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MSystems Mar 2024Although vaginitis is closely related to vaginal microecology in females, the precise composition and functional potential of different types of vaginitis remain...
UNLABELLED
Although vaginitis is closely related to vaginal microecology in females, the precise composition and functional potential of different types of vaginitis remain unclear. Here, metagenomic sequencing was applied to analyze the vaginal flora in patients with various forms of vaginitis, including cases with a clue cell proportion ranging from 1% to 20% (Clue1_20), bacterial vaginitis (BV), vulvovaginal candidiasis (VVC), and BV combined with VVC (VVC_BV). Our results identified as an important biomarker between BV and Clue1_20. Moreover, a gradual decrease was observed in the relative abundance of shikimic acid metabolism associated with bacteria producing indole as well as a decline in the abundance of in patients with BV, Clue1_20, and healthy women. Interestingly, the vaginal flora of patients in the VVC_BV group exhibited structural similarities to that of the VVC group, and its potentially functional characteristics resembled those of the BV and VVC groups. Finally, was found in high abundance in healthy samples, greatly contributing to the stability of the vaginal environment. For the further study of , we isolated five strains of from healthy samples and evaluated their capacity to inhibit biofilms and produce lactic acid to select the potential probiotic candidate for improving vaginitis in future clinical studies. Overall, we successfully identified bacterial biomarkers of different vaginitis and characterized the dynamic shifts in vaginal flora between patients with BV and healthy females. This research advances our understanding and holds great promise in enhancing clinical approaches for the treatment of vaginitis.
IMPORTANCE
Vaginitis is one of the most common gynecological diseases, mostly caused by infections of pathogens such as and . In recent years, it has been found that the stability of the vaginal flora plays an important role in vaginitis. Furthermore, the abundant -producing rich lactic acid in the vagina provides a healthy acidic environment such as . The metabolites of can inhibit the colonization of pathogens. Here, we collected the vaginal samples of patients with bacterial vaginitis (BV), vulvovaginal candidiasis (VVC), and BV combined with VVC to discover the differences and relationships among the different kinds of vaginitis by metagenomic sequencing. Furthermore, because of the importance of in promoting vaginal health, we isolated multiple strains from vaginal samples of healthy females and chose the most promising strain with potential probiotic benefits to provide clinical implications for treatment strategies.
Topics: Humans; Female; Vaginosis, Bacterial; Candidiasis, Vulvovaginal; Vagina; Gardnerella vaginalis; Lactobacillus; Lactobacillus crispatus; Lactic Acid
PubMed: 38364107
DOI: 10.1128/msystems.01377-23 -
Menopause (New York, N.Y.) Nov 2023To describe vaginal microbiota classified by community state types (CST) in a diverse cohort of postmenopausal women and evaluate relationships among genitourinary...
OBJECTIVE
To describe vaginal microbiota classified by community state types (CST) in a diverse cohort of postmenopausal women and evaluate relationships among genitourinary syndrome of menopause (GSM) symptoms (vaginal dryness, vulvovaginal irritation, sexual pain, dysuria, urinary urgency), CSTs, estrogen, vaginal maturation index (VMI), and vaginal pH.
METHODS
In the Study of Women's Health Across the Nation, 1,320 women aged 60.4 to 72.5 years self-collected (2015-2017) vaginal samples analyzed for microbiota composition and structure (CSTs) using 16S rRNA gene amplicon sequencing, VMI, and pH. GSM symptoms were collected with self-administered questionnaires; interviewers elicited estrogen use and measured body mass index. Serum E2 and E1 were measured using high-performance liquid chromatography. We analyzed data using Pearson χ2 tests, analysis of variance, Kruskal-Wallis tests, and binomial logistic regression.
RESULTS
The most frequently occurring CST was low Lactobacillus species IV-C (49.8%); 36.4% of women had CSTs dominated by Lactobacillus species. More than half of the women with vaginal atrophy biomarkers (VMI <50 and pH >5) had CST IV-C0, whereas women using estrogen or with higher E1 and E2 levels had a higher prevalence of Lactobacillus crispatus -dominated CST I ( P values < 0.001). Sexual pain was associated with atrophy biomarkers and independently associated with Streptococcus species-dominated CST IV-C1 (odds ratio, 2.26; 95% confidence intervals, 1.20-4.23). For all other GSM symptoms, we found no consistent associations with E1 or E2 levels, atrophy biomarkers, or any CST.
