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.

Coital pain in the elderly: could a low dose estriol gel thrill the vulvar vestibule?

OBJECTIVE: The aim of this study was to evaluate the effectiveness of the application of 0.005% estriol gel to the vulvar vestibule in the management of postmenopausal dyspareunia. STUDY DESIGN: Postmenopausal women with dyspareunia were enrolled in this study. Patients were instructed to use a fingertip to apply 0.25g of vaginal gel containing 25µg of estriol to the vulvar vestibule daily for three weeks and then twice weekly for up to 12 weeks. RESULTS: Assessment of symptoms (dyspareunia and cotton swab test) and signs of vestibular atrophy were performed, and changes between baseline and weeks 3 and 12 were assessed. Adverse events were recorded. A total of 63 women were included. Of the 63, 59 (93.6%) completed the 12-week treatment period, and four dropped out for vestibular burning. Dyspareunia improved or was cured (score ≤1) by week 12 in 81.4% of patients. The patients also showed a statistically significant reduction in vestibular atrophy and cotton swab test at the end of treatment. CONCLUSIONS: Application of 0.005% estriol gel to the vulvar vestibule is effective in correcting menopausal coital pain. This suggests that reduction in sensory vestibular innervation sensitivity is likely to play a pivotal role in the relief of dyspareunia. One limitation of this study is the limited follow-up, but the therapy may be continued for as long as the patients are distressed by their symptoms without estrogen intervention.

Primary and Secondary Provoked Vestibulodynia: A Review of Overlapping and Distinct Factors.

INTRODUCTION: A common subtype of vulvodynia is provoked vestibulodynia (PVD), characterized by severe pain upon contact to the vaginal entrance. Some researchers have further delineated the PVD group based on pain onset (primary vs secondary PVD, referred to as PVD1 and PVD2, respectively). AIM: This study aims to review available evidence regarding sociodemographic variables, pain characteristics, medical history and examination findings, quantitative sensory testing, genetic markers, psychosocial/sexual/relationship function, treatment outcome, and brain imaging in women with PVD1 and PVD2. METHODS: All available data related to PVD1 and PVD2 were reviewed. MAIN OUTCOME MEASURES: There is mixed evidence supporting the assumption that women with PVD1 fare worse on all variables investigated. RESULTS: The review indicated that although women with PVD1 seem to fare worse on many variables examined (eg, pain severity, genetic markers), many studies also indicated no significant group differences or-less commonly-that women with PVD2 fare worse on some variables (eg, sexual function). CONCLUSION: Although it has been suggested that different pathophysiologic processes are involved in the development and maintenance of PVD1 and PVD2, the data reviewed were mixed. While most studies indicated that women with PVD1 have higher pain intensity, higher sensitivity, more genetic influence, more evidence of inflammation, lower successful treatment outcomes, and different neural activation patterns and structural findings, these results were not consistently reported. In addition, the data for subgroup differences in psychosocial, sexual, and relationship variables were not convincing. A more precise definition of primary and secondary PVD is needed, and importantly, prospective, longitudinal studies are essential for clarifying any differences within these PVD subgroups.

Increased gray matter density in young women with chronic vulvar pain.

Provoked vestibulodynia (PVD) is a common form of chronic vulvar pain with unknown aetiology. Central pain regulatory mechanisms have been suggested to be disrupted in PVD, and consequently, PVD may be associated with anatomical changes in pain modulatory brain areas. Here, we compared total gray matter volumes and regional gray matter densities between 14 medication-free young women with relatively short-standing PVD (1 to 9 yrs) and 14 control subjects using whole brain voxel-based morphometry (VBM). VBM revealed that PVD subjects had significantly higher gray matter densities in pain modulatory and stress-related areas, i.e. the parahippocampal gyrus/hippocampus and basal ganglia (globus pallidus, caudate nucleus, and substantia nigra). In several of these regions, gray matter was related to clinical symptoms, namely lowered pain thresholds and increased pain catastrophizing scores. No region showed decreased gray matter density in the PVD group. These results point at the morphological alterations in supra-spinal pain modulatory circuitry, which might contribute to the clinical symptoms of patients with PVD. Previous VBM studies in older subjects with a longstanding chronic pain condition have demonstrated gray matter decreases in similar areas. We therefore speculate that gray matter density might increase in young pain patients with short disease duration and decrease in older subjects with longstanding disease, similarly to some psychiatric conditions, in which bi-directional changes of gray matter have been observed.

Somatization and psychological distress among women with vulvar vestibulitis syndrome.

