Spotlight on Compounded Bioidentical Hormones.

BACKGROUND: The role of hormonal replacement therapy in menopause is under debate. The premature closure of the Women's Health Initiative (WHI) study in 2002 is still a source of concern among treating physicians. OBJECTIVES: The interest in alternatives to conventional hormone therapy has significantly increased. The adoption of personalized steroid hormone galenic preparations, formulated by compounding pharmacies, has recently spread. METHODS: In June 2023, an extensive literature search was conducted by different authors to identify relevant studies in various databases (MEDLINE, Embase, PubMed, and Cochrane). The studies that met the inclusion and exclusion criteria were further analyzed, and relevant data were extracted and analyzed for each paper. Any discrepancies between the investigators were resolved through a consensus approach. OUTCOMES: The primary outcomes observed included the clinical utility of CBHT. This study reviewed the current evidence on the utility of compounded bioidentical hormones, concluding that improving knowledge and awareness of bioidentical hormones is necessary to consider their use in clinical practice. CONCLUSION AND OUTLOOK: These formulations might provide effective options to best tailor therapies to each patient.

The Role of ß1 Integrin/CD29 as a Potential Prognostic Factor for the Risk of Progression to Cervical Carcinoma in HPV-Associated Lesions.

Background and Objectives: Available evidence reports the overexpression of ß1 integrin in dysplastic rather than normal cervical tissue. We aimed to evaluate the involvement of ß1 (CD29) integrin in the progressive pathogenesis of cervical intraepithelial neoplasia (CIN). Materials and Methods: From January 2019 to December 2021, we prospectively enrolled women undergoing a colposcopy with a cervical biopsy for abnormal cervical cytology and/or undefined cytology with a positive HPV DNA test and women with relapsing cervical inflammatory disorders. Based on the histopathological results, women were divided into four groups: group A (CIN1), group B (CIN2), group C (CIN3), and group D (no CIN diagnosis) as a control group. Subsequently, cytofluorimetry and immunohistochemical analysis (based on the identified positive cell ratios as follows: ≤10%, negative; 10-25%, 1+ (weak); 25-50%, 2+ (medium); ≥50%, and 3+ (high)) for ß1 integrin were carried out. Results: In total, 154 women were included. The average fluorescence intensity in the four groups was 2.35 ± 1.37, 2.73 ± 1.56, 3.09 ± 1.56, and 2.13 ± 1.25 UA from groups A to D, respectively; this figure was significantly different for CIN3 (group C) women relative to the other groups (p = 0.0132). Higher ß1 integrin/CD29 concentrations in the CIN groups with HR-HPV 16 and 18 were also detected (p = 0.0292, 0.0367, and 0.0357 respectively for CIN3, CIN2, and CIN1). Immunohistochemistry analysis showed higher results for the CIN3 group compared to controls and all the other groups (p < 0.001). Conclusions: ß1/CD29 integrin expression increased with CIN grade, and it was significantly higher in CIN3 lesions. This could be used as a promising screening tool to identify women prone to developing high-grade cervical lesions. However, additional evidence is needed to strengthen these findings.

Safety and efficacy of fractional CO2 laser treatment to the vestibule: a randomized, double-blind, sham-controlled, prospective 3-site clinical study in women with vestibular pain.

