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BackgroundApproximately 26% of adult women in the United States suffer from female sexual arousal disorder (FSAD), yet little has been done to compare the experience of FSAD in pre- and postmenopausal women, which is critical to enhance the current understanding of FSAD and inform the development and assessment of treatment options for these patient populations.AimTo explore the experience of condition-associated symptoms and the relative importance of FSAD symptoms, including their severity, bother, and impact, on participants’ health-related quality of life (HRQoL) in pre- and postmenopausal women with FSAD.MethodsIn-depth, qualitative, semistructured concept elicitation interviews were conducted with premenopausal (n = 23) and postmenopausal (n = 13) women who were clinically diagnosed with FSAD by a trained sexual medicine clinician. All interviews were audio recorded and transcribed verbatim by a professional transcription company. Thematic analysis was performed with the assistance of NVivo qualitative analysis software.OutcomesOutcomes included qualitative interview data about FSAD symptoms and HRQoL, as well as a comparison between pre- and postmenopausal populations.ResultsThe most frequently reported symptom in both cohorts was “inability or difficulty with orgasm” (premenopausal, n = 21; postmenopausal, n = 13). The symptom that premenopausal women most desired to have treated was lubrication, and for postmenopausal women, it was a lack of lubrication or wetness and loss of feeling/sensation. In total, 21 of 23 premenopausal women and all 13 postmenopausal women reported a lack of feeling or sensation in the genitals. The most frequently reported HRQoL impact in both groups was decreased confidence.Clinical ImplicationsResults from this study suggest that the manifestation and experience of FSAD are similar in pre- and postmenopausal women and that the unmet need for an FSAD treatment in the postmenopausal population is just as great as that of the premenopausal population.Strengths and LimitationsThis study involved in-depth qualitative interviews with a relatively small group of women (N = 36) recruited from only 5 study sites across the United States.ConclusionThe analysis of qualitative data from the concept elicitation interviews revealed a substantial physical and emotional burden of FSAD, underscoring the need for Food and Drug Administration–approved treatment options for pre- and postmenopausal women with FSAD.

Topical corticosteroids are often utilized as the first-line treatment for vulvar lichen sclerosus (VLS). However, there is wide variability in dosing regimens, as well as a lack of consensus on maintenance dosing. Available guidelines on dosing frequency and regimen continuation for VLS are based on clinical expert opinion and do not necessarily reflect the pharmacokinetics of topical corticosteroids. Over the past few decades, there have been many advances in the techniques used to measure the local and systemic absorption of topical corticosteroids. These techniques have led to a greater understanding of the pharmacokinetics and bioavailabilities of these medications. However, it is not clear how this new information has been applied in evaluating dosing regimens and commonly cited risks when considering short- and long-term use in different vulvar dermatoses. This purpose of this review is to evaluate the available evidence on pharmacokinetics, absorption rates, and concentration levels of topical corticosteroids in lesional and nonlesional skin. Additionally, the evidence regarding commonly cited risks of topical corticosteroid use, including dermal thinning, adrenal suppression, systemic immunosuppression, and tachyphylaxis are reviewed. Differences in the effects of topical corticosteroids on the varied tissues of the vulva are specifically explored. Finally, these considerations are applied to evaluate the current treatment guidelines for VLS to provide direction in determining an evidenced-based dosing regimen and to inform future research in this area. Mautz TT, Krapf JM, Goldstein AT. Topical Corticosteroids in the Treatment of Vulvar Lichen Sclerosus: A Review of Pharmacokinetics and Recommended Dosing Frequencies. Sex Med Rev 2021;XX:XXX-XXX.

OBJECTIVE This systematic review aimed to present the available literature on plasma cell vulvitis (PCV), a relatively uncommon form of inflammatory vulvovaginal dermatitis. MATERIALS AND METHODS A literature search was performed in PubMed, Science Direct, and Google Scholar using the following key words: "plasma cell vulvitis," "Zoon vulvitis," and "vulvitis circumscripta plasmacellularis." Specific variables were assessed in each article, including patient age, menopausal status, comorbidities, presenting symptoms, symptom duration, histological description, treatment, and treatment response. RESULTS Thirty-nine articles met inclusion criteria, including 38 case reports and 1 observational study, with a total of 96 cases of PCV reported. The mean age of diagnosis was 52.9 years, with an age range of 8-76 years. Most common presenting symptoms included pruritis and vaginal discomfort, with average duration of symptoms 28.2 months (range = 2 months to 10 years). All reports demonstrated subepithelial plasma cell infiltrate on histology. Five percent of PCV cases reported concomitant autoimmune conditions and 6% sexually transmitted infections. Most common treatment modalities included topical corticosteroids (n = 41), tacrolimus (n = 6), and imiquimod (n = 6). In 53 reported outcomes, 88.7% of patients had resolution of symptoms with treatment. CONCLUSIONS Clinical research is needed to better determine the diagnostic criteria and to assess the efficacy of treatment options for PCV.

