Is Vulvodynia Associated With an Altered Vaginal Microbiota?: A Systematic Review.

INTRODUCTION: Vulvodynia is defined as vulvar pain of at least 3 months' duration, without clear identifiable cause, which may have potential associated factors. It can have a significant impact on women's quality of life due to a combination of physical pain, emotional distress, and limited treatment options. Despite affecting a considerable number of women worldwide, the causes and underlying mechanisms of vulvodynia remain poorly understood. Given the recognized association of the vaginal microbiota with various gynecologic disorders, there has been growing interest in exploring the potential role of the vaginal microbiota in the etiology of vulvodynia. This systematic review aims to evaluate the current literature on the association between the vaginal microbiota and vulvodynia. MATERIAL AND METHODS: A systematic search of multiple databases, including PubMed, Scopus, Web of Science, Cochrane Library, and Ovid MEDLINE, was conducted to identify relevant peer-reviewed studies up to May 12, 2023. The following search terms were used across these databases: "vulvodynia," "vestibulodynia," "vulvar vestibulitis," "microbiome," "microbiota," and "flora." RESULTS: A total of 8 case-control studies were included, the quality of which was assessed using the Newcastle-Ottawa Scale. Data extraction and synthesis were performed using a standardized protocol. In most studies, no major differences were found between the vaginal bacterial composition of women with vulvodynia and that of controls. No specific bacterial taxa were consistently associated with vulvodynia. The relationship between vaginal microbiota diversity and vulvodynia remains to be fully understood. CONCLUSIONS: The role of vaginal microbiota in vulvodynia, if any, remains unclear. Because of the cross-sectional nature of the included studies, it is not possible to make any causal inferences. Further research, using larger and more diverse study populations and advanced sequencing techniques, is necessary to gain a better understanding of the potential relationship between the vaginal microbiota and vulvodynia.

Features of the Vaginal and Vestibular Microbioma in Patients With Vestibulodynia: A Case-Control Study.

OBJECTIVE: Our objective was to determine the role of vaginal and/or vestibular microbiota disturbance as an associated factor of symptom characteristic of provoked vestibulodynia (PVD). STUDY DESIGN: In an observational case-control study, the bacterial microbiomes in the vagina and vestibule from 20 women with PVD and 18 healthy controls were compared using a 16S rRNA gene-based molecular analysis. Clinical data were recorded through a 0- to 10-point visual analog scale related to dyspareunia and vulvovaginal pain/burning. RESULTS: Comparative assessment of the bacterial taxa (cutoff ≥15%) revealed 105 genera in the vaginal samples of PVD patients and 113 genera in the vestibular samples. Similarly, 120 genera were detected in the vaginal samples and 151 in the vestibular samples of the control group. Bacterial complexity was higher in the vestibular samples than in vaginal samples in both groups, without statistically significant differences. The following 3 dominant taxonomic units were found: Lactobacillus, Gardnerella, and Atopobium in PVD patients and Lactobacillus, Gardnerella, and Bifidobacterium in the control group. Lactobacillus gasseri was dominant only in women with PVD, showing a significant correlation with burning/pain intensity and dyspareunia severity (0.255 and 0.357, respectively, p < .001). CONCLUSIONS: Our data suggest that bacterial communities in vaginal discharge are an important contributor to the vestibular microbiota. Lactobacillus gasseri may be an element of vulnerability toward the development of vaginal dysbiosis. We can postulate its association as a potential etiologic organism in some individuals, either by itself or in some combination with other trigger factors.

Severe Postmenopausal Genital Pain Treated Successfully With Prolonged Estrogen Therapy: A Case Series and Narrative Review.