OBJECTIVE: To investigate the distribution of psychological characteristics and pain reporting among women with vulvar vestibulitis syndrome (VVS). METHODS: In this exploratory study, 109 women with VVS completed a battery of questionnaires to assess pain with intercourse and psychological characteristics (e.g. somatization, anxiety, distress). The distribution of these characteristics was compared, first with a conventional binary classification schema (primary and secondary) and subsequently with a 3-category schema (primary, latent primary, secondary). RESULTS: Severity of pain with intercourse did not differ among the subgroups using either classification schema. Women with primary VVS consistently showed higher levels of somatization, anxiety, and distress compared with those with secondary VVS. Using a 3-tiered classification system, we found no difference between latent primary diagnosis and the other 2 groups (primary and secondary). CONCLUSION: This study highlights the critical need for research on subtype definition and the role of psychological factors in VVS.

Umbilical hypersensitivity in women with primary vestibulodynia.

OBJECTIVE: To provide evidence that primary vestibulodynia (PV) is a congenital defect in tissue derived from the primitive urogenital sinus. STUDY DESIGN: Twenty-two women with PV, 16 with secondary vestibulodynia (SV) and 8 controls were included in this study. Subjects underwent a complete history and physical examination, including assessment with a vulvalgesiometer to measure the sensory and pain detection thresholds in the vulvar vestibule, deltoid and umbilicus. RESULTS: The median vestibular sensitivity was 5 g in the PV group and 10 g in the SV group (p= 0.77). The median umbilical pain thresholds for the PV, SV and control groups were 115, 675 and 500 g, respectively. Women with PV displayed a significantly higher level of umbilical sensitivity (a substantially lower pain threshold) compared with women with SV and the control group (p = 0.0001 and 0.002, respectively). There was no difference in umbilical sensitivity between the SV and control groups. CONCLUSION: Because both the umbilicus and vulvar vestibule are derived from primitive urogenital sinus, this suggests that women with PV may have a congenital abnormality in urogenital - sinus-derived epithelium.

The treatment of provoked vestibulodynia: a critical review.

OBJECTIVE: To carry out a critical review of published studies concerning the treatment of provoked vestibulodynia. METHODS: MEDLINE, PsycINFO, and Cochrane were used to identify treatment studies published between January 1996 and December 2006. All studies published in English that dealt specifically with the treatment of provoked vestibulodynia were included in the review regardless of their methodological quality. Thirty-eight treatment studies were thus examined in the present paper. RESULTS: Since 1996, surgical treatment has received somewhat less empirical attention. Nevertheless, it still boasts the best success rates, which range from 61% to 94%. More studies have focused on medical treatments, yielding success rates varying between 13% and 67%. Behavioral treatments have been the least studied, although 35% to 83% of patients benefit from them. Despite these interesting results, only 5 of the 38 treatment studies reviewed are randomized clinical trials. Furthermore, the majority of studies have several methodological weaknesses, such as the absence of (1) control or placebo group, (2) double-blind evaluation, (3) pretreatment pain evaluation, and (4) validated measures of pain and sexual functioning. DISCUSSION: On the basis of the results of the reviewed prospective studies and the randomized clinical trials, vestibulectomy is the most efficacious treatment to date. Though some medical treatments seem little effective, others appear promising and should be investigated further, as is the case with behavioral treatments. Additional randomized clinical trials are necessary to confirm the efficacy of surgery and validate nonsurgical treatments for provoked vestibulodynia.

Involvement of heparanase in the pathogenesis of localized vulvodynia.

Recently, we have shown that vestibular hyperinnervation and the presence of 8 or more mast cells in a 10 x 10 microscopic field can be used as diagnostic criteria in localized vulvodynia (vulvar vestibulitis). We have also documented that degranulation of mast cells occurs in these cases. The present study further examines the characteristics of vestibular hyperinnervation and mast cell function in localized vulvodynia to elucidate if the 2 processes-hyperinnervation and mast cell increase and degranulation-are related. We examined vestibular tissue from 7 women aged 18 to 48 with severe localized vulvodynia and from 7 healthy control women. Parallel sections were stained by Giemsa and then immunostained for CD117 and heparanase. Nerve fibers that expressed protein gene product 9.5 were examined. Tissues from women with localized vulvodynia documented a significant increase in vestibular mast cells, subepithelial heparanase activity, and intraepithelial hyperinnervation compared with healthy women. This is the first documentation of heparanase activity in localized vulvodynia. Heparanase, which is degranulated from mast cells, is capable of degrading the vestibular stroma and epithelial basement membrane, thus permitting stromal proliferation and intraepithelial extension of nerve fibers, as seen in the present study. The hyperinnervation has been thought to cause the vestibular hyperesthesia distinctive of localized vulvodynia.