Background Persistent genital arousal disorder (PGAD), a condition of unwanted, unremitting sensations of genital arousal, is associated with a significant, negative psychosocial impact that may include emotional lability, catastrophization, and suicidal ideation. Despite being first reported in 2001, PGAD remains poorly understood. Aim To characterize this complex condition more accurately, review the epidemiology and pathophysiology, and provide new nomenclature and guidance for evidence-based management. Methods A panel of experts reviewed pertinent literature, discussed research and clinical experience, and used a modified Delphi method to reach consensus concerning nomenclature, etiology, and associated factors. Levels of evidence and grades of recommendation were assigned for diagnosis and treatment. Outcomes The nomenclature of PGAD was broadened to include genito-pelvic dysesthesia (GPD), and a new biopsychosocial diagnostic and treatment algorithm for PGAD/GPD was developed. Results The panel recognized that the term PGAD does not fully characterize the constellation of GPD symptoms experienced by patients. Therefore, the more inclusive term PGAD/GPD was adopted, which maintains the primacy of the distressing arousal symptoms and acknowledges associated bothersome GPD. While there are diverse biopsychosocial contributors, there is a common underlying neurologic basis attributable to spontaneous intense activity of the genito-pelvic region represented in the somatosensory cortex and its projections. A process of care diagnostic and treatment strategy was developed to guide the clinician, whenever possible, by localizing the symptoms as originating in any of five regions: (i) end organ, (ii) pelvis/perineum, (iii) cauda equina, (iv) spinal cord, and (v) brain. Psychological treatment strategies were considered critical and should be performed in conjunction with medical strategies. Pharmaceutical interventions may be used based on their site and mechanism of action to reduce patients’ symptoms and the associated bother and distress. Clinical Implications The process of care for PGAD/GPD uses a personalized, biopsychosocial approach for diagnosis and treatment. Strengths and Limitations Strengths and Limitations: Strengths include characterization of the condition by consensus, analysis, and recommendation of a new nomenclature and a rational basis for diagnosis and treatment. Future investigations into etiology and treatment outcomes are recommended. The main limitations are the dearth of knowledge concerning this condition and that the current literature consists primarily of case reports and expert opinion. Conclusion We provide, for the first time, an expert consensus review of the epidemiology and pathophysiology and the development of a new nomenclature and rational algorithm for management of this extremely distressing sexual health condition that may be more prevalent than previously recognized. Goldstein I, Komisaruk BR, Pukall CF, et al. International Society for the Study of Women’s Sexual Health (ISSWSH) Review of Epidemiology and Pathophysiology, and a Consensus Nomenclature and Process of Care for the Management of Persistent Genital Arousal Disorder/Genito-Pelvic Dysesthesia (PGAD/GPD). J Sex Med 2021;18:665–697.

Presenting symptoms of vulvar lichen sclerosus (LS) specific to premenopausal women are not well reported in the literature and may differ from those in postmenopausal women. This study aimed to characterize the presentation of vulvar LS among premenopausal women.An observational web-based study was conducted in premenopausal women with biopsy-confirmed vulvar LS between the ages of 18-50 years. Participants completed a 28-question survey evaluating characteristics of symptoms, timing of diagnosis, alternate diagnoses, and presence of concomitant autoimmune conditions.Of the 956 responses received, 503 met inclusion criteria of biopsy-confirmed LS and premenopausal status. Average age of symptom onset was 27 years, and average age of diagnosis was 32 years, with a 4-year delay in diagnosis. Symptoms most present were dyspareunia (68%) and tearing with intercourse or vaginal insertion (63%). Symptoms that affect the individual most were also dyspareunia (44%) and tearing with intercourse or vaginal insertion (39%). Symptoms that most frequently prompted patients to seek medical attention were dyspareunia (35%), pruritus (31%) and tearing with intercourse or vaginal insertion (26%). Most common skin changes included hypopigmentation (81%), vulvar fissures (72%), and labial resorption (60%), with fissures affecting the individual the most (48%). Sixty-six percent of the respondents initially received an alternative diagnosis, most commonly vulvovaginal yeast infection (49%). Hypothyroidism was the most common concurrent autoimmune condition (10%).Vulvar LS affects premenopausal women, commonly presenting with dyspareunia and tearing with intercourse. This condition should be considered and evaluated in premenopausal women presenting with vulvar symptoms and sexual pain.