OBJECTIVE: The aim of the study was to describe a debilitating postmenopausal condition of continuous burning genital pain that remitted with prolonged estrogen focused on the vulvar vestibule. MATERIALS AND METHODS: Postmenopausal patients with constant genital pain seen by the author in a specialty vulvar health clinic comprised an institutional review board-approved descriptive case series. Examinations to localize pain used 4% lidocaine topical solution. Each patient received estradiol nightly as vestibule crème or constantly by transdermal route and was followed by serial examinations and follow-up telephone contact. Statistical tests included Student t test, Fisher exact test, and Pearson correlation coefficient. RESULTS: Between 2008 and 2016, 16 women presented with constant genital pain that was partly or fully extinguishable with topical vestibular lidocaine, and their pain slowly responded to prolonged vestibule-directed estradiol therapy. The mean age was 66.8 years (± 11.2). The mean pain score was 5 (range = 2-10 on a 0-10 scale). Seven (44%) characterized their pain as debilitating, and 13 (81%) had accompanying urinary symptoms. In 9 patients (56%), ovaries had been removed before natural menopause at ages 27-50 years (mean = 39), followed by minimal or no estrogen therapy. Prolonged estrogen therapy eliminated constant pain in 69% and mitigated it in 31%. CONCLUSIONS: Information about this severe but remediable condition that is associated with lack of estrogen may guide specialists who are treating complex vulvar pain. The patients' clinical histories and therapeutic courses invite a review of estrogen receptor physiology related to urogenital pain conditions.

Vulvar vestibular effects of ospemifene: a pilot study.

The study aimed to assess the effects of ospemifene on vulvar vestibule in postmenopausal women with vulvar pain and dyspareunia. Fifty-five postmenopausal women used oral ospemifene 60 mg/d for 60 d. Symptoms of dryness, burning, and dyspareunia were evaluated on a 10 cm visual analog scale. Visual examination of the vulvar vestibule was also conducted. Patients also underwent current perception threshold (CPT) testing obtained from the vulvar vestibule. Fifty-five patients (94.6%) completed the treatment. Hot flashes were the most frequent adverse effects, but this led to a discontinuation of therapy in three patients (5.4%). After therapy, there was a statistically significant decrease from the baseline in the mean scores for dryness, burning, and dyspareunia and reduction of vestibular trophic score (baseline value of 11.2-4.2 after the therapy, p ≤ 002) and cotton swab test scores (2.81 compared with 1.25, p = .001). There was a difference in CPT values for all nerve fibers and more consistent for C fibers (-38% of sensitivity). These results confirm the efficacy of ospemifene on postmenopausal vestibular symptoms and signs; moreover, the drug was effective in normalizing vestibular innervation sensitivity.

Injury to Perineal Branch of Pudendal Nerve in Women: Outcome from Resection of the Perineal Branches.

Background This study describes outcomes from a new surgical approach to treat "anterior" pudendal nerve symptoms in women by resecting the perineal branches of the pudendal nerve (PBPN). Methods Sixteen consecutive female patients with pain in the labia, vestibule, and perineum, who had positive diagnostic pudendal nerve blocks from 2012 through 2015, are included. The PBPN were resected and implanted into the obturator internus muscle through a paralabial incision. The mean age at surgery was 49.5 years (standard deviation [SD] = 11.6 years) and the mean body mass index was 25.7 (SD = 5.8). Out of the 16 patients, mechanisms of injury were episiotomy in 5 (31%), athletic injury in 4 (25%), vulvar vestibulectomy in 5 (31%), and falls in 2 (13%). Of these 16 patients, 4 (25%) experienced urethral symptoms. Outcome measures included Female Sexual Function Index (FSFI), Vulvar Pain Functional Questionnaire (VQ), and Numeric Pain Rating Scale (NPRS). Results Fourteen patients reported their condition pre- and postoperatively. Mean postoperative follow-up was 15 months. The overall FSFI, and arousal, lubrication, orgasm, satisfaction, and pain domains significantly improved (p < 0.05). The VQ also significantly improved (p < 0.001) in 13 (93%) of 14 patients. The NPRS score decreased on average from 8 to 3 (p < 0.0001). All four patients with urethral symptoms were relieved of these symptoms. Conclusion Resection of the PBPN with implantation of the nerve into the obturator internus muscle significantly reduced pain and improved sexual function in women who sustained injury to the PBPN.

Effect of Vestibulectomy for Intractable Vulvodynia.