CONCLUSIONS
Although close relationships exist among estrogen, CSTs, VMI, and pH, sexual pain was the only GSM symptom associated with the structure of vaginal microbiota and atrophy biomarkers.
Topics: Female; Humans; Postmenopause; RNA, Ribosomal, 16S; Women's Health; Vagina; Vaginal Diseases; Estrogens; Microbiota; Atrophy; Biomarkers; Pain; Menopause
PubMed: 37788422
DOI: 10.1097/GME.0000000000002263 -
Journal of Ethnopharmacology Jan 2024Longdan Xiegan decoction (LXD) is a standardized herbal prescription originally documented in the "Medical Formula Collection" by the eminent physician Wang Ang during...
ETHNOPHARMACOLOGICAL RELEVANCE
Longdan Xiegan decoction (LXD) is a standardized herbal prescription originally documented in the "Medical Formula Collection" by the eminent physician Wang Ang during the Qing dynasty. It has been used extensively to treat vulvovaginal candidiasis (VVC). However, despite its effectiveness, the mechanism of action remains unknown.
AIM OF THE STUDY
To elucidate the mechanism by which LXD relieves VVC via the Toll-like receptor/MyD88 pathway and activation of the NLRP3 inflammasome.
MATERIALS AND METHODS
Female Kunming mice (n = 96) were randomly divided into six groups: control, VVC model, LXD (10/20/40 mL/kg), and positive drug fluconazole. Mice were vaginally administered Candida albicans (C. albicans) solution (20 μL; 1 × 10 colony-forming units/mL), suspended for 5 min, and observed daily for changes in their condition. Continuous dilution was used to determine the number of colony-forming units. Gram, periodic acid-Schiff, Papanicolaou, and hematoxylin and eosin staining were used to determine the extent of infection. Enzyme-linked immunosorbent assay(ELISA) was used to determine the levels of proinflammatory cytokines IL-1β and IL-18. TLR2, TLR4, MyD88, NF-κB, NLRP3, ASC, and caspase-1 protein expression were determined using western blotting.
RESULTS
C. albicans infection destroyed the integrity of the vaginal mucosa, increased fungal burden and the influx of neutrophils into the vaginal cavity, and promoted the secretion of proinflammatory cytokines. C. albicans stimulated the expression of TLR2, TLR4, MyD88, NF-κB, NLRP3, ASC, and caspase-1 in vaginal tissue. Fungal burden, hyphal formation, and C. albicans adhesion were reduced in the 20 and 40 mL/kg LXD groups. Hematoxylin and eosin staining showed that inflammation was reduced and the stratum corneum had recovered in the 20 and 40 mL/kg LXD groups. LXD (20 and 40 mL/kg) significantly reduced IL-1β, IL-18 levels and the number of neutrophils in vaginal lavage and decreased TLR2, TLR4, MyD88, NF-κB, NLRP3, ASC, and caspase-1 expression.
CONCLUSIONS
This study systematically demonstrated the therapeutic effect of LXD on protein expression and pathological conditions in VVC mice. The results showed that LXD could eliminate the invasion of vaginal hyphae in mice, reduce the recruitment of neutrophils, and reduce the expression of TLR/MyD88 pathway-related proteins and NLRP3 inflammasome. The above results clearly indicate that LXD may profoundly regulate NLRP3 inflammasome through the TLR/MyD88 pathway and play a therapeutic role in VVC.
Topics: Mice; Humans; Female; Animals; Candidiasis, Vulvovaginal; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Myeloid Differentiation Factor 88; Interleukin-18; NF-kappa B; Toll-Like Receptor 2; Toll-Like Receptor 4; Eosine Yellowish-(YS); Hematoxylin; Candida albicans; Cytokines; Caspases
PubMed: 37390876
DOI: 10.1016/j.jep.2023.116869 -
The Annals of Pharmacotherapy Jun 2024The objective of the study is to describe and analyze the pharmacodynamics and pharmacokinetics of oteseconazole as well as the clinical evidence supporting the efficacy... (Review)
Review
OBJECTIVE
The objective of the study is to describe and analyze the pharmacodynamics and pharmacokinetics of oteseconazole as well as the clinical evidence supporting the efficacy of oteseconazole in treating recurrent vulvovaginal candidiasis (RVVC).