Objective Rural Yunnan Province is one of the most ethnically, culturally, and religiously diverse regions in China. The majority of its women have never been screened for cervical cancer. It is not known whether women would feel comfortable and ultimately even prefer using a human papillomavirus (HPV) self-swabbing method. Methods In a 6-day period, 3,600 women were taught the role of HPV in cervical cancer. They were then given self-swabbing instructions. After obtaining their specimens, 600 women were interviewed about their experience with HPV self-testing. The women were of the Yi, Hui, Dai, and Han ethnicities. Results The overwhelming majority of the women surveyed understood the self-sampling instructions (588/600, 98%) and felt comfortable carrying out the self-sampling procedure (584/600, 97%). Significantly more women (389/600, 64.8%) preferred self-sampling to having the provider (211/600, 35.2%) obtain the sample (χ2 = 105.61, p < .05). Women who preferred self-sampling did so primarily because they felt capable of obtaining the specimens (n = 80) or that it was a more convenient way to be tested (n = 79). The medical expertise of the provider (n = 74) and concerns over the accuracy of the test (n = 88) shifted some women's preference toward a provider-obtained sample. Conclusions There are 400+ million Chinese women who have never had a cervical cancer screening. Self-testing has the potential to significantly increase the number of women tested. Despite the diversity of the women screened, the majority felt comfortable self-sampling and preferred self-swabbing to provider testing.

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.

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.

Introduction Cervical cancer is the leading cause of cancer deaths in women in the developing world. New technologies have been developed to allow for more rapid, cost-effective, and sensitive cervical cancer screening and treatment. Aim The aim of this study was to describe methods for detection and treatment of human papillomavirus (HPV), cervical dysplasia (CD), and cervical cancer. New technologies and updated screening strategies will be emphasized. Methods A literature search was conducted using PubMed to identify publications relevant to the subject. Main Outcome Measure Sensitivity and cost-effectiveness of new cervical cancer screening methods were the main outcome measures. Results HPV and cervical cancer have a significant global impact. Research and innovations related to detection and treatment are key in reducing their burden worldwide. Conclusion Screening a woman for HPV and CD can dramatically decrease her risk of dying from cervical cancer. New, rapid, low-cost, HPV testing can allow for high-volume screening for the approximately 1.5 billion women who have never been screened. HPV screening can then be combined with high resolution digital colposcopy to detect CD. In the near future, these colposcopic images will be interpreted by artificial intelligence software. Detected lesions can then be treated easily and effectively with thermocoagulation. This see-and-treat model is a sensitive, efficient, and low-cost vision for the future.

Acute genital ulcers (AGU), known as Lipschütz ulcers, are painful vulvar ulcers typically affecting non-sexually active girls and women. AGU have been associated with viral infections, namely, Epstein-Barr virus (EBV). Here, we describe a case of AGU in the setting of SARS-CoV-2 in a non-sexually active adolescent girl hospitalised for pain control and urinary retention, who failed a course of oral corticosteroids and then improved with colchicine. Testing for herpes simplex virus, EBV and Behcet’s syndrome were all negative. Testing for SARS-CoV-2 was positive. COVID-19 increases cytokines such as tumour necrosis factor alpha, which has been shown to affect endothelial cell adhesion and neutrophil chemotaxis, leading to aphthosis.