STUDY OBJECTIVE: To assess the effectiveness of vestibulectomy in treating vulvodynia for patients with inadequate response to vulvar care guidelines and medical management. DESIGN: Retrospective case series (Canadian Task Force classification II-2). PATIENTS: All patients who underwent a vestibulectomy from 2004 to 2013 for vulvodynia. INTERVENTIONS: All patients in this study underwent a vestibulectomy. MEASUREMENTS AND MAIN RESULTS: In this study we analyzed 31 patients' overall reported pain scores and Q-tip test scores before and after vestibulectomy. The efficacy of vestibulectomy on reduction of pain was then analyzed after surgical management. There was no significant difference in pain scores from initial visit compared with the last visit before vestibulectomy after vulvar care guidelines and medical management were initiated (p = .48-.94). However, mean subjective pain scores before and after vestibulectomy decreased by 67% (p < .001). Q-tip testing showed reductions of pain by 63% (p < .001) and 73% (p < .001) at the right and left Bartholin gland areas, respectively. There was approximately a 60% decrease of pain scored around the bilateral periurethral areas (p < .05). CONCLUSIONS: Vestibulectomy is an effective treatment for vulvodynia. For those with intractable pain, vestibulectomy is an appropriate next step after unsuccessful medical treatment. The surgery leads to a significant decrease in patients' pain scores, nearly eliminating it in most cases.

Elevated tissue levels of tumor necrosis factor-α in vulvar vestibulitis syndrome.

The purpose of this study was to compare levels of inflammatory cytokines, namely TNF-α, IL-1ß, and IL-1 receptor in women with vulvar vestibulitis syndrome (VVS) relative to levels in controls. The authors hypothesized that tissue concentrations of inflammatory cytokines would be elevated significantly in women with VVB compared to pain-free controls. The study population consisted of 15 women with strictly defined VVB in reproductive age and 13 age-matched women with no history of vulvodynia. For TNF-α, positive staining was observed in 40% of the samples from the study group and in 7.7% of the samples from the control group. The difference between the groups was statistically significant (p < 0.05). In conclusion, a limitation of the present study was the relatively small sam- ple size. However, the authors' intention was simply to propose that the local inflammation may be mediated by cytokines as TNF-α may rather than trying to single out a pathogenesis of VVS. The authors' findings of elevated TNF-α may suggest new therapeutic alternatives for VVS, as inhibiting cytokine synthesis or antagonism of the cytokine receptor.

Effectiveness of Two Transcutaneous Electrical Nerve Stimulation (TENS) Protocols in Women with Provoked Vestibulodynia: A Randomized Controlled Trial.

BACKGROUND: Vestibulodynia (VBD) is the most common form of vulvodynia. Because VBD is a pain disorder, transcutaneous electrical nerve stimulation (TENS) can be used as treatment. This study aims to evaluate the effects of two-parameter combinations (frequency and pulse duration) of TENS in reducing pain intensity and dyspareunia in VBD. METHODS: A randomized, double-blind, controlled trial was conducted to study the effect of two different electrical stimulation treatment regimens on women with VBD receiving domiciliary TENS. Outcomes were the mean change from baseline at 60 and 120 days of burning/pain and dyspareunia (VAS), Vulvar Pain Functional Questionnaire (V-Q), Female Sexual Functioning Index (FSFI) and vaginal electromyography measurements. RESULTS: A total of 78 subjects, 39 in each group, completed the trial. Patients in Groups 1 and 2 received a mean of 46.9 and 48.4 TENS sessions. By day 120, there was a 38.2% reduction in the burning/pain and a 52.1% reduction in the dyspareunia VAS scores in Group 1, as compared to 21.3% (p = 0.003) and 23.1% in Group 2 (p = 0.01), respectively. FSFI, V-Q, and muscle-strength measures also improved but were not statistically significant. CONCLUSIONS: Our findings showed the potential of TENS in the treatment of VBD.

Neuroproliferative dyspareunia in endometriosis and vestibulodynia.

