: Insights from Animal Model Research.

Provoked vulvodynia represents a challenging chronic pain condition, characterized by its multifactorial origins. The inherent complexities of human-based studies have necessitated the use of animal models to enrich our understanding of vulvodynia's pathophysiology. This review aims to provide an exhaustive examination of the various animal models employed in this research domain. A comprehensive search was conducted on PubMed, utilizing keywords such as "vulvodynia", "chronic vulvar pain", "vulvodynia induction", and "animal models of vulvodynia" to identify pertinent studies. The search yielded three primary animal models for vulvodynia: inflammation-induced, allergy-induced, and hormone-induced. Additionally, six agents capable of triggering the condition through diverse pathways were identified, including factors contributing to hyperinnervation, mast cell proliferation, involvement of other immune cells, inflammatory cytokines, and neurotransmitters. This review systematically outlines the various animal models developed to study the pathogenesis of provoked vulvodynia. Understanding these models is crucial for the exploration of preventative measures, the development of novel treatments, and the overall advancement of research within the field.

Help-seeking experiences and intimate partner support in vulvodynia: A qualitative exploration.

BACKGROUND: Vulvodynia is a poorly understood chronic pain condition characterized by persistent and unexplained pain in the vulva. Given the intimate nature of the pain, partners may play an important role in promoting self-management and help-seeking behaviours among women with vulvodynia. OBJECTIVES: The current study aimed to explore the role of partner support in pain experiences and help-seeking behaviours among women with vulvodynia. DESIGN: A qualitative interpretive design was used. METHODS: Ten women with vulvodynia (M age = 37.9 years) were interviewed using a semi-structured non-directive topic guide. Data were analysed using reflexive thematic analysis. RESULTS: Three themes around help-seeking experiences were constructed from the data: (1) 'It's Been a Battle' - Failed by the Healthcare System; (2) 'It's Just the Vulva' - Dismissed by Healthcare Professionals; and (3) 'I Diagnosed Myself' - The Patient Becomes the Expert. Participants described negative help-seeking experiences characterized by long delays to diagnosis, lack of awareness and understanding from healthcare professionals, minimization of symptoms, and having to advocate for and demand care. A further three themes pertaining to partner support were also developed: (1) 'That Person to Listen to You' - Source of Emotional Support; (2) 'Why Don't You Try This?' - Finding Solutions Together; and (3) 'He Forgets that it's Still There' - Vulvodynia is a Foreign Concept. Partners provided emotional support and showed empathy and understanding, and practical support by accompanying women to medical appointments and help with pain management. However, participants felt partners' understanding of vulvodynia was limited and that this impacted their relationships. CONCLUSIONS: Findings highlight a lack of continuity of care and multidisciplinary approach to treatment, with help-seeking experiences being mainly negative in this sample. Increasing public awareness of vulvodynia and improving healthcare access is crucial to improving physical and psychological outcomes for this group. Partners can play an important role in supporting people with vulvodynia; however, other outlets of support should be further explored.

Understanding How Women with Vulvodynia Seek Help and Get Support from Their PartnersVulvodynia is a condition where women experience persistent and unexplained pain in the vulva. This pain can be quite personal and difficult to deal with. In this study, we wanted to understand how partners of women with vulvodynia help them cope with the pain and seek medical help. We interviewed 10 women with vulvodynia about their experiences of accessing healthcare for their symptoms, and how their partners affected these experiences. Many women faced challenges when seeking medical help, like delays in getting a diagnosis, healthcare professionals not understanding their condition, and their symptoms being downplayed. Women often had to be their own experts and advocate for their care. Partners of these women provided emotional and practical support, like going with them to medical appointments and helping them to manage the pain. However, some women felt their partners did not fully understand vulvodynia, and their worries sometimes strained their relationships. In conclusion, the study showed that there is a need for better healthcare for women with vulvodynia, including more awareness and easier access to treatment. Partners can be supportive, but other forms of support, for example, from friends, family, and other people with experience of vulva pain, should also be explored.

Development of a core outcome set for treatment studies for provoked vestibulodynia.