Background We propose an economical cervical screening research and implementation strategy designed to take into account the typically slow natural history of cervical cancer and the severe but hopefully temporary impact of COVID-19. The commentary introduces the practical validation of some critical components of the strategy, described in three manuscripts detailing recent project results in Asia and Africa. The main phases of a cervical screening program are 1) primary screening of women in the general population, 2) triage testing of the small minority of women that screen positive to determine need for treatment, and 3) treatment of triage-positive women thought to be at highest risk of precancer or even cancer. In each phase, attention must now be paid to safety in relation to SARS-CoV-2 transmission. The new imperatives of the COVID-19 pandemic support self-sampled HPV testing as the primary cervical screening method. Most women can be reassured for several years by a negative test performed on a self-sample collected at home, without need of clinic visit and speculum examination. The advent of relatively inexpensive, rapid and accurate HPV DNA testing makes it possible to return screening results from self-sampling very soon after specimen collection, minimizing loss to follow-up. Partial HPV typing provides important risk stratification useful for triage of HPV-positive women. A second “triage” test is often useful to guide management. In lower-resource settings, visual inspection with acetic acid (VIA) is still proposed but it is inaccurate and poorly reproducible, misclassifying the risk stratification gained by primary HPV testing. A deep-learning based approach to recognizing cervical precancer, adaptable to a smartphone camera, is being validated to improve VIA performance. The advent and approval of thermal ablation permits quick, affordable and safe, immediate treatment at the triage clinic of the majority of HPV-positive, triage-positive women. Conclusions Overall, only a small percentage of women in cervical screening programs need to attend the hospital clinic for a surgical procedure, particularly when screening is targeted to the optimal age range for detection of precancer rather than older ages with decreased visual screening performance and higher risks of hard-to-treat outcomes including invasive cancer.

ObjectiveImplementation of a novel, rapid, high-volume, see-and-treat cervical cancer screening programme using self-swab human papillomavirus (HPV) testing and digital colposcopy in underserved regions of Yunnan China.Design480–980 women per day self-swabbed for high-risk HPV (hrHPV+). Four careHPV machines (Qiagen) were run simultaneously to test the specimens. All hrHPV+ patients were contacted the same day and digital colposcopy was performed with the enhanced visual assessment system (MobileODT). Digital images were obtained, and all suspected lesions were biopsied and then treated.SettingRural and underserved areas of the Yunnan province, Kunming municipality.Participants3600 women, mean age 50.2 years, who had never been screened for cervical cancer. The women were of the Yi, Hui, Dai and Han ethnicities.InterventionsCryotherapy was performed on all lesions suspicious for cervical intraepithelial neoplasia (CIN) 1 and loop electrosurgical excision procedure was performed on all lesions suspicious for ≥CIN2. Endocervical curettage was performed if the transformation zone was not fully visualised.Results216 women (6%) were hrHPV+. 168 underwent same-day colposcopy (23 CIN1, 17≥CIN2). Digital colposcopy was able to identify 15 of 16 (93.8%)≥CIN2 lesions.ConclusionsThis study illustrates a high-volume, rapid and practical strategy that can be used to screen and treat an ethnically diverse group of Chinese women. First, HPV self-sampling allows large numbers of women to be screened rapidly and relatively inexpensively. Only hrHPV+ women will then require further evaluation. Digital colposcopy is then performed on hrHPV+ women with a portable digital colposcope. The high-resolution images obtained can facilitate appropriate same-day treatment as they are able to accurately distinguish between CIN1 and ≥CIN2 lesions.

Introduction: Dyspareunia caused by vulvovaginal atrophy is a primary symptom of genitourinary syndrome of menopause (GSM), a chronic, progressive medical condition that results from estrogen and androgen deficiency at menopause. Dehydroepiandrosterone (DHEA, prasterone) is an endogenous precursor steroid hormone that is metabolized into both androgens and estrogens that has been recently been approved by the FDA for the treatment of moderate to severe dyspareunia caused by vulvovaginal atrophy secondary to menopause.Areas covered: This is a comprehensive drug evaluation describing the chemical composition, pharmacokinetics, metabolism, clinical efficacy and safety of dehydroepiandrosterone (prasterone) in the treatment of dyspareunia and VVA secondary to menopause. Preclinical and clinical data suggesting further potential uses, benefits, and contraindications in the genitourinary health of postmenopausal women are also considered.Expert opinion: Intravaginal dehydroepiandrosterone (prasterone) is effective for the management of dyspareunia secondary to menopause and may be effective in the treatment of other types of sexual dysfunction that are secondary to menopause. Further studies should explore additional dosing regimens and different indications.