DATA SOURCES
A literature search was conducted using MEDLINE and EMBASE databases (2015-June 2023). Search terms included "oteseconazole" OR "VT-1161" or "VIVJOA" AND "RVVC" or "recurrent vulvovaginal candidiasis" or "vulvovaginal candidiasis." Conference abstracts, bibliographies, clinical trials, and drug monographs were included for review.
STUDY SELECTION AND DATA EXTRACTION
Relevant studies in English and clinical trials conducted in humans were reviewed.
DATA SYNTHESIS
Oteseconazole is approved for the treatment of RVVC. In 2 identical phase III studies, oteseconazole was superior to placebo through 48 weeks for preventing recurrence of RVVC (6.7% vs 42.8%, < 0.001 and 3.9% vs 39.4%, < 0.001). In the only phase III trial comparing oteseconazole against active drug, oteseconazole was well tolerated and exhibited noninferiority to fluconazole in acute treatment and superiority to placebo for prevention maintenance through 50 weeks (5.1% vs 42.2%, < 0.001).
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING AGENTS
This review describes the use of oteseconazole for the treatment of RVVC as compared with fluconazole. Oteseconazole is an effective treatment option for common pathogens causing vulvovaginal candidiasis, including and fluconazole-resistant .
CONCLUSIONS
Oteseconazole is an effective and safe treatment option for the management of RVVC though current research lacks comparison with established maintenance regimens. Additional research is needed to ascertain the placement of oteseconazole in the treatment of RVVC.
Topics: Humans; Candidiasis, Vulvovaginal; Female; Antifungal Agents; Recurrence
PubMed: 37650387
DOI: 10.1177/10600280231195649 -
American Journal of Obstetrics and... Sep 2023Postmenopausal vaginal symptoms affect over 60% of women and may substantially impact a woman's quality of life. Since 2012, fractional CO laser has been suggested as a... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Postmenopausal vaginal symptoms affect over 60% of women and may substantially impact a woman's quality of life. Since 2012, fractional CO laser has been suggested as a treatment for this indication. Structural assessment of vaginal epithelium using microscopic biopsy examination has been used as a primary outcome measure and surrogate determinant of success of vaginal laser in previous clinical studies.
OBJECTIVE
This study aimed to report the effects of laser compared with sham treatment on human vaginal epithelium from postmenopausal women using microscopic examination of tissue biopsies.
STUDY DESIGN
This single-center double-blind, sham-controlled randomized controlled trial was performed in a tertiary hospital in Sydney, Australia. A total of 49 postmenopausal women who were symptomatic of at least 1 vaginal symptom (vaginal dryness, burning, itching; dyspareunia; or dryness) were randomized to either laser or sham treatment. For this nested histologic study, participants had a pre- and post-treatment vaginal wall biopsy collected. Biopsy samples were analyzed by 3 independent specialist gynecologic pathologists and categorized as Type 1 (well-estrogenized), 2 (poorly estrogenized), or 3 (combination) mucosae. Other outcomes assessed included symptom severity (visual analog scale for symptoms including most bothersome symptom, and Vulvovaginal Symptom Questionnaire) and Vaginal Health Index. Prespecified secondary analyses of data were performed. Categorical data were analyzed using the Pearson chi-square test (or Fisher exact test if <5 in any category) or related-samples McNemar test for paired nonparametric data. Nonparametric, continuous variables were assessed using Wilcoxon signed-rank test or Mann-Whitney U test, and parametric variables with t test or 1-way analysis of variance as appropriate. All analyses were performed using SPSS software version 26.0 (IBM Corp, Armonk, NY).
RESULTS
There was no significant difference in microscopic features of vaginal epithelium following laser or sham treatment (P=.20). Further subgroup analyses of age, menopause type, duration of reproductive life, time since menopause and BMI, still demonstrated no significant difference between laser and sham groups in histological category of vaginal epithelium. Microscopic features at pre-treatment vaginal biopsy were Type 1 in 27% (13/49). There was no significant difference in VAS score for overall vaginal symptom between those classified as Type 1 vs. Type 2/3 (VAS score overall: Type 1 vs. Type 2/3, (48.1 [95% CI 27.0, 69.2] vs. 61.5 [95% CI 49.8, 73.3]; P=.166).
CONCLUSION
Data from this double-blind, sham-controlled randomized controlled trial demonstrate that fractional CO laser and sham treatment have a comparable histologic effect on vaginal tissue that is not significantly different. Fractional CO laser is not significantly different from sham treatment and should not be recommended for clinical use for postmenopausal vaginal symptoms.