BACKGROUND: There is an inconsistency in treatment outcomes used in clinical trials for provoked vestibulodynia (PVD), which makes it impossible to compare the effects of different interventions. AIM: In this study, we completed the first step in creating a core outcome set (COS), defining what outcomes should be measured in clinical trials for PVD. METHODS: Identification of outcomes used in studies was done by extracting data from clinical trials in a recently published systematic review and via review of clinical trials for PVD registered on ClinicalTrials.gov. The COS process consisted of 2 rounds of Delphi surveys and a consensus meeting, during which the final COS was decided through a modified nominal group technique. OUTCOMES: Consensus on what outcomes to include in a COS for PVD. RESULTS: Forty scientific articles and 92 study protocols were reviewed for outcomes. Of those, 36 articles and 25 protocols were eligible, resulting in 402 outcomes, which were then categorized into 63 unique outcomes. Participants consisted of patients, relatives/partners of patients, health care professionals, and researchers. Out of 463 who registered for participation, 319 and 213 responded to the first and second surveys, respectively. The consensus meeting consisted of 18 members and resulted in 6 outcomes for the COS to be measured in all treatment trials regardless of intervention: insertional pain (nonsexual), insertional pain (sexual), provoked vulvar pain by pressure/contact, pain-related interference on one's life, pain interference on sexual life, and sexual function. CLINICAL IMPLICATIONS: Critical outcomes to be measured in clinical trials will allow for accurate comparison of outcomes across treatment interventions and provide solid treatment recommendations. STRENGTHS AND LIMITATIONS: The major strengths of the study are the adherence to methodological recommendations and the intentional focus on aspects of diversity of participating stakeholders (eg, status such as patients with lived experience and researchers, inclusiveness with respect to sexual identity), the latter of which will allow for broader application and relevance of the COS. Among the limitations of the study are the low rate of participants outside North America and Europe and the lower response rate (about 50%) for the second Delphi survey. CONCLUSION: In this international project, patients, health care professionals, and researchers have decided what critical outcomes are to be used in future clinical trials for PVD. Before the COS can be fully implemented, there is also a need to decide on how and preferably when the outcomes should be measured.

Guided internet-based acceptance and commitment therapy for provoked vestibulodynia: A randomized controlled trial.

BACKGROUND: Provoked vestibulodynia (PVD) causes suffering in many women's lives due to its impact on relationships, sexual functioning and functioning in other key domains. OBJECTIVE: Here, we report a randomized controlled trial conducted to examine whether Acceptance and Commitment Therapy (ACT) with a focus on values-based exposure, delivered online, benefits women with PVD. METHODS: Participants (n = 88) were randomized to either guided online ACT for 10 weeks or a wait-list control group. Outcomes were assessed at baseline, post treatment and 1 year later. Analyses were based on intention to treat using linear mixed models. RESULTS: There were significant group differences on the primary outcomes, Female Sexual Index and Female Sexual Distress Scale, in favour of online ACT with moderate effect sizes. Differences were also found on several secondary outcomes and therapeutic process measures, all in favour of ACT. No differences were found at post-treatment for depression or anxiety. At the 1-year follow-up, results were maintained and a difference between baseline and follow-up was also found for depression. CONCLUSION/SIGNIFICANCE: In summary, a relatively brief, guided, online version of ACT appears to produce benefits for women with PVD and related impacts on daily functioning. 50% to 60% of the women who participated in the treatment reliably improved in sexual functioning and distress.

Psychosexological correlates of 372 women with vulvodynia, overactive pelvic floor, postcoital cystitis, and interstitial cystitis.

