Differentially Regulated miRNAs and Their Related Molecular Pathways in Lichen Sclerosus.

Lichen sclerosus (LS) is a chronic inflammatory skin disorder with unknown pathogenesis. The aberrant expression of microRNAs (miRNAs) is considered to exert a crucial role in LS. We used the next-generation sequencing technology (RNASeq) for miRNA profiling and Ingenuity Pathway Analysis (IPA) for molecular network analysis. We performed qRT-PCR, miRNA transfection and Matrigel assays for functional studies. We identified a total of 170 differentially expressed miRNAs between female LS and matched adjacent normal tissue using RNASeq, with 119 upregulated and 51 downregulated. Bioinformatics analysis revealed molecular networks that may shed light on the pathogenesis of LS. We verified the expression of a set of miRNAs that are related to autoimmunity, such as upregulated miR-326, miR-142-5p, miR-155 and downregulated miR-664a-3p and miR-181a-3p in LS tissue compared to the matched adjacent normal tissue. The differentially expressed miRNAs were also verified in blood samples from LS patients compared to healthy female volunteers. Functional studies demonstrated that a forced expression of miR-142-5p in human dermal fibroblast PCS-201-010 cells resulted in decreased cell proliferation and migration. These findings suggest that differentially expressed miRNAs may play an important role in LS pathogenesis; therefore, they could serve as biomarkers for LS management.

Fractionated Carbon Dioxide Laser for the Treatment of Vulvar Lichen Sclerosus: A Randomized Controlled Trial.

OBJECTIVE: To estimate the efficacy of fractionated carbon dioxide (CO2) laser therapy for vulvar lichen sclerosus. METHODS: We conducted a prospective, double-blind, randomized, sham-controlled, trial conducted in a clinic specializing in vulvar disorders. The study participants were 40 women with active vulvar lichen sclerosus confirmed with biopsy who were abstaining from topical and systemic treatments for at least 4 weeks before enrollment. Women were randomized in a 1:1 ratio to receive either five sham laser treatments or five fractionated CO2 treatments in a 24-week period. Study participants, treating clinicians, and the evaluating pathologist were blinded. The primary endpoint was the change in the histopathology scale score between pretreatment and posttreatment biopsies. We estimated 20 per group for 80% power to detect a 40% reduction in the histopathology scale score with up to 10% attrition. A secondary endpoint was the change in the validated CSS (Clinical Scoring System for Vulvar Lichen Sclerosus). RESULTS: From November 2018 to June 2020, 40 women were randomized to participate in the trial, and 37 women (19 fractionated CO2, 18 sham) were included in an intention-to-treat (ITT) analysis. Three women were excluded from the ITT analysis because they did not have posttreatment biopsies and, therefore, a posttreatment histopathology scale score could not be obtained. There was a 0.20 reduction (improvement) in histopathology scale score from baseline in the active treatment group (95% CI -1.1, 0.80, P=.74) and a 0.1 increase from baseline in the sham treatment group (95% CI -0.90, 1.0, P=.91). The change in histopathology scale score between the active and sham arm was not statistically significant (95% CI -1.14, 1.06, P=.76). CONCLUSION: Fractionated CO2 is not an effective monotherapy treatment for vulvar lichen sclerosus. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03665584. FUNDING SOURCE: Additional funding for this study was supplied by El.En Group, Florence, Italy, the manufacturer of the laser used in this study. In addition, El.En Group supplied the laser used in the study.

Exploring Pain-Related Anxiety and Depression in Female Patients With Provoked Vulvodynia With Associated Overactive Pelvic Floor Muscle Dysfunction.

INTRODUCTION: Vulvodynia is a chronic pain condition with potential associated factors, including musculoskeletal and psychosocial components. AIM: This study explores the prevalence of pain-related anxiety and depression in women with provoked vestibulodynia with associated overactive pelvic floor muscle dysfunction (PVD-PFD). METHODS: A retrospective chart review of 352 women presenting to 2 urban vulvovaginal specialty clinics over the course of a year was conducted. Women presenting for initial evaluation completed validated questionnaires for pain-related anxiety and depression. Women who completed these questionnaires with a diagnosis of PVD-PFD independently confirmed by a women's health physical therapist were included in analysis. Information on previously attempted treatments was gathered. MAIN OUTCOME MEASURES: Pain-related anxiety was measured with the Pain Anxiety Symptoms Scale-20 and depression with the Patient Health Questionnaire 8. RESULTS: Of 79 women with confirmed PVD-PFD, 22% met criteria for pain-related anxiety alone, 4% for depression alone, and 27% for both pain-related anxiety and depression, with a significant association between anxiety and depression (χ2 (1) = 21.44, P < .0005, phi = 0.521). There was also a significant association between anxiety and/or depression and whether prior treatment was attempted (χ2 (2) = 6.81, P = .03, phi = 0.294). CONCLUSION: The study found that 49% of women with PVD-PFD experienced pain-related anxiety, with or without depression. In addition, there was a statistically significant association between attempts at prior treatment and greater pain-related anxiety and depression. This is the first study to report a rate of pain-related anxiety specifically in women with PVD-PFD. These findings are consistent with studies showing elevated pain-related anxiety in other chronic musculoskeletal conditions, including lower back pain and fibromyalgia. Govind V, Krapf JM, Mitchell L, et al. Exploring Pain-Related Anxiety and Depression in Female Patients With Provoked Vulvodynia With Associated Overactive Pelvic Floor Muscle Dysfunction. J Sex Med 2020;8:517-524.