INTRODUCTION: Endometriosis is a common cause of deep dyspareunia, while provoked vestibulodynia is a common cause of superficial dyspareunia. The etiology of dyspareunia in both conditions is multifactorial and may include the role of local nerve growth (neurogenesis or neuroproliferation) that sensitizes pelvic structures and leads to pain with contact. OBJECTIVES: To review the evidence for neuroproliferative dyspareunia in endometriosis and provoked vestibulodynia. METHODS: Narrative review. RESULTS: The pelvic peritoneum and vulvar vestibule receive somatic and autonomic innervation. Various markers have been utilized for nerve subtypes, including pan-neuronal markers and those specific for sensory and autonomic nerve fibers. The nerve growth factor family includes neurotrophic factors, such as nerve growth factor and brain-derived neurotrophic factor, and their receptors. Studies of endometriosis and provoked vestibulodynia have demonstrated the presence of nerve fibers around endometriosis epithelium/stroma in the pelvic peritoneum and within the vulvar vestibule. The number of nerve fibers is higher in these pain conditions as compared with control tissue. Nerve growth factor expression by endometriosis stroma and by immune cells in the vulvar vestibule may be involved in local neuroproliferation. Local inflammation is implicated in this neuroproliferation, with potential roles of interleukin 1ß and mast cells in both conditions. Several studies have shown a correlation between nerve fibers around endometriosis and dyspareunia severity, but studies are lacking in provoked vestibulodynia. There are several possible clinical ramifications of neuroproliferative dyspareunia in endometriosis and provoked vestibulodynia, in terms of history, examination, biopsy, and surgical and medical treatment. CONCLUSIONS: A neuroproliferative subtype of dyspareunia may be implicated in endometriosis and provoked vestibulodynia. Additional research is needed to validate this concept and to integrate it into clinical studies. Neuroproliferative pathways could serve as novel therapeutic targets for the treatment of dyspareunia in endometriosis and provoked vestibulodynia.

New Topical Therapy for Provoked Vestibulodynia: Improvement of Psychological and Sexual Well-Being.

Vulvodynia is a vulvar discomfort that occurs in the absence of any specific, clinically identifiable disorder. Few therapies have shown to be effective for the treatment of vulvodynia. In our recently published study, we tested a drug-free gel in women affected by vulvar vestibulitis. It is a cosmetic gel which acts locally without any metabolic, pharmacological or immunological effect. In order to further promote the validity of this new product, in this manuscript we analyzed the results obtained from the administration of four questionnaires in the same two groups of women affected by PVD and treated with a placebo and the new product. The questionnaires used: Female Sexual Function Index Scoring (FSFI), Female Sexual Distress Scale (FSDS), Hospital Anxiety and Depression Scale (HADS), and health-related quality of life measured by SF-36 (SF-36). The results obtained by this current analysis showed that the new gel has also proven benefits on women's quality of life and sexual function, including improvements in arousal, desire, orgasm and satisfaction.

Long-term well-being after surgical or conservative treatment of severe vulvar vestibulitis.

OBJECTIVE: To compare long-term well-being of women who needed surgery or did not need surgery in the treatment of severe vulvar vestibulitis syndrome. We also attempted to identify factors explaining differences in the treatment response. DESIGN: An observational case-control study. SETTING: University Hospital Vulva clinic. POPULATION: Sixty-six women diagnosed with severe vulvar vestibulitis and treated initially by conservative management during 1994-2005. Thirty-nine women did not respond and underwent posterior vestibulectomy and 27 were managed without surgery. METHODS: Baseline patient characteristics, degree of dyspareunia, and details of management were collected from hospital charts. At the follow-up visit current dyspareunia, sexual well-being, somatic and mental health, and social support were analyzed. Vestibular tenderness was measured by swab-touch test. MAIN OUTCOME MEASURES: Visual analogue scale for dyspareunia, sexual well-being, vestibular tenderness, and overall patient satisfaction at follow-up. RESULTS: Dyspareunia decreased significantly in both groups. The visual analogue scale decreased 66.7% in the surgery group and 78.1% in the conservative treatment group (p= 0.407). Posterior swab-touch test was negative more frequently after vestibulectomy. Long-term sexual well-being did not differ between the two groups. Overall, 89% of the women in both groups were satisfied with the treatment. Women with atopic skin problems were less likely to need surgery (odds ratio 0.2; 95% confidence interval 0.1-0.7). CONCLUSION: Women with severe vulvar vestibulitis syndrome who do not respond to conservative management achieve good long-term well-being and decrease of dyspareunia by posterior vestibulectomy. The response is comparable to that achieved by conservative management among women who do not need surgery.

