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.

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.

Vulvodynia: A practical guide in treatment strategies.

Vulvodynia is a debilitating condition characterized by chronic vulvar pain, with a detrimental impact on the patient's overall quality of life. Its etiology is multifactorial, but still in the process of being clearly outlined. Vulvodynia is not a single entity. It is a heterogeneous condition characterized by multiple triggers, making it challenging to define a reference standard for its treatment. In this manuscript we selected all articles including the following key criteria: "vulvodynia". The primary outcomes observed included the resolution of chronic pelvic pain, dyspareunia and sexual satisfaction, psychological well-being, and overall quality of life. Most pharmacologic treatments require further evidence to be recommended. On the other hand, non-pharmacologic approaches such as psychotherapy, physical therapy, and surgery have received stronger support. This review summarizes pros and cons of adopting available treatments. Multimodal approaches should be introduced to improve patient outcomes. Further investigations are warranted to improve patients' quality of life.

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 "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.

Fractional Pixel CO2 laser treatment for decubitus ulcer in advanced pelvic organ prolapse: a case report.

OBJECTIVE: Cervicovaginal decubitus ulceration is a complication of advanced pelvic organ prolapse that is very difficult to manage. Here, we report on the effectiveness of fractional CO2 laser treatment for a wide decubitus ulcer over an apical vaginal vault prolapse. METHODS: We report a case of a postmenopausal woman with a wide decubitus ulcer over a vaginal vault prolapse. A fractional microablative CO2 Pixel laser system (Alma Lasers, Cesarea, Israel), equipped with an appropriate probe for the vulva, was used to treat the ulceration of a 78-year-old patient across three laser sessions with 30-day intervals. RESULTS: A significant improvement in the decubitus ulcer was noted in a check-up held 2 months after the final laser session, with approximately 95% wound healing observed. No side effects were reported during or after the laser therapy. CONCLUSIONS: This case demonstrates that fractional Pixel CO2 laser treatment is a viable option for managing decubitus ulcers before definitive surgery in postmenopausal women with advanced pelvic organ prolapse.

Vulvar pain: The revealing scenario of leading comorbidities in 1183 cases.

OBJECTIVES: This study set out to investigate the epidemiological characteristics and comorbidities of chronic vulvar pain. Secondary goals were to identify the preferred approaches for managing vulvodynia in Italy. STUDY DESIGN: A cross-sectional study (the VuNet -Vulvodynia Network project) was performed in consecutive female patients with chronic vulvar pain attending 21 Italian medical centers (public hospitals, university clinics and private outpatient services) in the period December 2016 to November 2018. Study data were entered by healthcare professionals in a special web-based medical record system (PRIDE- Progetto Rete Italiana Dolore vulvarE). These data covered epidemiological aspects, demographic characteristics, obstetric and gynecological history, presence and duration of current and/or past symptoms, associated disorders, details of physical examination and treatment approaches. RESULTS: A total of 1183 subjects with a diagnosis of chronic vulvar pain were included in the study. The main reason for consultation was superficial dyspareunia, present in 64.2 % of the women. 43.4 % of the sample reported comorbid sexual disorders (of desire in 22.1 % and arousal in 21.3 %). 48.3 % of the patients reported prolonged pain lasting between one and five years. Factors associated with vulvar pain included a relatively high family history of diabetes mellitus (father = 8.6 %; mother = 8.4 %), recurrent vulvovaginal candidiasis (32 %), and urinary tract infections (37.4 %: recurrent cystitis in 19.5 % and post-coital cystitis in 17.9 %). Irritable bowel syndrome (28 %), constipation (23.5 %), headache (25.7 %: migraine in 18.0 % and menstrual headache in 7.7 %), allergies (17.5 %: food allergies in 10.1 %, respiratory allergies in 7.4 %), anxiety (15.0 %), dyschezia (11.7 %), invalidating dysmenorrhea/endometriosis (11.1 %), and major depression (7.6 %) were also reported. Vestibulodynia was diagnosed in 837 of the 1183 patients (70.8 %) and generalized vulvodynia in 323 (27.3 %). Notably, 69.1 % of the patients stated that previous therapies had not changed their pain. CONCLUSIONS: The diagnoses of vestibulodynia and vulvodynia must be considered in patients with chronic vulvar pain. The VuNet study contributes to a more comprehensive reading of the predisposing, precipitating and maintaining factors that contribute to vulvar pain, and of the key comorbidities.

Characterization of female intimate hygiene practices and vulvar health: A randomized double-blind controlled trial.

BACKGROUND: Inappropriate feminine hygiene practices are related to vulvar unpleasant symptoms (such as skin changes, lesions, burning, pruritus, fissures, and dyspareunia). AIMS: We assessed the daily use effects of intimate cleansers on vulvar skin by comparing two specific products for intimate care: Saugella Hydraserum (SIS), based on natural extracts, and a standard product based on lactic acid, such as Lactacyd Feminine Hygiene (LTC). Forty healthy women were enrolled in this double-blind controlled study. METHODS: After randomization, the cleansers were used twice daily for 30 days. The hydration level was determined using the Corneometer® CM 825, the pH using the Skin-pH-Meter PH 905® and the sebum level using the Sebumeter SM815® . Measurements were performed at baseline and on day 30 on the labia majora and labia minora. RESULTS: Both cleansers showed a reduction in the hydration level, but this was much less evident in the SIS group (-6.3% SIS vs -23,7% LTC). The pH values of the SIS group were lower than those of the LTC group, especially on the labia minora (5.27 ± 0.08 and 5.6 ± 0.1, respectively, P = .025). The sebum increased in both groups, but in the LTC group, it was higher on the labia majora (+96.2% vs +46.8%, respectively, P = .003), while on the labia minora, it was higher in the SIS group (+24.7% vs +17.1%, respectively P = NS). CONCLUSIONS: Both cleansers tested showed high performance for safety and tolerability on vulvar skin, but SIS showed better efficacy than LTC on some parameters.

Clinical profile of women with vulvar and vaginal atrophy who are not candidates for local vaginal estrogen therapy.

Vulvar and vaginal atrophy (VVA) is a chronic medical condition in postmenopausal women, which is predominantly due to a permanent cessation of ovarian estrogen production. Current available treatment options for VVA are over-the-counter (OTC) symptomatic relief products or local estrogen therapy (LET) aiming to treat this underlying atrophic condition. Recent surveys indicated that these products decrease sexual spontaneity, are messy and indiscrete. Ospemifene is an oral daily drug, which has proven to treat vaginal dryness and dyspareunia effectively. However, despite the comparable efficacy of ospemifene versus placebo to estrogen versus placebo, ospemifene is currently indicated for women, who are not candidates for LET. It is up to the gynecologist to make an appropriate therapeutic decision. There are potential candidates who have not been considered for ospemifene and yet would benefit from this treatment, such as breast cancer survivors, or patients unable to perform or that have problems performing vaginal insertion/application of estrogen based treatments, such as women that suffer from prolapse. Likewise, a patient's concern for hormone treatment safety, treatment regimens complexity or cross contamination with their partner are potential issues to consider when prescribing treatment for VVA in order to provide the best therapeutic option for patients who are generally not compliant with their current therapy.

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.

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.