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Archives of Gynecology and Obstetrics Sep 2022Despite the vaginal mucosa is able to respond to allergenic stimuli, vaginal allergic responses have been under investigated in clinical practice. Thus, we aimed to... (Review)
Review
PURPOSE
Despite the vaginal mucosa is able to respond to allergenic stimuli, vaginal allergic responses have been under investigated in clinical practice. Thus, we aimed to identify the most frequent etiological agents responsible for vulvovaginal allergies, the prevalent signs/symptoms, and the diagnostic tests applied in this clinical condition.
METHODS
Literature search was performed on PubMed, Scopus, Scielo, Web of Science, and EMBASE. The study protocol was registered on PROSPERO (CRD42020167238). Studies were divided in two groups depending on allergen exposure route. Due to a significant number of studies correlating allergy to Candida infection, subgroup analysis was included.
RESULTS
In direct exposure cases, Human Seminal Plasma was the most prevalent allergen, sensitizing 73% of affected women. These women presented localized swelling and burning as prevalent symptoms, affecting 42/68 and 36/68 women, respectively. Cutaneous Prick tests were applied in 58/68 women, either alone or combined with IgE measurements. Regarding cases of indirect/unidentified exposure, house dust mites was the most prevalent allergen (54%), followed by pollen (44%). Predominant symptoms were vulvar pruritus and burning, affecting 67/98 and 52/98 women. Skin prick test was the most prevalent diagnostic method used among different studies. Hypersensitivity toward Candida antigen was present in only half (163/323) of women presenting concomitant allergy and Candida infection.
CONCLUSION
From the two types of allergen exposure that can cause vulvovaginal allergic responses, direct contact of the antigen with the vulva and/or vagina was the most prevalent. Still, allergens can also sensitize the vaginal mucosa secondarily to other exposure route, specifically aeroallergens.
Topics: Allergens; Candidiasis; Female; Humans; Hypersensitivity; Skin Tests; Vulvovaginitis
PubMed: 34825938
DOI: 10.1007/s00404-021-06332-z -
Imiquimod for Cervical and Vaginal Intraepithelial Neoplasia: A Systematic Review and Meta-analysis.Obstetrics and Gynecology Aug 2023To evaluate the treatment efficacy and the risk of adverse events of imiquimod for cervical intraepithelial neoplasia (CIN) and vaginal intraepithelial neoplasia (VAIN),... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the treatment efficacy and the risk of adverse events of imiquimod for cervical intraepithelial neoplasia (CIN) and vaginal intraepithelial neoplasia (VAIN), compared with placebo or no intervention.
DATA SOURCES
We searched Cochrane, PubMed, ISRCTN registry, ClinicalTrials.gov , and the World Health Organization International Clinical Trials Registry Platform up to November 23, 2022.
METHODS OF STUDY SELECTION
We included randomized controlled trials and prospective nonrandomized studies with control arms that investigated the efficacy of imiquimod for histologically confirmed CIN or VAIN. The primary outcomes were histologic regression of the disease (primary efficacy outcome) and treatment discontinuation due to side effects (primary safety outcome). We estimated pooled odds ratios (ORs) of imiquimod, compared with placebo or no intervention. We also conducted a meta-analysis of the proportions of patients with adverse events in the imiquimod arms.
TABULATION, INTEGRATION, AND RESULTS
Four studies contributed to the pooled OR for the primary efficacy outcome. An additional four studies were available for meta-analyses of proportions in the imiquimod arm. Imiquimod was associated with increased probability of regression (pooled OR 4.05, 95% CI 2.08-7.89). Pooled OR for CIN in the three studies was 4.27 (95% CI 2.11-8.66); results of one study were available for VAIN (OR, 2.67, 95% CI 0.36-19.71). Pooled probability for primary safety outcome in the imiquimod arm was 0.07 (95% CI 0.03-0.14). The pooled probabilities (95% CI) of secondary outcomes were 0.51 (0.20-0.81) for fever, 0.53 (0.31-0.73) for arthralgia or myalgia, 0.31 (0.18-0.47) for abdominal pain, 0.28 (0.09-0.61) for abnormal vaginal discharge or genital bleeding, 0.48 (0.16-0.82) for vulvovaginal pain, and 0.02 (0.01-0.06) for vaginal ulceration.
CONCLUSION
Imiquimod was found to be effective for CIN, whereas data on VAIN were limited. Although local and systemic complications are common, treatment discontinuation is infrequent. Thus, imiquimod is potentially an alternative therapy to surgery for CIN.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, CRD42022377982.