Female genital cosmetic surgeries (FGCSs) and procedures are increasingly being advertised as common, simple, and complication-free, capable of not only improving aesthetic appearance but also increasing self-esteem and sexual pleasure.Guidelines for physicians and clear, scientifically correct information for patients must be made available, to minimize the number of ineffective or deleterious procedures.The International Society for the Study of Vulvovaginal Disease positions/recommendations regarding FGCS are as follows:1. There is a wide variation regarding genital normalcy; providers must be able to explain this to women.2. There are no data supporting FGCS including, G-spot augmentation, hymenoplasty, vulvar and perianal bleaching/whitening, vaginal tightening procedures, and other procedures aimed at increasing sexual function.3. Women should not be offered FGCS before the age of 18 years.4. Women undergoing FGCS should be evaluated by a provider with expertise in vulvovaginal diseases, including attention to their psychological, social, and sexual context. Evaluation by an experienced mental health provider should be considered when the motivation for seeking surgery and/or expectations are not clear or realistic.5. Female genital cosmetic surgery is not exempt from complications.6. Informed consent must always be obtained.7. Surgeons performing FGCS should refrain from solicitous advertising or promoting procedures without scientific basis, including on Web sites.8. Surgeons should not perform surgery that they do not agree with and explain their rationale/position when pressured by patients.9. The genital surgeon must be adequately trained in performing FGCS including knowledge of the anatomy, physiology and pathophysiology of the vulva, vagina and adjacent organs.

Three scientific societies, the International Society for the Study of Vulvovaginal Disease (ISSVD), the International Society for the Study of Women Sexual Health (ISSWSH), and the International Pelvic Pain Society (IPPS) developed the "2015 ISSVD, ISSWSH, and IPPS Consensus Terminology and Classification of Persistent Vulvar Pain and Vulvodynia" (referred to as the "2015 consensus terminology").The terminology included 11 descriptors of vulvodynia. However, the definitions of the descriptors were not included in the 2015 consensus terminology publications. The objective of this article was to provide these definitions.The ISSVD led a discussion on the definitions for the 11 vulvodynia descriptors, with participation from the ISSWSH and IPPS. The definitions were created through a consensus process.The definitions are described and the rationale for their choice is elucidated.The definitions of vulvodynia descriptors were determined by a multistaged process of discussion among health care providers with expertise in the pathophysiology, evaluation, and treatment of vulvodynia. The definitions were approved by the ISSVD, ISSWSH, and IPPS. It is recommended that these definitions of vulvodynia descriptors as well as the 2015 consensus terminology be used for the classification of vulvodynia.

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.

Introduction Vulvodynia is defined as vulvar pain of at least 3 months duration without a clear identifiable cause. There are currently no validated questionnaires that assess the experience of women with localized vulvodynia of the vestibule (vestibulodynia, previously known as vulvar vestibulitis) that meet the requirements of the Food and Drug Administration's Patient Reported Outcome (PRO) Guidance. Aim To develop a new content-valid PRO assessment in accordance with the Food and Drug Administration's PRO guidance to assess the symptoms and impacts of localized vulvodynia. Material and Methods Participants were recruited for concept elicitation interviews (ie, interviews with open-ended questions with the goal of eliciting volunteered data about the symptoms and impacts of vulvodynia). Participants were identified as having localized vulvodynia by clinicians who were experts in treating vulvar disorders. Eligibility was confirmed by the recruiting clinician, and informed consent was obtained; participants were then scheduled for in-person interviews. 25 participants were interviewed from United States (US). After concept elicitation interviews, the draft Vulvodynia Experience Questionnaire (VEQ) was developed based on the results. Cognitive interviews were conducted with 20 participants from US sites to assess the content validity of the VEQ (eg, interpretation and clarity of the items, relevance of concepts). The VEQ was further revised after cognitive interviews. All interviews were conducted face-to-face, audio-recorded, transcribed verbatim, anonymized, and analyzed using a qualitative data analysis software program. Results 17 unique symptoms and 32 unique impacts were reported during concept elicitation interviews. Pain (n = 25, 100%) and burning (n = 24, 96%) were the most frequently reported symptoms of localized vulvodynia, and negative impact on emotional well-being (n = 25, 100%) was the most frequently reported impact. After analysis, item generation, and cognitive interviews, the resulting VEQ v2.0 contains 3 parts (part 1, pain; part 2, associated symptoms; part 3, impacts) with a total of 25 items that measure the most frequently reported symptoms and impacts of localized vulvodynia. Strength and Limitations The VEQ is a multidimensional assessment of the core symptoms and impacts of localized vulvodynia that, after additional psychometric testing including the ability to detect change, may be used in clinical trials to characterize the benefits of novel treatments. The VEQ requires additional testing to establish its cultural relevance and linguistic validity in other countries. Conclusion The VEQ is a novel method of collecting information on localized vulvodynia symptoms and impacts that may be suitable for use in clinical trials after psychometric testing.