Topics: Female; Humans; Postmenopause; Carbon Dioxide; Quality of Life; Vagina; Vaginal Diseases; Lasers, Gas; Treatment Outcome
PubMed: 37192705
DOI: 10.1016/j.ajog.2023.05.005 -
Climacteric : the Journal of the... Oct 2023This study aimed to evaluate the self-reported satisfaction of Spanish postmenopausal women currently treated for vulvovaginal atrophy (VVA) symptoms.
OBJECTIVE
This study aimed to evaluate the self-reported satisfaction of Spanish postmenopausal women currently treated for vulvovaginal atrophy (VVA) symptoms.
METHODS
The CRETA (CRoss sectional European sTudy on Adherence) is a multicenter cross-sectional study conducted in 29 public and private hospitals in Spain, which enrolled postmenopausal women receiving treatment with ospemifene, local hormone therapy (HT) or vaginal moisturizers for VVA. After the prior informed consent of the patients, sociodemographic and treatment perception data were collected using a structured questionnaire.
RESULTS
Among 752 women who completed the survey, the satisfaction score was significantly higher for the group treated with ospemifene (mean 8.3 ± 1.4) compared with the local HT group (7.2 ± 1.7) and the vaginal moisturizer group (6.5 ± 2.1) according to a 10-point Likert scale ( < 0.0001). Compared to vaginal moisturizers and local HT, participants treated with ospemifene reported the highest adherence (96.7% vs. 70.2% and 78.6%, respectively) and the lowest number of missed doses in the last month (0.6 ± 1.3 standard deviation [SD] vs. 3.5 ± 4.3 SD and 2.0 ± 2.8 SD, respectively) ( < 0.0001). Ospemifene was significantly perceived as easy to use (83.9% vs. 44.9% and 58.6%, respectively; < 0.0001), efficacious in reducing the time to relieve symptoms (17.1% vs. 7.0% and 6.7%, = 0.0005 and = 0.0006, respectively) and convenient for sexual life (53.1% vs. 25.6% and 42.3%, < 0.0001 and = 0.0234, respectively).
CONCLUSIONS
Among postmenopausal women with VVA, treatment with ospemifene has the most positive perceptions and the highest overall satisfaction level and could be an optimal therapeutic approach, maximizing patient adherence.
Topics: Female; Humans; Vagina; Cross-Sectional Studies; Dyspareunia; Tamoxifen; Hormones; Medication Adherence; Atrophy; Personal Satisfaction; Vulva; Vaginal Diseases
PubMed: 37017707
DOI: 10.1080/13697137.2023.2190508 -
Bulletin Du Cancer Sep 2023Anticancer treatments induce vulvovaginal complications that alter the quality of life and sexuality of patients. New technologies, such as photobiomodulation, could...
Anticancer treatments induce vulvovaginal complications that alter the quality of life and sexuality of patients. New technologies, such as photobiomodulation, could address this problem, for which few effective therapeutic solutions exist. The objective of this study was to describe the characteristics of patients seeking treatment and to observe the effects of photobiomodulation. This is a prospective cohort of patients treated for cancer, in failure of first-line medical treatment, managed at the University Hospital of Nîmes. The history, symptoms and impact of the disorders on their quality of life were collected. At follow-up, improvement was assessed using the PGI-I and FSFI questionnaires. Twenty-eight patients were treated. They were all menopausal, half of them after anticancer treatments [chemotherapy (78%), radiotherapy (36%), hormone therapy (36%)]. The main symptom reported was vaginal dryness (72%). Seventy-one percent of patients (n=20) felt that their daily life was affected≥8/10. All patients had sexual dysfunction. Twenty-two patients received at least 6 sessions of photobiomodulation. Seventy-two percent (n=18) of patients felt better or much better after treatment (PGI-I≤2). The median improvement estimated by the patients was 65% (Q1=50%; Q3=72.5%). There was also a significant clinical improvement. No serious adverse events were reported. Due to the small number of patients in a heterogeneous population with no control group, we cannot extrapolate our results. However, the objective was to assess the status of these pathologies and the contribution of photobiomodulation in patients who have failed first-line treatment; and these results are encouraging.