Topics: Female; Humans; Imiquimod; Antineoplastic Agents; Prospective Studies; Aminoquinolines; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms
PubMed: 37411024
DOI: 10.1097/AOG.0000000000005256 -
BMC Women's Health Mar 2023Vulvovaginal yeast infections in pregnancy are common and can cause extensive inflammation, which could contribute to adverse pregnancy outcomes. Symptomatic yeast... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vulvovaginal yeast infections in pregnancy are common and can cause extensive inflammation, which could contribute to adverse pregnancy outcomes. Symptomatic yeast infections are likely to cause more inflammation than asymptomatic. The objective of this study was to investigate associations between symptomatic and asymptomatic vulvovaginal yeast infections in pregnancy and perinatal outcomes.
METHODS
We did a systematic review and searched eight databases until 01 July 2022. We included studies reporting on pregnant women with and without laboratory confirmed vulvovaginal yeast infection and preterm birth or eight other perinatal outcomes. We used random effects meta-analysis to calculate summary odds ratios (OR), 95% confidence intervals (CI) and prediction intervals for the association between yeast infection and outcomes. We described findings from studies with multivariable analyses. We assessed the risk of bias using published tools.
RESULTS
We screened 3909 references and included 57 studies. Only 22/57 studies reported information about participant vulvovaginal symptoms. Preterm birth was an outcome in 35/57 studies (49,161 women). In 32/35 studies with available data, the summary OR from univariable analyses was 1.01 (95% CI 0.84-1.21, I 60%, prediction interval 0.45-2.23). In analyses stratified by symptom status, we found ORs of 1.44 (95% CI 0.92-2.26) in two studies with ≥ 50% symptomatic participants, 0.84 (95% CI 0.45-1.58) in seven studies with < 50% symptomatic participants, and 1.12 (95% CI 0.94-1.35) in four studies with asymptomatic participants. In three studies with multivariable analysis, adjusted ORs were greater than one but CIs were compatible with there being no association. We did not find associations between vulvovaginal yeast infection and any secondary outcome. Most studies were at high risk of bias in at least one domain and only three studies controlled for confounding.
CONCLUSIONS
We did not find strong statistical evidence of an increased risk for preterm birth or eight other adverse perinatal outcomes, in pregnant women with either symptomatic or asymptomatic vulvovaginal yeast infection. The available evidence is insufficient to make recommendations about testing and treatment of vulvovaginal yeast infection in pregnancy. Future studies should assess vulvovaginal symptoms, yeast organism loads, concomitant vaginal or cervical infections, and microbiota using state-of-the-art diagnostics.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42020197564.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Premature Birth; Saccharomyces cerevisiae; Pregnancy Outcome; Vagina; Inflammation
PubMed: 36944953
DOI: 10.1186/s12905-023-02258-7 -
Menopause (New York, N.Y.) Aug 2023Ospemifene is a novel selective estrogen receptor modulator developed for the treatment of moderate to severe postmenopausal vulvovaginal atrophy (VVA). (Meta-Analysis)
Meta-Analysis
Efficacy, tolerability, and endometrial safety of ospemifene compared with current therapies for the treatment of vulvovaginal atrophy: a systematic literature review and network meta-analysis.
IMPORTANCE
Ospemifene is a novel selective estrogen receptor modulator developed for the treatment of moderate to severe postmenopausal vulvovaginal atrophy (VVA).
OBJECTIVE
The aim of the study is to perform a systematic literature review (SLR) and network meta-analysis (NMA) to assess the efficacy and safety of ospemifene compared with other therapies used in the treatment of VVA in North America and Europe.
EVIDENCE REVIEW
Electronic database searches were conducted in November 2021 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized or nonrandomized controlled trials targeting postmenopausal women with moderate to severe dyspareunia and/or vaginal dryness and involving ospemifene or at least one VVA local treatment were considered. Efficacy data included changes from baseline in superficial and parabasal cells, vaginal pH, and the most bothersome symptom of vaginal dryness or dyspareunia, as required for regulatory approval. Endometrial outcomes were endometrial thickness and histologic classifications, including endometrial polyp, hyperplasia, and cancer. For efficacy and safety outcomes, a Bayesian NMA was performed. Endometrial outcomes were compared in descriptive analyses.
FINDINGS
A total of 44 controlled trials met the eligibility criteria ( N = 12,637 participants). Network meta-analysis results showed that ospemifene was not statistically different from other active therapies in most efficacy and safety results. For all treatments, including ospemifene, the posttreatment endometrial thickness values (up to 52 wk of treatment) were under the recognized clinical threshold value of 4 mm for significant risk of endometrial pathology. Specifically, for women treated with ospemifene, endometrial thickness ranged between 2.1 and 2.3 mm at baseline and 2.5 and 3.2 mm after treatment. No cases of endometrial carcinoma or hyperplasia were observed in ospemifene trials, nor polyps with atypical hyperplasia or cancer after up to 52 weeks of treatment.