Background Understanding the molecular alterations associated with breast cancer (BC) progression may lead to more effective strategies for both prevention and management. The current model of BC progression suggests a linear, multistep process from normal epithelial to atypical ductal hyperplasia (ADH), to ductal carcinoma in situ (DCIS), and then invasive ductal carcinoma (IDC). Up to 20% ADH and 40% DCIS lesions progress to invasive BC if left untreated. Deciphering the molecular mechanisms during BC progression is therefore crucial to prevent over- or under-treatment. Our previous work demonstrated that miR-671-5p serves as a tumor suppressor by targeting Forkhead box protein M1 (FOXM1)-mediated epithelial-to-mesenchymal transition (EMT) in BC. Here, we aim to explore the role of miR-671-5p in the progression of BC oncogenic transformation and treatment. Methods The 21T series cell lines, which were originally derived from the same patient with metastatic BC, including normal epithelia (H16N2), ADH (21PT), primary DCIS (21NT), and cells derived from pleural effusion of lung metastasis (21MT), and human BC specimens were used. Microdissection, miRNA transfection, dual-luciferase, radio- and chemosensitivity, and host-cell reactivation (HCR) assays were performed. Results Expression of miR-671-5p displays a gradual dynamic decrease from ADH, to DCIS, and to IDC. Interestingly, the decreased expression of miR-671-5p detected in ADH coexisted with advanced lesions, such as DCIS and/or IDC (cADH), but not in simple ADH (sADH). Ectopic transfection of miR-671-5p significantly inhibited cell proliferation in 21NT (DCIS) and 21MT (IDC), but not in H16N2 (normal) and 21PT (ADH) cell lines. At the same time, the effect exhibited in time- and dose-dependent manner. Interestingly, miR-671-5p significantly suppressed invasion in 21PT, 21NT, and 21MT cell lines. Furthermore, miR-671-5p suppressed FOXM1-mediated EMT in all 21T cell lines. In addition, miR-671-5p sensitizes these cell lines to UV and chemotherapeutic exposure by reducing the DNA repair capability. Conclusions miR-671-5p displays a dynamic decrease expression during the oncogenic transition of BC by suppressing FOXM1-mediated EMT and DNA repair. Therefore, miR-671-5p may serve as a novel biomarker for early BC detection as well as a therapeutic target for BC management. Electronic supplementary material The online version of this article (10.1186/s13058-019-1173-5) contains supplementary material, which is available to authorized users.

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.

Lichen sclerosus (LS) is an inflammatory dermatosis with a predilection for anogenital skin. Developing lesions lead to vulvar pain and sexual dysfunction, with a significant loss of structural anatomical architecture, sclerosis, and increased risk of malignancy. Onset may occur at any age in both sexes, but typically affects more females than males, presenting in a bimodal fashion among pre-pubertal children and middle-aged adults. A definitive cure remains elusive as the exact pathogenesis of LS remains unknown. A general review of LS, histologic challenges, along with amounting support for LS as an autoimmune disease with preference for a Th1 immune response against a genetic background is summarized. In addition to the classically referenced ECM1 (extracellular matrix protein 1), a following discussion of other immune and genetic targets more recently implicated as causative or accelerant agents of disease, particularly miR-155, downstream targets of ECM1, galectin-7, p53, and epigenetic modifications to CDKN2A, are addressed from the viewpoint of their involvement in three different, but interconnected aspects of LS pathology. Collectively, these emerging targets serve not only as inherently potential therapeutic targets for treatment, but may also provide further insight into this debilitating and cryptic disease.