BACKGROUND: Data are limited regarding fractional CO2 laser as a nonhormonal treatment for vestibular pain. AIM: We sought to perform what is, to our knowledge, the first multisite prospective randomized, double-blind, sham-controlled clinical trial to assess the safety and efficacy of fractional CO2 laser treatment to the vestibule in women with vestibular pain. METHODS: Subjects (n = 70) meeting inclusion/exclusion criteria at each of 3 sites were randomized 2:1 to active or sham (zero energy) fractional CO2 laser treatment using the vestibular probe (SmartXide2 V2LR - MonaLisa Touch, DEKA, Florence, Italy). Subjects in each treatment arm received 3 treatments 4 weeks apart. At the initial follow-up (week 12), subjects were unblinded and those initially assigned to sham started active treatment. OUTCOMES: Outcome measures included changes from baseline in sexual activity diaries and scores for the Vulvoscopic Genital Tissue Appearance Scale (VGTA), vestibular cotton-tipped swab testing, McGill Pain Questionnaire, Female Sexual Function Index (FSFI), Female Sexual Distress Scale-Revised (FSDS-R), and the O'Leary-Sant voiding and pain indices, the Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI). RESULTS: After active treatment, VGTA scores significantly improved in 5 parameters. Pain associated with cotton-tipped swab testing was significantly reduced at weeks 4 through 16 (mean change from baseline -0.64 [95% CI, -0.79 to -0.50] and -1.31 [95% CI, -1.46 to -1.16], respectively). FSFI pain domain scores improved significantly at weeks 12 and 16 (mean change from baseline 0.925 [95% CI, 0.10-1.75] and 1.22 [95% CI, 0.40-2.05], respectively). FSFI total scores increased significantly at weeks 12 and 16 (mean change from baseline 6.24 [95% CI, 2.64-9.85] and 4.96 [95% CI, 1.36-8.57], respectively). FSDS-R scores decreased significantly at weeks 12 and 16 (mean change from baseline -5.84 [95% CI, -8.80 to -2.87] and -9.15 [95% CI, -12.11 to -6.18], respectively). ICSI scores decreased significantly at weeks 12 and 16 (mean change from baseline -0.91 [95% CI, -1.65 to -0.18] and -0.754 [95% CI, -1.49 to -0.02], respectively). ICPI scores decreased significantly at week 16 (mean change from baseline -0.99 [95% CI, -1.63 to -0.34]). In contrast, there were no significant changes in outcomes in the sham arm. No serious adverse events occurred. CLINICAL IMPLICATIONS: Fractional CO2 laser treatment in women with vestibular pain resulted in improvement from baseline in multiple key outcome measures of vestibular health. STRENGTHS AND LIMITATIONS: Strengths of the study were that it was a multisite prospective randomized double-blind, sham-controlled clinical trial that included multiple measures related to vestibular pain and sexual function. Limitations were the nonvalidated primary outcome measure and limited study cohort. CONCLUSION: Fractional CO2 laser therapy is a safe and effective nonhormonal treatment for vestibular pain.

The impact of combined contraceptive vaginal ring on vaginal environment: an observational, longitudinal study.

PURPOSE: To assess the relationship between combined contraceptive vaginal ring (CVR) and vaginal microbiome using 16S rRNA gene sequencing. MATERIALS AND METHODS: We enrolled 20 women for 8 weeks in an open-label study using CVR (NuvaRing®) that delivered 15 mcg ethinylestradiol and 120 mcg etonogestrel daily. The vaginal microbiome was assessed at baseline and after 2 months by sequencing the 16S rRNA genes amplified from the total genomic DNA isolated from the sample. RESULTS: Bacterial distribution richness and equity did not significantly change after 2 months, and the dominant bacterial strain was Lactobacillus crispatus. Only one woman with a history of vestibulodynia and recurrent vulvovaginitis showed an increase in bacterial biodiversity, with a switch to the relative abundance of anaerobic bacteria. CONCLUSIONS: Our results suggest that CVR does not adversely affect the composition and structure of the vaginal microbiome. However, special care should be taken in patients with a history of vestibulodynia and/or recurrent vulvovaginal infections.

Contraceptive vaginal ring does not adversely affect vaginal microbiome except in the case of recurrent vulvovaginal infections or vestibulodynia.

The role of female intimate hygiene practices in the management of vulvovaginal candidiasis: A randomized, controlled open-label trial.

In this multicenter, observational, controlled open-label trial, researchers randomized 200 women with vulvovaginal candidiasis (VVC) to: Group 1, 6-days clotrimazole 2% vaginal cream once-daily plus 15-days concomitant acid pH thymol and zinc-containing cleansing wash (SaugellaActi3) twice-daily; Group 2, 6-days clotrimazole treatment alone. In both groups, pruritus and burning VAS scores improved from baseline at Days 6, 10 and 15. On Day 10 and Day 15, the pruritus score was significantly lower in Group 1 versus Group 2 (P <0.005 at both timepoints), suggesting acid pH thymol and zinc-containing cleansing wash ameliorates VVC-associated pruritus as part of a female hygiene regimen.

The "CIV Classification," a New Proposal for the Architectural Grading of Vulvar Lichen Sclerosus.