CONCLUSIONS AND RELEVANCE
Ospemifene is an efficacious, well-tolerated, and safe therapeutic option for postmenopausal women with moderate to severe symptoms of VVA. Efficacy and safety outcomes with ospemifene are similar to other VVA therapies in North America and Europe.
Topics: Female; Humans; Dyspareunia; Vagina; Hyperplasia; Bayes Theorem; Network Meta-Analysis; Vulva; Atrophy; Tamoxifen; Selective Estrogen Receptor Modulators; Vaginal Diseases; Endometrial Neoplasms
PubMed: 37369079
DOI: 10.1097/GME.0000000000002211 -
The Cochrane Database of Systematic... Nov 2017Vulvovaginal candidiasis (VVC) is estimated to be the second most common form of infection after bacterial vaginosis. The ability of probiotics in maintaining and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vulvovaginal candidiasis (VVC) is estimated to be the second most common form of infection after bacterial vaginosis. The ability of probiotics in maintaining and recovering the normal vaginal microbiota, and their potential ability to resist Candidas give rise to the concept of using probiotics for the treatment of VVC.
OBJECTIVES
To assess the effectiveness and safety of probiotics for the treatment of vulvovaginal candidiasis in non-pregnant women.
SEARCH METHODS
We searched the following databases to October 2017: Sexually Transmitted Infections Cochrane Review Group's Specialized Register, CENTRAL, MEDLINE, Embase and eight other databases. We searched in following international resources: World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, Web of Science and OpenGrey. We checked specialty journals, reference lists of published articles and conference proceedings. We collected information from pharmaceutical companies and experts in the field.
SELECTION CRITERIA
Randomized controlled trials (RCT) using probiotics, alone or as adjuvants to conventional antifungal drugs, to treat VVC in non-pregnant women. Trials recruiting women with recurrent VVC, coinfection with other vulvovaginal infections, diabetes mellitus, immunosuppressive disorders or taking immunosuppressant medication were ineligible for inclusion. Probiotics were included if they were made from single or multiple species and in any preparation type/dosage/route of administration.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for eligibility and quality and extracted data. We resolved any disagreements through consensus. The quality of the evidence was assessed using the GRADE approach.
MAIN RESULTS
Ten RCTs (1656 participants) met our inclusion criteria, and pharmaceutical industry funded none of these trials. All trials used probiotics as adjuvant therapy to antifungal drugs. Probiotics increased the rate of short-term clinical cure (risk ratio (RR) 1.14, 95% confidence interval (CI) 1.05 to 1.24, 695 participants, 5 studies, low quality evidence) and mycological cure (RR 1.06, 95% CI 1.02 to 1.10, 969 participants, 7 studies, low quality evidence) and decreased relapse rate at one month (RR 0.34, 95% CI 0.17 to 0.68, 388 participants, 3 studies, very low quality evidence). However, this effect did not translate into a higher frequency of long-term clinical cure (one month after treatment: RR 1.07, 95% CI 0.86 to 1.33, 172 participants, 1 study, very low quality evidence; three months after treatment: RR 1.30, 95% CI 1.00 to 1.70, 172 participants, one study, very low quality evidence) or mycological cure (one month after treatment: RR 1.26, 95% CI 0.93 to 1.71, 627 participants, 3 studies, very low quality evidence; three months after treatment: RR 1.16, 95% CI 1.00 to 1.35, 172 participants, one study, very low quality evidence). Probiotics use did not increase the frequency of serious (RR 0.80, 95% CI 0.22 to 2.94; 440 participants, 2 studies, low quality evidence). We found no eligible RCTs for outcomes as time to first relapse, need for additional treatment at the end of therapy, patient satisfaction and cost effectiveness.
AUTHORS' CONCLUSIONS
Low and very low quality evidence shows that, compared with conventional treatment, the use of probiotics as an adjuvant therapy could increases the rate of short-term clinical and mycological cure and decrease the relapse rate at one month but this did not translate into a higher frequency of long-term clinical or mycological cure. Probiotics use does not seem to increase the frequency of serious or non-serious adverse events. There is a need for well-designed RCTs with standardized methodologies, longer follow-up and larger sample size.