Vulvar Lichen Sclerosus: Current Perspectives.

Vulvar lichen sclerosus (LS) is a chronic, inflammatory dermatosis that may lead to scarring of the vulva and sexual dysfunction. LS affects women of all ages and often goes unrecognized and underreported. Uncertainty continues to exist around its pathogenesis, histologic diagnosis, and treatment. However, there have been great advances in our understanding of autoimmunogenic targets in disease formation and progression. In addition, there has been recent investigation of potential non-steroid-based treatments, including platelet-rich plasma therapy and energy-based modalities such as the fractional CO2 laser, photodynamic therapy, and high intensity focused ultrasound. Refinement of surgical techniques for restoring vulvar anatomy and treating clitoral phimosis, introital stenosis, and vulvar granuloma fissuratum is leading to improved patient outcomes. This review summarizes current perspectives on the pathogenesis, symptomatology, diagnosis, and treatment for vulvar lichen sclerosus.

Spironolactone May be a Cause of Hormonally Associated Vestibulodynia and Female Sexual Arousal Disorder.

BACKGROUND: Although spironolactone is an effective treatment for androgen-mediated cutaneous disorders, the potential sexual side-effects are poorly documented in current literature. AIM: The purpose of this study was to provide clinical evidence that spironolactone may be a cause of hormonally associated vestibulodynia and female sexual arousal disorder. METHODS: A database search of a vulvar disorders clinic revealed 7 cases in which spironolactone may have caused or contributed to dyspareunia and decreased arousal. In all cases, the patients stopped taking spironolactone and used a compounded estradiol 0.01%/testosterone 0.1% gel to the vestibule twice daily. 2 cases are discussed to further illustrate these previously unreported side effects. OUTCOMES: Improvement in sexual function was determined after treatment. RESULTS: Examination of women taking spironolactone who presented with the complaints of introital dyspareunia revealed vulvar vestibular atrophy and tenderness, especially at the glandular ostia. After stopping spironolactone and applying a topical estrogen/testosterone gel to the vestibule, all women had significant improvement in their vulvar atrophy, resolution of their dyspareunia, and improved sexual arousal. CLINICAL IMPLICATIONS: Use of spironolactone may be a cause of hormonally associated vestibulodynia and female sexual arousal disorder. STRENGTHS AND LIMITATIONS: The influence of spironolactone on vulvar health and sexual function is poorly documented in the medical literature. The strength of this paper is that it examines the potential deleterious side effects of this medication on female sexual function. However, the most significant limitation of this case series is that it was not a prospective, controlled study. CONCLUSIONS: Although treatment of androgen-mediated cutaneous disorders is warranted, medical providers should be aware of the potential sexual side effects of this anti-androgenic medication. Mitchell L, Govind V, Barela K, et al. Spironolactone May be a Cause of Hormonally Associated Vestibulodynia and Female Sexual Arousal Disorder. J Sex Med 2019;16:1481-1483.

Cervical Ectropion May Be a Cause of Desquamative Inflammatory Vaginitis.

Desquamative inflammatory vaginitis is a poorly understood chronic vaginitis with an unknown etiology. Symptoms of desquamative inflammatory vaginitis include copious yellowish discharge, vulvovaginal discomfort, and dyspareunia. Cervical ectropion, the presence of glandular columnar cells on the ectocervix, has not been reported as a cause of desquamative inflammatory vaginitis. Although cervical ectropion can be a normal clinical finding, it has been reported to cause leukorrhea, metrorrhagia, dyspareunia, and vulvovaginal irritation. Patients with cervical ectropion and desquamative inflammatory vaginitis are frequently misdiagnosed with candidiasis or bacterial vaginosis and repeatedly treated without resolution of symptoms. We report the case of a 34-year-old woman with a 4-year history of profuse yellowish discharge and dyspareunia. Upon presentation, her symptoms and laboratory results met the criteria for desquamative inflammatory vaginitis, but the standard treatments did not provide long-lasting relief. As a last resort, cryotherapy (cryosurgery) of her cervix was performed for treatment of her cervical ectropion, which provided complete resolution of her symptoms. Mitchell L, King M, Brillhart H, Goldstein A. Cervical Ectropion May Be a Cause of Desquamative Inflammatory Vaginitis. Sex Med 2017;5:e212-e214.