OBJECTIVES: The purpose of this cross-sectional study was to prepare a reliable and easy-to-use architectural classification for vulvar lichen sclerosus (VLS) aimed at defining the morphological patterns of this condition. MATERIALS AND METHODS: An expert panel composed by 7 physicians with expertise in clinical care of vulvar conditions outlined the architectural criteria for the definition of VLS severity (phimosis of the clitoris, involvement of the interlabial sulci, narrowing of the vulvar introitus), identifying 5 grades to build up a classification. Thirteen physicians with 2-30 years expertise in vulvar diseases (nonexpert group) were asked to evaluate 3-5 pictures from 137 patients. Each physician individually assigned a grade to each case, according to the previously mentioned criteria. Interrater reliability was analyzed by means of intraclass correlation coefficient (ICC). The reliability concerning the 2 classifications of each rater was analyzed by means of κ statistic. Intraobserver and interobserver reliability in vivo was analyzed by means of κ index. RESULTS: This study provides a new classification of VLS, based on defined anatomical criteria and graded into mutually exclusive progressive classes.The ICC analysis showed a substantial interrater reliability of the classification, ICC = 0.89 (0.87-0.91), both in the expert panel and in the nonexpert group (ICC = 0.92 and 0.87, respectively). An "almost perfect" intraobserver and interobserver reliability was achieved among physicians in vivo (κ = 0.93). CONCLUSIONS: Our classification showed a high reliability. It is easy to use, and it can be applied in clinical practice and eventually, in the evaluation of regenerative and cosmetic surgery.

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.

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.

Thymol, eugenol and lactobacilli in a medical device for the treatment of bacterial vaginosis and vulvovaginal candidiasis.

The aim of this non-interventional, observational, multicentre, open-label study was to assess the effectiveness of a vaginal gel containing extracts of Thymus vulgaris and Eugenia caryophyllus in conjunction with two specific lactobacilli strains (Lactobacillus fermentum LF10 and Lactobacillus plantarum LP02) specifically formulated in slow-release vaginal capsules, in treating bacterial vaginosis (BV), vulvovaginal candidiasis (VVC) or recurrent vulvovaginal candidiasis disease (RVVC) [Estromineral Probiogel (EPB) in Italy, or Saugella Probiogel; Meda Pharma - Mylan Group]. There was a statistically significant improvement in pruritus, burning, vulvovaginal oedema and erythema, dyspareunia and vaginal secretions in all diagnostic groups. At the end of the study, the microbiological evaluation was normal in 80.0% of cases with BV, 62.5% of cases with VVC and 100.0% with RVVC. The clinical data allow EPB to be recommended in the acute treatment of VVC and BV, suggesting that EPB is a useful maintenance treatment if there are recurrent episodes. Controlled studies are needed to confirm the efficacy of EPB in the treatment of recurrences and to identify the most appropriate dosage regimen.

Alpha Lipoic Acid Plus Omega-3 Fatty Acids for Vestibulodynia Associated With Painful Bladder Syndrome.

OBJECTIVE: This study assessed the effectiveness of alpha lipoic acid (ALA) plus omega-3 polyunsaturated fatty acids (n-3 PUFAs) in combination with amitriptyline therapy in patients with vestibulodynia/painful bladder syndrome (VBD/PBS). METHODS: Women with VBD/PBS were randomly assigned to receive amitriptyline or amitriptyline plus a commercially available preparation (ALAnerv Age; Alfa Wassermann, Bologna, Italy) containing, in 2 capsules, ALA 600 mg plus docosahexaenoic acid 250 mg and eicosapentaenoic acid 16.67 mg. Symptoms of burning and pain were assessed using a 10-cm visual analog scale and the short form of the McGill-Melzack Pain Questionnaire. RESULTS: Among 84 women who were randomized, the mean ± standard deviation dose of amitriptyline was 21.7 ± 6.6 mg/day, without statistical difference between the two groups. Pain, as assessed using both the pain rating index of the visual analog scale and the short-form McGill Pain Questionnaire, decreased significantly in both trial groups, with a greater effect seen with the addition of ALA and n-3 PUFAs. The addition of ALA/n-3 PUFAs to amitriptyline treatment was also associated with improvements in dyspareunia and pelvic floor muscle tone. The overall incidence of adverse events was low, and none led to treatment discontinuation. CONCLUSIONS: The addition of ALA/n-3 PUFAs to amitriptyline treatment in patients with VBD/PBS appears to improve outcomes and may allow for a lower dosage of amitriptyline, which may lead to fewer adverse effects.

Fractional CO2 Laser Treatment of the Vestibule for Patients with Vestibulodynia and Genitourinary Syndrome of Menopause: A Pilot Study.