Attributions about pain as predictors of psychological symptomatology, sexual function, and dyadic adjustment in women with vestibulodynia.

The present study examined whether attributions for vulvo-vaginal pain predicted pain intensity, sexual function, as well as psychological and dyadic adjustment in women with vestibulodynia. Women with vestibulodynia (N = 77) completed measures of attributions, pain, psychological distress, sexual functioning, and dyadic adjustment. They also took part in a structured interview and a gynaecological examination for diagnostic purposes. Attributions are represented by: (1) internality (personal responsibility) or externality (cause lies in an external situation); (2) globality (entire life affected by the problem) or specificity (problem affecting only a specific situation); (3) stability (problem will still remain in the future) or instability (weak probability that the problem will be maintained with time); and (4) partner responsibility (partner responsible or not for the problem). Results indicated that attributions were not significantly correlated with pain outcomes. However, after controlling for pain intensity and relationship duration, internal attributions predicted higher dyadic adjustment, both global and stable attributions predicted lower dyadic adjustment and higher psychological distress, whereas global attributions also predicted increased sexual impairment. Findings suggest that cognitive factors, such as attributions, may be related to psychological distress, sexual functioning, and dyadic adjustment in women with vestibulodynia. Results also highlight the importance of adhering to a biopsychosocial perspective focusing on pain reduction, sexual rehabilitation, and relationship enhancement in the treatment of dyspareunia.

Long-term follow up of posterior vestibulectomy for treating vulvar vestibulitis.

OBJECTIVE: To evaluate the safety and the effectiveness of posterior vestibulectomy in the treatment of vulvar vestibulitis syndrome. DESIGN: A retrospective cohort study. SETTING: University Hospital, tertiary referral center. POPULATION: Seventy women treated by posterior vestibulectomy for severe vulvar vestibulitis syndrome during 1995-2007 at the Department of Obstetrics and Gynecology, University Hospital, Helsinki. METHODS: All operated women were invited to a long-term follow-up study. Patient characteristics, baseline visual analog scale (VAS) for dyspareunia and data from the postoperative period were collected. Of the 70 women, 57 attended the follow-up visit including face-to-face interview, gynecological examination with swab-touch test for vestibular tenderness, current VAS score for dyspareunia and McCoy questionnaire for sexual problems. MAIN OUTCOME MEASURES: Short-term and long-term complication rates, dyspareunia by VAS score, vestibular tenderness, sexual problem index and overall patient satisfaction. RESULTS: Ninety-one per cent were satisfied with the outcome. The VAS for dyspareunia decreased from a median of 9 to 3 (66.7% decrease; p<0.001). Posterior vestibular tenderness was absent in 34 patients (64.2%). Six (8.6%) patients developed postoperative bleeding and 11 (15.7%) mild wound infection. Bartholin's cysts occurred in four (5.7%) patients. CONCLUSIONS: Posterior vestibulectomy is effective and safe in the treatment of severe vulvar vestibulitis syndrome and provides long-term patient satisfaction.

Perineal canal: a special entity of anorectal malformations in Vietnam.

PURPOSE: We report our clinical experience with the perineal canal and suggest the management. MATERIALS AND METHODS: Retrospective chart review of patients with perineal canal were classified by lesion characteristics into Group I: active perineal inflammation, Group II: vulvar excoriation and Group III: no active inflammation. Group III patients underwent primary surgical repair. Group I and II patients underwent repair after medical management. The fistula was repaired by the modified Tsuchida's technique consisting of an anterior anopullthrough and excision of the fistula tract (reverse order). RESULTS: Between September 1999 and August 2003, we treated 120 cases of perineal canal. Group I, II and III consisted of 74, 12 and 34 patients, respectively. In two patients of Group I (2.7%), the fistula tract spontaneously closed. The remaining 118 patients were surgically treated with the modified Tsuchida's technique. Recurrences were similar between patients treated with colostomy (1/28 or 3.6%) versus without colostomy (3/90 or 3.0%), as well as between patients initially treated with primary repair (3/102 or 2.9%) versus patients undergoing reoperation with redo repair (1/16 or 6.25%). CONCLUSIONS: With proper initial medical treatment, the perineal canal could be repaired successfully in one stage with the modified Tsuchida's technique.