Topics: Administration, Intravaginal; Antifungal Agents; Candidiasis, Vulvovaginal; Clotrimazole; Female; Fluconazole; Humans; Imidazoles; Miconazole; Probiotics; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention
PubMed: 29168557
DOI: 10.1002/14651858.CD010496.pub2 -
Clinical Breast Cancer Dec 2023Vulvo-vaginal atrophy (VVA) or genitourinary syndrome of menopause (GSM) is a common condition among breast cancer (BC) patients, especially those undergoing... (Meta-Analysis)
Meta-Analysis Review
Vulvo-vaginal atrophy (VVA) or genitourinary syndrome of menopause (GSM) is a common condition among breast cancer (BC) patients, especially those undergoing antiestrogen therapy. Despite being an option in refractory cases, the safety of hormonal treatment remains uncertain in this population. The aim of this study was to review the safety and serum estrogen levels of hormonal therapy in patients with BC history presenting with VVA symptoms. Pubmed, Embase, and Cochrane were searched for studies comparing different hormonal treatment options for VVA in breast cancer survivors. Statistical analysis was performed using a random effects model and heterogeneity using Cochran's Q-statistic and the I2 index. We included 17 studies, of which 5 were randomized controlled trials (RCTs). Treatment modalities included in this study were topical vaginal estradiol and estriol preparations, vaginally applied testosterone, DHEA, and ospemifene. We found that, among patients treated with the estriol and estradiol preparations, there was an average increase of 7.67 pg/mL (SMD 7.67 pg/mL; 95% CI -1.00, 16.35; p < .001). Analysis of the testosterone group found temporary peaks of serum estradiol levels, but 1 study showed persistent elevation above normal postmenopausal levels. One study with prasterone revealed no elevation of serum estradiol concentration. One study with ospemifene demonstrated no increase in the risk of BC recurrence. In conclusion, among treatments available for BC survivors, low-dose vaginal estrogen showed the smallest changes in serum estradiol levels and had the most evidence, but safety remains unclear, especially for patients on aromatase inhibitors. Alternative treatments such as ospemifene need more data supporting safety and efficacy. These results suggest that concerns related to cancer recurrence should keep aiming for the lowest possible concentration.
Topics: Female; Humans; Breast Neoplasms; Cancer Survivors; Neoplasm Recurrence, Local; Vaginal Diseases; Vagina; Estradiol; Survivors; Testosterone; Estrogens; Atrophy; Estriol
PubMed: 37806915
DOI: 10.1016/j.clbc.2023.08.003 -
Journal of Lower Genital Tract Disease Oct 2021This systematic review aimed to present the available literature on plasma cell vulvitis (PCV), a relatively uncommon form of inflammatory vulvovaginal dermatitis.
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.
Topics: Adolescent; Adult; Aged; Child; Female; Humans; Imiquimod; Middle Aged; Observational Studies as Topic; Plasma Cells; Vulvitis; Young Adult
PubMed: 34224535
DOI: 10.1097/LGT.0000000000000617 -
Frontiers in Surgery 2021To describe the available knowledge on vulvo-perineal endometriosis including its diagnosis, clinical management and recurrence rate. We followed the PRISMA guidelines...
To describe the available knowledge on vulvo-perineal endometriosis including its diagnosis, clinical management and recurrence rate. We followed the PRISMA guidelines for Systematic Reviews and our study was prospectively registered with PROSPERO (CRD42020202441). The terms " and " or " were used as keywords. Cochrane Library, Medline/Pubmed, Embase and Clinicaltrials.gov were searched. Papers in English, Spanish, Portuguese, French or Italian from inception to July 30, 2020 were considered. Reference lists of included articles and other literature source such as Google Scholar were also manually scrutinized in order to identify other relevant studies. Two independent reviewers screened potentially eligible studies according to inclusion criteria. Out of 539 reports, 90 studies were eligible including a total of 283 patients. Their mean age was 32.7 ± 7.6 years. Two hundred sixty-three (95.3%) presenting with vulvo-perineal endometriosis have undergone either episiotomy, perineal trauma or vaginal injury or surgery. Only 13 patients (4.7%) developed vulvo-vaginal endometriosis spontaneously i.e., without any apparent condition favoring it. The reasons that motivated the patients to take medical advice were vulvo-perineal cyclical pain increasing during menstruations (98.2% of the patients, = 278). Out of the 281 patients for whom a clinical examination was described, 274 patients (97.5%) showed a vulvo-perineal nodule, mass or swelling while six presented with bluish cutaneous lesions (2.1%) and 1 with bilateral polyps of the labia minora (0.4%). All but one patients underwent surgical excision of their lesions but only 88 patients (28.1%) received additional hormonal therapy. The recurrence rate was 10.2% (29 patients) considering a median follow-up period of 10 months (based on 61 studies). In conclusion, vulvo-perineal endometriosis is a rare entity with approximately 300 cases reported in the literature since 1923. With the available knowledge shown in this systematic review, we encourage all practitioners to think about perineal endometriosis in case of perineal cyclical pain with or without previous perineal damage. Diagnosis should be done with clinical exam, perineal ultrasound and pelvic MRI when available. In case of anal sphincter involvement, perianal ultrasound should be performed. Surgical excision of the lesion should be realized in order to remove the lesion and to confirm the diagnosis histologically. Hormonal treatment could be proposed to attempt to decrease the size of a large lesion before surgery or to avoid recurrence of the lesion. As evidence-based approach to the diagnosis, treatment and recurrence rate of affected patients remains a challenge given its low prevalence, the variations in management found in the articles included and the limited quality of available studies, we suggest that a prospective database on vulvo-perineal endometriosis should be generated to increase knowledge but also awareness among healthcare professionals and optimize patients' care. https://www.crd.york.ac.uk/prospero/, identifier: CRD42020202441.