Though a large number of women suffer from vulvar pain and dyspareunia, many clinicians feel that they lack the knowledge to adequately evaluate, diagnose, and treat women with vulvovaginal pain. This review examines the new International Society for the Study of Vulvovaginal Disease (ISSVD)/International Society for the Study of Women’s Sexual Health (ISSWSH)/International Pelvic Pain Society (IPPS) terminology of vulvar pain and vulvodynia, reviews a diagnostic algorithm that can help to differentiate between different types of vulvar pain, and discusses non-medical, medical, and surgical treatment options for provoked vestibulodynia (PVD; vulvodynia confined to the vestibule). The combination of this new terminology, diagnostic algorithm, and potential treatments will allow for more appropriately targeted treatments for women with PVD.

Physicians often feel challenged in the diagnosis and management of vulvar diseases and their effects on psychosexual health. Vulvar dermatoses must be considered in the differential diagnosis of women experiencing female sexual dysfunction or vulvovaginal pain. This review will focus on the diagnosis and treatment of common vulvar dermatoses, including vulvar contact dermatitis, lichen simplex chronicus, vulvar psoriasis, lichen sclerosus, lichen planus, and vulvar intraepithelial neoplasia. The impact of these disorders on sexual well-being will be emphasized. A detailed history and physical examination, backed by confident knowledge of vulvar dermatoses, will aid in diagnosis and management of these diseases. Current gold-standard treatments will be discussed as well as innovative therapeutic approaches currently being developed. With increased clinician awareness and further research, vulvar dermatoses and resulting sexual dysfunction can be appropriately managed.

Introduction Ospemifene (Osphena, Shionogi Inc, Florham, NJ, USA) is an estrogen agonist and antagonist approved by the U.S. Federal Drug Administration for the treatment of “moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause.” Although published, peer-reviewed, placebo-controlled studies have shown objective improvement in dyspareunia and in vaginal atrophy, there are no published data that have assessed changes in vulvar atrophy after the use of ospemifene. Aim To present two cases of women with severe vulvar atrophy that showed no improvement with the use of ospemifene. Methods A review of two recent cases of a clinic specializing in the treatment of vulvovaginal disorders was performed. Case 1 was a 53-year-old menopausal woman who presented with non-provoked vulvar and vaginal discomfort and introital dyspareunia. She had used ospemifene 60 mg/d for 1.5 years without improvement in her symptoms before presentation. Case 2 was a 57-year-old menopausal woman who also presented with non-provoked vulvar rawness, burning, irritation, vaginal dryness, and introital dyspareunia. She had started ospemifene 60 mg/d 1 year before presentation and reported mild improvement in her vaginal dryness but no improvement in her vulvar irritation or introital dyspareunia. Main Outcome Measures Change in vulvar atrophy and introital dyspareunia. Conclusion These cases highlight the need to perform additional clinical trials that specifically assess the efficacy of ospemifene for changes in vulvar atrophy.

Introduction In 2014, the Executive Council of the International Society for the Study of Vulvovaginal Disease (ISSVD), the Boards of Directors of the International Society for the Study of Women's Sexual Health (ISSWSH), and the International Pelvic Pain Society (IPPS) acknowledged the need to revise the current terminology of vulvar pain, based on the significant increase in high quality etiologic studies published in the last decade. Methods The new terminology was achieved in four steps. The first involved a terminology consensus conference with representatives of the three societies, held in April 2015. Then, an analysis of the relevant published studies was used to establish a level of evidence for each factor associated with vulvodynia. The terminology was amended based on feedback from members of the societies. Finally, each society's board accepted the new terminology. Results and Conclusion In 2015, the ISSVD, ISSWSH, and IPPS adopted a new vulvar pain and vulvodynia terminology that acknowledges the complexity of the clinical presentation and pathophysiology involved in vulvar pain and vulvodynia, and incorporates new information derived from evidence-based studies conducted since the last terminology published in 2003.