Surgical treatment of vulvar vestibulitis: a review.

Vulvar vestibulitis syndrome, a subset of vulvodynia, is a complex pain syndrome. It causes severe dyspareunia and affects mainly young women. The etiology is unknown and no uniformly effective treatment exists. Surgery has been considered as 'the last resort' in the management of patients not responding to conservative treatment modalities. For this review, all studies of surgical treatment of vulvar vestibulitis were evaluated. We describe the evolution of vestibulectomy techniques through the years. Our aim was also to find out whether any surgical technique is better than others providing better patient satisfaction and lower complication rates. We conclude that surgical technique as such plays a relatively small role. Surgery seems to be effective. However, lack of randomized trials and insufficient data on complication rates must be emphasized.

The histopathological results of vestibulectomy specimens in localized provoked vulvodynia in Turkey.

INTRODUCTION: Localized Provoked Vulvodynia (LPV) is a gynecological disease that is difficult to manage. Despite the wide spectrum of pathophysiological mechanisms and treatment modalities, there is limited success in the management of this disease. Surgical treatment is usually performed as the last resort. We aimed to investigate the histopathological results of 38 women with LPV who underwent surgical vestibulectomy. METHODS: of the 55 women that were diagnosed with LPV and underwent vulvar vestibulectomy, 38 patients with complete histopathological results were included in this retrospective study. RESULTS: in 14 patients, the pathological reports revealed Low-Grade Squamous Intraepithelial Lesions (LGSIL) (36.8%) whereas for 21 cases (55.2%), the findings were concordant with vestibulitis. The remaining three patients (7.8%) were diagnosed with lichen simplex chronicus. CONCLUSION: the presence of LGSIL in the surgical specimens of LPV cases is noteworthy. In this group of patients, surgical excision may contribute to the prevention of progression into high-grade lesions. The relationship between Human Papilloma Virus (HPV) infections and LPV should be further investigated.

Sacral neuromodulation in the treatment of vulvar vestibulitis syndrome.

BACKGROUND: Vulvar vestibular syndrome is a chronic pain syndrome that typically results in pain and irritation of the vulvar vestibule and has few effective options for treatment. CASE: A 42-year-old woman presented with symptoms consistent with chronic vulvar vestibular syndrome that was refractory to multiple attempted therapies. The patient was offered sacral neuromodulation for treatment. She underwent a standard two-phase surgical implantation with good result at 2 years postimplantation. CONCLUSION: Sacral neuromodulation was shown to be a valid treatment option for this patient and resulted in excellent patient satisfaction at 2-year follow-up. Although the exact mechanism of action is unknown, sacral neuromodulation may be a viable option for the management of chronic pain syndromes of the vulva and vagina.

Polymorphism in a gene coding for the inflammasome component NALP3 and recurrent vulvovaginal candidiasis in women with vulvar vestibulitis syndrome.

OBJECTIVE: Patients with vulvar vestibulitis syndrome (VVS) and control subjects were tested for a polymorphism in the gene coding for the NALP3 component of inflammasomes, cytoplasmic structures regulating interleukin (IL)-1beta production. STUDY DESIGN: DNA from 143 women with VVS and 182 control women were tested for a length polymorphism in intron 4 of the gene (CIAS1) that codes for NALP3. Vestibular tissue was examined for NALP3 expression. Whole blood cultures were tested for Candida albicans-induced IL-1beta production. RESULTS: The allele 12 frequency was higher in control subjects than in the patients with VVS (P = .02). Among patients with VVS and a self-reported history of recurrent vulvovaginal candidiasis (RVVC), the allele 7 frequency was 43.9% as compared with 30.8% in patients with no history of RVVC and 26.9% in control women (P = .035 vs other patients and .001 vs control subjects). NALP3 was identified in vestibular tissue. C albicans-induced IL-1beta production was reduced in samples from women with the 7,7 genotype (P = .030). CONCLUSION: Polymorphism in the CIAS1 gene may play a central role in the triggering of VVS in a subset of patients.