BACKGROUND: Among the plethora of urogynecological conditions possibly affecting women, some of them, less explored, have significant impacts on sexological and psychological health, with a mutual influence. AIM: The aim of this study was to investigate the sexological and psychological correlates of four urogynecological pathologies in a sample of women of childbearing age: overactive pelvic floor, vulvodynia, postcoital cystitis, and interstitial cystitis. Women cured of these conditions were also included, to assess the same aspects after the remission of physical symptoms. METHODS: We recruited 372 women with an average age of 33.5 years through an online platform shared by a popular forum for women with urogynecological pathologies between March and May 2021. The participants filled out a socio-anamnestic questionnaire and a set of psychometric tests. OUTCOMES: Participant data were collected by use of the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Toronto Alexithymia Scale-20, Female Sexual Function Index, and Orgasmometer-F, and the SPSS (Statistical Package for Social Sciences) v.26 was used for data analysis. RESULTS: Overactive pelvic floor was reported by 66.4% of the women, vulvodynia by 55%, postcoital cystitis by 58.8%, and interstitial cystitis by 8.3%, and these conditions were often comorbid with each other, with 9.4% and 7% of women reporting having suffered psychological and sexual abuse, respectively. The presence of past abuse was correlated with overactive pelvic floor (P < .05), vulvodynia (P < .01), and major depression (P < .01). Significantly more depression occurred in women with vulvodynia than in the other subgroups (P < .05), except for women with only an overactive pelvic floor. There was no difference between the subgroups in the occurrence of alexithymia, sexual function, and orgasm (P < .05). Interestingly, the prevalence of sexual dysfunction increased in cured women. CLINICAL IMPLICATIONS: The lack of significant differences, except for depression, between the pathological subgroups suggests a similar clinical and psychological relevance of the four pathologies studied. The persistence of sexual dysfunctions in cured women may be related to a residual dysfunctional relational modality with the partner. STRENGTHS AND LIMITATIONS: The evaluation of both psychological and sexological variables in a group of less-explored urogynecological conditions represents a strength of this study, while a lack of a face-to-face assessment could represent a limitation. CONCLUSION: The results of the present study should promote psychosexological interventions in women with these diseases, both during the pathological state and after remission.

Efficacy of in-office lysis of clitoral adhesions with excision of keratin pearls on clitoral pain and sexual function: a pre-post interventional study.

BACKGROUND: Keratin pearls are foci of central keratinization within concentric layers of squamous cells that can form under the clitoral prepuce and cause pain (clitorodynia); in-office removal of keratin pearls may reduce clitoral pain and improve sexual function. AIM: This study aims to investigate clitoral pain and sexual function in women with partial clitoral phimosis and keratin pearls before and after in-office lysis of clitoral adhesions with keratin pearl excision (LCA-KPE). METHODS: A pre-post interventional study evaluated patients who underwent LCA-KPE between January 2017 and February 2023 in 2 metropolitan gynecology clinics specializing in vulvar pain. Patients presenting with keratin pearls and partial clitoral phimosis identified through retrospective chart review were asked to complete postprocedure questionnaires and provide subjective responses on clitoral discomfort, sexual function, sexual distress, and their experience with in-office LCA-KPE. Bivariate analyses with paired t tests were conducted to determine the effect of LCA-KPE. Qualitative data were analyzed with thematic coding. OUTCOMES: An 11-point pain visual analog scale was utilized to determine pre- and postprocedure clitoral discomfort and difficulty with orgasm. Female sexual dysfunction was measured with the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised. RESULTS: A total of 32 of 74 patients who met inclusion criteria completed postprocedure surveys (43% response rate). Mean clitoral pain for respondents was 6.91 at baseline and 2.50 after LCA-KPE (P < .001). Mean difficulty with orgasm was significantly decreased from 5.45 at baseline to 3.13 after LCA-KPE (P < .001). Participants had a mean FSFI total score of 17.68 after treatment compared with a mean total baseline FSFI of 12.12 (P = .017). The mean FSFI score for pain was 2.43 at follow-up compared with 1.37 at baseline (P = .049). There was no significant difference in the mean Female Sexual Distress Scale-Revised score before vs after the procedure (P = .27). Qualitative themes described the procedure as painful but worthwhile, with 77% of participants reporting the overall experience as positive. Recurrence rate overall was 28%, with a median of 2 repeat procedures. CLINICAL IMPLICATIONS: Recognizing keratin pearls as a structural cause of clitoral pain and offering in-office treatment is an important tool in addressing clitorodynia and improving sexual function. STRENGTHS AND LIMITATIONS: This is the largest study to date documenting the occurrence, identifying associated pain conditions, and evaluating procedural outcomes for clitoral keratin pearls. This study was limited by a relatively small sample size. CONCLUSION: In-office LCA-KPE significantly reduced clitoral discomfort and difficulty with orgasm.

Immunohistochemical staining with CD117 and PGP9.5 of excised vestibular tissue from patients with neuroproliferative vestibulodynia.