Introduction Vulvodynia constitutes a highly prevalent form of chronic genital pain in women, and current information regarding its definition, prevalence, impact, and pathophysiologic factors involved is needed. Aim To update the scientific evidence published in 2010 from the Third International Consultation of Sexual Medicine pertaining to the definition, prevalence, impact, and pathophysiologic factors of women's sexual pain. Methods An expert committee, as part of the Fourth International Consultation of Sexual Medicine, comprised of researchers and clinicians from biological and social science disciplines, reviewed the scientific evidence on the definition, prevalence, impact, and pathophysiologic factors related to chronic genital pain. Main Outcome Measures A review of the definition, prevalence, impact, and pathophysiological factors involved in vulvodynia. Results Vulvodynia is a prevalent and highly impactful genital pain condition. Numerous factors have been implicated in its development and maintenance. Conclusion What is becoming increasingly apparent is that it likely represents the end point of different factors that can differ from patient to patient. Longitudinal research is needed to shed light on risk factors involved in the expression of vulvodynia, as well as in potential subgroups of affected patients, in order to develop an empirically supported treatment algorithm.

The objective of this consensus document is to broaden the perspective on clinical management of genitourinary syndrome of menopause to include androgens.A modified Delphi method was used to reach consensus among the 14 international panelists representing multiple disciplines and societies.Menopause-related genitourinary symptoms affect over 50% of midlife and older women. These symptoms have a marked impact on sexual functioning, daily activities, emotional well-being, body image, and interpersonal relations. Tissues in the genitourinary system are both androgen and estrogen-dependent. The clitoris, vestibule, including minor and major vestibular glands, urethra, anterior vaginal wall, periurethral tissue, and pelvic floor are androgen-responsive. Historically, treatment of postmenopausal genitourinary symptoms involved both androgens and estrogens. This subsequently gave rise to predominantly estrogen-based therapies. More recently, double-blind, placebo-controlled clinical trials have demonstrated that local vaginal dehydroepiandrosterone improves symptoms in postmenopausal women, including moderate to severe dyspareunia. Limited data suggest that systemic testosterone treatment may improve vaginal epithelial health and blood flow. Open-label studies that have used high doses of intravaginal testosterone in the presence of aromatase inhibitor therapy for breast cancer have resulted in supraphysiological serum testosterone levels, and have been reported to lower vaginal pH, improve the vaginal maturation index, and reduce dyspareunia.Vaginal dehydroepiandrosterone, hypothesized to enhance local production of both androgen and estrogen, is effective for the management of dyspareunia in menopause. Vaginal testosterone offers potential as a treatment for genitourinary syndrome of menopause, but more studies are needed.

Introduction Lichen sclerosus (LS) is a chronic inflammatory dermatosis, usually affecting the anogenital skin in women. This chronic inflammation can cause scarring of genitalia including narrowing of the introitus and phimosis of the clitoris. These architectural changes can lead to recurrent tearing during intercourse (vulvar granuloma fissuratum) and decreased clitoral sensation. Surgical correction of vulvar granuloma fissuratum (VGF) and clitoral phimosis can be performed, but there is little data on the patient satisfaction and complications following these surgical procedures. Aim To evaluate patient experience and outcomes in women undergoing surgical correction of scarring caused by anogenital LS. Methods A retrospective chart review of patients at a vulvar disorders clinic was performed to identify women who had undergone surgical correction of clitoral phimosis or lysis of vulvar adhesions for VGF due to LS. Twenty-eight women were contacted via telephone between 4 and 130 months postoperatively. An eight-question survey was used to determine patient experience and outcomes. Main Outcome Measures All participants completed an eight-question survey to evaluate patient satisfaction with the surgery, effects on clitoral sensation, orgasm and pain with intercourse, postoperative symptoms or complications, and the presence of recurrent vulvar scarring. Results Participants reported that they were either very satisfied (44%) or satisfied (40%) with the procedure. Of the women who experienced decreased clitoral sensation prior to surgery, 75% endorsed increased clitoral sensitivity postoperatively. Of the women who had dyspareunia prior to surgery, the majority of women reported having pain-free sex (33%) or improved but not completely pain-free sex (58%) after surgery. There were no complications or symptoms made worse by the surgical procedures. Conclusions This study shows high patient satisfaction and low complication risk associated with surgical correction of clitoral phimosis and lysis of vulvar adhesions for VGF caused by LS. Patients reported improvement in clitoral sensation and ability to achieve orgasm, as well as decreased dyspareunia. Surgical correction of vulvar scarring is a viable option to restore vulvar anatomy and sexual function in appropriate candidates with anogenital LS.