INTRODUCTION: Chronic vulvar pain and burning remains one of the most perplexing problems faced by practicing gynecologists. AIM: To evaluate the effectiveness and safety of the application of micro-ablative fractional CO2 laser to the vulvar vestibule in the management of patients with vulvar pain from vestibulodynia or genitourinary syndrome of menopause. METHODS: Patients (N = 70) underwent fractional micro-ablative CO2 laser treatment for vestibular pain plus vestibulodynia (n = 37) or genitourinary syndrome of menopause (n = 33). Inclusion criteria were the existence of vestibular atrophic changes and the absence of moderate or severe pelvic floor hypertonic dysfunction. MAIN OUTCOME MEASURES: A visual analog scale of pain and the Marinoff score of dyspareunia were chosen to evaluate improvement. Grading of vestibular health also was quantified using a four-point scoring system (0 = no atrophy, 3 = severe atrophy). Data were collected at baseline, at weeks 4, 8, and 12, and 4 months after the final treatment. RESULTS: For visual analog scale and dyspareunia scoring and for the overall vestibular health index scoring, statistically significant improvement was noted after three sessions of vestibular fractional CO2 laser treatment. Improvement gradually increased throughout the study period and was maintained through the 4-month follow-up visit. There was no statistically significant difference in outcomes between the two study groups. No adverse events from fractional CO2 laser treatment were noted. Overall, 67.6% of patients stated significant improvement from the laser procedure. CONCLUSION: This preliminary case series showed encouraging results using fractional CO2 laser treatment of the vestibule in women with vestibulodynia and genitourinary syndrome of menopause.

Vulvar lichen sclerosus: a comparison of the short-term topical application of clobetasol dipropionate 0.05% versus mometasone furoate 0.1%.

OBJECTIVE: To compare the efficacy of the short-term application of clobetasol propionate 0.05% (CLB) and mometasone furoate 0.05% (MMF) in the treatment of vulvar lichen sclerosus (VLS). STUDY DESIGN: This study was a retrospective review of 96 women who were diagnosed with lichen sclerosus with a follow-up of at least 1 year. Of these 96 women, 47 were treated with the topical application of CLB and 49 were treated with the topical application of MMF. All patients received treatment for 8 weeks. The drug was administered once daily for 4 weeks and then twice weekly for another 4 weeks in combination with a moisturizing cream that was continued as maintenance therapy. Subsequently, a topical steroid was applied on an as-needed basis if symptoms recurred. Follow-up visits were scheduled at 3, 6, and 12 months. The primary endpoint was the clinical response of the patients. RESULTS: A mean of 77.3% of the patients were defined as responders at the 12-month observation, without any significant difference between the 2 treatment groups (CLB mean 73% vs MMF mean 81.6%, p = .2). A pronounced improvement in itching was observed after 3 months of treatment in the MMF group (p = .04), whereas the other symptoms were not significantly different between the 2 groups. CONCLUSIONS: This study indicates that CLB 0.05% and MMF 0.1% in a short protocol regimen are effective, safe, and reliable treatments for VLS, with no significant difference between the 2 steroids in their efficacy. However, a moisturizing cream should be an integral part of the treatment.

Can Lactobacillus fermentum LF10 and Lactobacillus acidophilus LA02 in a slow-release vaginal product be useful for prevention of recurrent vulvovaginal candidiasis?: A clinical study.

OBJECTIVE: To assess the effectiveness of the association of 2 specific strains, Lactobacillus fermentum LF10 (DSM 19187) and Lactobacillus acidophilus LA02 (DSM 21717), specifically formulated in slow-release effervescent tablets, in patients with recurrent vulvovaginal candidiasis. STUDY DESIGN: The study was a clinical trial of 58 women diagnosed with recurrent VVC (≥4 culture-confirmed episodes in a 12-mo period). All patients were given 200 mg of fluconazole orally as an induction dose for 3 alternate days during the first treatment week. Afterward, the patients were given a new product formulated in slow-release vaginal tablets containing at least 0.4 billion live cells of each of lactobacillus L. fermentum LF10 and L. acidophilus LA02 (first phase of the prophylactic period), on alternate days for 10 consecutive nights. Patients who were still free of symptoms were given 1 vaginal tablet every week for the next 10 weeks (second phase of the prophylactic period). Patients asymptomatic after the total duration of the observation phase (7 mo) were considered as responders. RESULTS: During the second 10-week prophylactic phase, 49 of 57 (86.0%) patients remained free of clinical recurrence, whereas symptomatic VVC occurred in 8 patients (14.0%). During the 7-month follow-up, 42 patients of 49 (85.7%) were symptom free at the end of the protocol, whereas clinical recurrences occurred in 7 women (14.3%). Overall, 42 of 58 women enrolled in the study (72.4%) experienced no clinical recurrence throughout the 7-month observation phase (responders). CONCLUSIONS: This study strengthens the evidence supporting the use of specific lactobacilli with well-demonstrated activities associated with the creation and maintenance of a vaginal biofilm that hinders the persistence of an infection caused by Candida.