Topics: Female; Humans; Vagina; Quality of Life; Prospective Studies; Vaginal Diseases; Menopause
PubMed: 37183056
DOI: 10.1016/j.bulcan.2023.03.018 -
Journal of Fungi (Basel, Switzerland) Dec 2023The aim of this study is to establish a loop-mediated isothermal amplification (LAMP) method for the rapid detection of vulvovaginal candidiasis (VVC).
PURPOSE
The aim of this study is to establish a loop-mediated isothermal amplification (LAMP) method for the rapid detection of vulvovaginal candidiasis (VVC).
METHODS
We developed and validated a loop-mediated isothermal amplification (LAMP) method for detecting the most common species associated with VVC, including , , , and . We evaluated the specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV), and Kappa value of the LAMP method to detect different species, using the conventional culture method and internal transcribed spacer (ITS) sequencing as gold standards and smear Gram staining and real-time Rolymerase Chain Reaction (PCR) as controls.
RESULTS
A total of 202 cases were enrolled, of which 88 were VVC-positive and 114 were negative. Among the 88 positive patients, the fungal culture and ITS sequencing results showed that 67 cases (76.14%) were associated with , 13 (14.77%) with , 5 (5.68%) with , and 3 (3.41%) with other species. Regarding the overall detection rate, the LAMP method presented sensitivity, specificity, PPV, NPV, and Kappa values of 90.91%, 100%, 100%, 93.4%, and 0.919, respectively. Moreover, the LAMP had a specificity of 100% for , , and , with a sensitivity of 94.03%, 100%, and 80%, respectively. Moreover, the microscopy evaluation had the highest sensitivity, while the real-time PCR was less specific for than LAMP. In addition, CHROMagar Candida was inferior to LAMP in detecting (NAC) species.
CONCLUSIONS
Based on the cost-effective, rapid, and inexpensive characteristics of LAMP, coupled with the high sensitivity and specificity of our VVC-associated detection method, we provided a possibility for the point-of-care testing (POCT) of VVC, especially in developing countries and some laboratories with limited resources.
PubMed: 38132760
DOI: 10.3390/jof9121159 -
Cureus Sep 2023Vulvovaginal atrophy (VVA) is a chronic condition resulting from reduced estrogen levels during menopause. The North American Menopause Society and the International... (Review)
Review
Vulvovaginal atrophy (VVA) is a chronic condition resulting from reduced estrogen levels during menopause. The North American Menopause Society and the International Society for the Study of Women's Sexual Health suggested the term "genitourinary syndrome of menopause" (GSM) to indicate the broader aspects of VVA. Breast cancer treatments, such as chemotherapy and endocrine therapy, can induce early and abrupt menopausal symptoms, including GSM, which negatively affects sexual function and the quality of life of the survivors. Vaginal laser therapy has emerged as a safe and effective option for the management of GSM in breast cancer survivors (BCSs). Two main types of lasers, the non-ablative erbium:YAG laser and fractional microablative CO vaginal laser, have been evaluated for GSM treatment. While there are few randomized controlled trials (RCTs) on the subject of BCSs, a wealth of prospective and retrospective studies have highlighted the beneficial effects of vaginal laser therapy on the symptoms of VVA, vaginal health, sexual function, and overall quality of life. More comprehensive research is essential to confirm its enduring effectiveness and safety, with a focus on conducting standardized and meticulously controlled investigations. This study is a narrative review that summarizes clinical trials ranging from the earliest to the most recent ones on laser treatment for GSM in BCSs.
PubMed: 37731685
DOI: 10.7759/cureus.45495 -
Children (Basel, Switzerland) Aug 2023Genital graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT) is an underdiagnosed manifestation of chronic GVHD. Few articles have been... (Review)
Review
Genital graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT) is an underdiagnosed manifestation of chronic GVHD. Few articles have been published in pediatric populations, and there are no established guidelines for the management of this condition in children. This study aims to provide a systematic literature review of the published studies and cases of genital (vulvovaginal) GVHD in girls and adolescents post HSCT, with a focus on the time of diagnosis and clinical manifestations. The authors searched for English-language articles published after 1990, which included full patient details. Thirty-two cases of female patients under 20 years of age were identified. The median time of diagnosis was 381 days (IQR: 226-730 days), and 83% of patients developed Grade 3 vulvovaginal GVHD. Based on these observations, an early pediatric gynecologic examination of these patients, soon within the first year after HSCT, could be suggested for early diagnosis, treatment initiation and prevention of long-term complications.
PubMed: 37761424
DOI: 10.3390/children10091463