PubMed: 34046423
DOI: 10.3389/fsurg.2021.637180 -
Medical Mycology Oct 2021Vulvovaginal candidiasis (CVV) is a condition in which signs and symptoms are related to inflammation caused by Candida spp infection. It is the second leading cause of... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Vulvovaginal candidiasis (CVV) is a condition in which signs and symptoms are related to inflammation caused by Candida spp infection. It is the second leading cause of vaginitis in the world, representing a public health problem. The present systematic review comes with the proposal of analyze and identify the available evidence on CVV prevalence in Brazil, pointing out its variability by regions. For this, a systematic literature review was carried out with meta-analysis of cross-sectional and cohort studies, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guide recommendations, and was registered in the International Prospective Register of Systematic Reviews (PROSPERO 2020 CRD42020181695). The databases used for survey were LILACS, Scielo, Scopus, PUBMED, Web of Science and CINAHL. Fifteen studies were selected to estimate CVV prevalence in the Brazilian territory. South and Southeast regions have higher prevalences than the North and Northeast regions, no data were found for the Midwest region. The estimated prevalence for Brazil is 18%, however, it is suggested that this number is higher due to underreporting and the presence of asymptomatic cases. Therefore, new epidemiological studies are recommended throughout Brazil, to elucidate the profile of this disease in the country, in addition to assisting in the elaboration of an appropriate prevention plan by state.
LAY SUMMARY
Data found in the literature regarding the epidemiological profile of vulvovaginal candidiasis in Brazil are obsolete and incomplete, so the present systematic review has the proposal to analyze and identify the evidence on vulvovaginal candidiasis prevalence in Brazil. The estimated prevalence is 18%; however, this number can be higher.
Topics: Animals; Brazil; Candidiasis; Candidiasis, Vulvovaginal; Cross-Sectional Studies; Female; Prevalence
PubMed: 34137857
DOI: 10.1093/mmy/myab034 -
Reproductive Toxicology (Elmsford, N.Y.) Apr 2015Vulvovaginal candidiasis (VVC) affects up to 75% of women at least once during their lifetime, mostly during the reproductive age, and recurrence rate is about 50%.... (Meta-Analysis)
Meta-Analysis Review
Vulvovaginal candidiasis (VVC) affects up to 75% of women at least once during their lifetime, mostly during the reproductive age, and recurrence rate is about 50%. Because half of all pregnancies are unplanned and pregnant women have an increased risk of VVC recurrence, the likelihood of inadvertently being exposed to fluconazole in pregnancy is increased. Thus, we aimed to examine the risk of congenital malformations in the offspring of women exposed to fluconazole in the first trimester of pregnancy. The rate for overall malformations was 1.10 (95% CI 0.98-1.25), for heart defect was 1.29 (95% CI 1.05-1.58), for craniofacial defects was 1.25 (95% CI 0.88-1.77), and for limb/musculoskeletal defects was 0.82 (95% CI 0.59-1.13). In conclusion, the use of fluconazole in the first trimester does not appear to increase the overall risk for congennital malformations. More studies are needed to address the potential increased rate of heart defects.
Topics: Abnormalities, Drug-Induced; Antifungal Agents; Candidiasis, Vulvovaginal; Craniofacial Abnormalities; Female; Fluconazole; Heart Defects, Congenital; Humans; MEDLINE; Pregnancy; Pregnancy Trimester, First
PubMed: 25724389
DOI: 10.1016/j.reprotox.2015.02.009