Treatment of Prepubertal Labial Adhesions with Topical Estriol + Testosterone: A Case Report.

BACKGROUND: Labial adhesions, a frequent gynecological condition in prepubertal girls, occur when the labia minora adhere along the midline. The prevailing hypothesis about their etiology suggests that labial adhesion may occur when the delicate and non-estrogenized labia minora undergo an inflammatory response, triggered by exposure to an irritant environment. Therefore, conservative treatment involves the application of topical estrogen or betamethasone cream. The role of androgens has not been considered yet in the pathophysiology or therapy of this condition. However, some studies have shown that androgen receptors are prevalent in the labia minora and vulvar vestibule. CASE SUMMARY: We present the case of a 29-month-old girl with symptomatic labial adhesions. She was first ineffectively treated with topical estriol, and then she was treated with a galenic cream containing both estriol and testosterone with complete recovery and without side-effects. CONCLUSIONS: Both androgens and estrogens play a significant role in maintaining the physiological trophic state of the vulva and vagina, even during childhood. Topical estriol+testosterone could be considered an alternative treatment for prepubertal labial adhesions refractory to standard topical therapy.

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.

Ospemifene and vulvovaginal atrophy: an update of the clinical profile for post-menopausal women.

INTRODUCTION: The demand for effective and safe treatments of genitourinary syndrome (GSM) in post-menopausal women (PMW) is growing. Published data on the efficacy and safety of ospemifene (OSP) prompt an updated literature review to enlighten possible improvements in the GSM treatment. AREA COVERED: We searched articles published in English from 2010 to 2023 through Medline (PubMed) and Embase databases with Boolean terms: OSP, PMW, GSM, endometrium, breast cancer, cardiometabolic syndrome, bone metabolism, adherence to treatment, and patient satisfaction. We selected randomized controlled trials (RCTs) and observational and cross-sectional studies and completed the search manually. EXPERT OPINION: Of the 157 retrieved records, 25 primary studies met the inclusion criteria (15 regarding efficacy and safety, two for additional effects, and four for adherence and satisfaction with the OSP treatment). Seven RCTs involved nearly 5,000 patients, 10 out of 18 prospective observational studies 563, and six retrospective analyses 356,439. Evidence of OSP treatment in PMW with GSM relies on RCTs and remarkable real-world data. The 25 primary studies showcased the high clinical response to symptoms, the favorable safety profile of OSP with very few adverse events, a neutral impact on the endometrium, breast, bone, and thrombosis, and the possible improvement of cardiovascular risk factors.

POLARIS: efficacy and safety of a vaginal medical device in recurrent bacterial vaginosis-a multicenter, open-label, non-controlled, study with 10 months of follow-up.

OBJECTIVE: Recurrent bacterial vaginosis (RBV) after antibiotic treatment has relapse rates of 35% within 3 months and 60% within 12 months. A medical device containing polycarbophil, lauryl glucoside, and glycerides (PLGG) inhibits bacterial growth and has mucoadhesive properties. This study examined the efficacy of the device in women with RBV. METHODS: This post-market clinical follow-up study comprised two phases. The first phase was an interventional, open-label, non-controlled, multicenter study enrolling 56 women. The second phase was an observational 10-month follow-up without treatment. RESULTS: After three cycles of PLGG treatment, recurrence was identified in 8 of 54 evaluable patients (14.81%). A positive effect on lactobacilli in the vaginal secretions was observed in 26 of 39 patients (66.67%). Among 35 patients observed after stopping PLGG treatment, one case of RBV (2.86%) was observed after 4 months, and an additional six cases (17.14%) were observed after 10 ± 2 months. Therefore, no recurrence was evidenced in 12 subjects (34.28%) at the end of the study. CONCLUSION: The use of PLGG vaginal ovules in the treatment of BV reduces the rate of recurrence and apparently produces a positive effect on the vaginal microbiota.