BACKGROUND: Neuroproliferative vestibulodynia (NPV), a provoked genital pain characterized by severe allodynia and hyperalgesia, is confirmed in excised vestibular tissue by immunohistochemical staining (>8 CD117-positive immunostained cells/100× microscopic field) rather than by hematoxylin and eosin staining. AIM: In this study we sought to assess immunostaining of tissue samples obtained during vestibulectomy surgery and to correlate results with patient outcomes. METHODS: Patients (n = 65) meeting criteria for NPV who underwent vestibulectomy during the period from June 2019 through December 2022 formed the study cohort. We performed assessment of pathology of vestibular tissues by use of immunohistochemical staining, including quantitation of mast cells by CD117 (mast cell marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments. OUTCOMES: Outcomes included density of CD117 and PGP9.5 immunostaining in the 1:00-11:00 o'clock and 12:00 o'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement. RESULTS: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments. OUTCOMES: Outcomes included density of CD117 and PGP9.5 immunostaining in the 1:00-11:00 o'clock and 12:00 o'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement. RESULTS: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the median area of CD117 immunostaining was similar in both regions (0.69% and 0.73%). The median area of PGP9.5 immunostaining was 0.47% and 0.31% in these same regions. Pain scores determined with cotton-tipped swab testing were nominally higher in lifelong vs acquired NPV patients, reaching statistical significance in the 1:00-11:00 o'clock region (P < .001). The median score for the McGill Pain Questionnaire affective subscale dimension was also significantly higher in lifelong vs acquired NPV patients (P = .011). No correlations were observed between hematoxylin and eosin results and density of mast cells or neuronal markers. Of note, 63% of the patient cohort reported having additional conditions associated with aberrant mast cell activity. CLINICAL IMPLICATIONS: The pathology of NPV is primarily localized to the vestibular epithelial basement membrane and subepithelial stroma with no visible vulvoscopic findings, making clinical diagnosis challenging. STRENGTHS AND LIMITATIONS: Strengths of this study include the large number of tissues examined with what is to our knowledge the first-ever assessment of the 12:00 vestibule. Major limitations are specimens from a single timepoint within the disease state and lack of control tissues. CONCLUSIONS: Performing immunohistochemical staining of excised vestibular tissue with CD117 and PGP9.5 led to histometric confirmation of NPV, indications that NPV is a field disease involving all vestibular regions, validation for patients whose pain had been ignored and who had experienced negative psychosocial impact, and appreciation that such staining can advance knowledge.

Relationship Between Childhood Sexual Abuse, Obesity, and Vulvodynia in Adulthood.

OBJECTIVE: The aim of the study is to assess the relationship between childhood sexual abuse, obesity, and vulvodynia among adult women participating in a population-based longitudinal vulvodynia study. MATERIALS AND METHODS: Surveys assessed health status, diagnoses, risk factors, and screening test outcomes for women with vulvodynia. Associations between childhood sexual abuse (CSA) and obesity, CSA and vulvodynia, and obesity and vulvodynia were investigated. A multivariate model was used to determine if obesity mediates and/or modifies the relationship between CSA and vulvodynia. RESULTS: Of 2,277 women participating in the study, 1,647 completed survey data on CSA at 18 months, body mass index at 24 months, and vulvodynia over the first 54 months of the survey. Mean age was 50.9 ± 15.8 years. Overall, race and ethnicity were 77.4% White, 15.7% Black, 2.4% Hispanic, and 4.5% other. Five hundred thirty-nine participants (32.7%) were obese (body mass index >30) and 468 (28.4%) were overweight. Physical CSA before age of 18 years was reported by 20.0% ( n = 329). During the study, 22.0% ( n = 362) screened positive for vulvodynia on one or more surveys. After controlling for demographic variables, both obesity and screening positive for vulvodynia were associated with a history of CSA before age of 18 years ( p = .013 and p < .001, respectively), but obesity was not associated with screening positive for vulvodynia ( p = .865). In addition, multivariate analysis indicated no mediation of the CSA/vulvodynia relationship by obesity. CONCLUSIONS: Although obesity and vulvodynia were independently associated with a history of CSA, obesity did not mediate or modify the relationship between CSA and vulvodynia in adulthood.