Vestibulodynia: synergy between palmitoylethanolamide + transpolydatin and transcutaneous electrical nerve stimulation.

OBJECTIVE: The study aimed to assess the effect of palmitoylethanolamide + transpolydatin combination in patients with vestibulodynia undergoing transcutaneous electrical nerve stimulation (TENS) therapy and to confirm the effectiveness of TENS also in a domiciliary protocol. The study is based on the premise that palmitoylethanolamide + transpolydatin combination may contribute to a down-regulation of mast cell hyperactivity, which is believed to be responsible for the proliferation and sprouting of vestibular pain fibers and the associated hyperalgesia and allodynia. MATERIALS AND METHODS: Twenty women with vestibulodynia were randomly assigned to receive oral palmitoylethanolamide (PEA) 400 mg and transpolydatin 40 mg or placebo, twice daily for 60 days. All patients underwent TENS therapy in a self-administered home protocol. Visual analogue scale (VAS), Marinoff score for dyspareunia, and current perception threshold obtained from the vulvar vestibule were assessed at baseline and at the end of treatment. RESULTS: The patients received a mean of 26.7 TENS sessions. All scores in the 2 groups improved significantly, although the level of improvement was similar between the groups (VAS, p < .57; dyspareunia, p < .38). Nevertheless, the analysis of regression of symptoms related to the duration of disease revealed the therapy to be more effective when PEA + transpolydatin is included in cases with more recent disease onset, as compared with the placebo group (PEA: VAS, p < .01; dyspareunia, p < .01) (placebo: VAS, p = nonsignificant; dyspareunia, p = nonsignificant). CONCLUSIONS: This study confirms that TENS is of significant benefit in the management of vestibulodynia, also in a home environment. PEA + transpolydatin can be a value-added treatment adjunct when the onset of vestibulodynia is more recent or when the disease relapses.

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.

New medical device coating mouth gel for temporary relief of teething symptoms: a pilot randomized, open-label, controlled study.

BACKGROUND: This study verified the feasibility of the monthly recruitment rate, tested the Face, Legs, Activity, Cry and Consolability Pain Assessment Tool (FLACC) for pain in infants and collected preliminary efficacy and safety data of a new proprietary oral gel formulation of high-molecular-weight hyaluronan (HMWHA) for the relief of teething. Results will support the design a future main trial vs. local anesthetic, that is currently the only clinically proven pain reliever. METHODS: This was a pilot, randomized, controlled, multicenter, open-label, and parallel-group trial. It was performed in two Romanian clinics recruiting infants from 3 to 36 months. Teething diagnosis was based on a minimum of three symptoms such as: local pain, swelling, erythema, hyper-salivation, and depth characteristics of unerupted tooth. Absence of subcutaneous mucosal laceration was also required. The children were assigned either to HMWHA (HABPX V 3.3, Bioplax Ltd, Wallington, UK), or to standard drug (Dentinox®-Gel N; Dentinox, Berlin, Germany) and treated for 7 consecutive days. Investigators recorded the primary endpoints: swelling, redness and pain (by FLACC method), on days 0, 3 and 7. Changes in crying, mouth spasms, salivation, local pain, swelling, and redness were the secondary endpoints, recorded daily by the parents, on diary cards. Tolerability was assessed on day 14, too. RESULTS: Twenty-seven Infants were allocated in HMWHA, and 30 in standard drug. Enrolment rate was 9 patients/month/site. A significant reduction for HMWHA group was evidenced in pain, swelling (from day 0 to 7, P=0.034 between groups), redness (from day 0 to 3, P=0.045 and from day 0 to 7, P<0.001 between groups) and confirmed by the parents' diary records. Pain measurements obtained by FLACC method are consistent with the data belonging to other parameters. Investigator's global assessment of performance was in favor of the HMWHA (P<0.005). Only two patients, both belonging to standard drug group, experienced adverse events (fever, not related to treatment) and dropped out of the study. CONCLUSIONS: The results solve the feasibility questions and clearly evidence the performance of HABPX V 3.3 in teething symptoms, exceeding the objectives of a simple pilot trial to some extent. Coating oral gels containing HMWHA could be a therapeutic solution for both parents and physicians in managing the irritation and pain resulting from tooth eruption in children.