Artificial intelligence and machine learning in smart vaginal formulation development.

Imbalances in the vaginal flora during pregnancy elevate risks for adverse outcomes. While nifuratel targets pathogens, probiotics restore acidity, and robust cohort evidence supporting their combined safety and efficacy in restoring the microbiome remains limited. This retrospective cohort study assessed nifuratel-nystatin therapy plus Lactobacillus probiotics for restoring vaginal flora in pregnancy. Employing a retrospective cohort design, this study enrolled pregnant women diagnosed with vaginal microecological abnormalities between March 2023 and 2024. Participants were allocated via 1:1 propensity score matching (PSM) into two groups (n=58 each): a combination group receiving nifuratel-nystatin therapy combined with vaginal Lactobacillus probiotics and a monotherapy group receiving nifuratel-nystatin alone. All received a 7-day treatment. The primary endpoint was clinical effectiveness assessed one week post-treatment. Secondary outcomes included vaginal pH, Lactobacillus and bacterial diversity normalization rates, recurrence, adverse pregnancy outcomes and drug-related adverse events, monitored until delivery. Multivariate logistic regression identified independent predictors of treatment efficacy. After PSM, baseline characteristics were balanced (P>0.05). The comparative analysis indicated a superior overall efficacy for the combination therapy (93.1%) over monotherapy (77.6%), with statistical significance (P<0.01) Both groups exhibited reduced vaginal pH and increased rates of normalized Lactobacillus and bacterial diversity, with greater improvements observed in the combination group (P<0.01). The recurrence rate was significantly lower in the combination group (8.6% vs. 22.4%; P<0.05), as was the total incidence of adverse pregnancy outcomes (6.9% vs. 20.7%; P<0.01). No significant difference in adverse drug reactions was found. Multivariate analysis identified combination therapy as an independent protective factor for clinical efficacy (aOR=4.25, 95% CI: 1.42-12.71, P<0.05). In pregnant women with vaginal dysbiosis, combining nifuratel-nystatin with Lactobacillus probiotics safely enhances clinical efficacy, normalizes pH and flora and reduces adverse pregnancy outcomes.

CST-Based Molecular Profiling of Vaginal Microbiota Validated by qRT-PCR and 16S Amplicon Sequencing.

Development of a pH-modulating vaginal film through direct powder extrusion 3D printing for on-demand, hormone-free contraception: a quality by design approach.

BackgroundTestosterone-associated vulvovaginitis is an under-recognised cause of genital symptoms in transmasculine patients receiving testosterone as gender-affirming hormone therapy, with 5-years prevalence 64-78%. BASHH's Gender and Sexual Minorities Special Interest Group convened sexual health, gender, gynaecological and primary care experts and patient representatives to formulate a first-in-world best practice statement.MethodWe searched Medline, Embase, CINAHL, UpToDate, Trip Medical Database and Cochrane, to April 2025, regarding testosterone's impact on transmasculine people's vaginal histology and microbiomes, symptoms, and management. Papers on cis- or transgender women, editorials, and study protocols were excluded. Included studies were assessed using the Critical Appraisal Skills Programme tool. Recommendations for best practice were graded using GRADE methodology where possible, and supplemented by expert group consensus where evidence was limited.Results14 papers were included, of which 11 were descriptive/non-management focused. Testosterone is associated with vaginal Lactobacilli depletion, increased speciation, pH changes, atrophy, inflammation, and epithelial cell differentiation shift. The diagnosis of testosterone-associated vulvovaginitis is clinical; symptom severity does not reliably correlate with any of the above, nor other markers such as hormone levels. Two small case series and one cohort study (total n = 12) discussed treatment; topical estrogen reduced vaginal symptoms and increased Lactobacilli, with some refractory inflammatory cases requiring topical clindamycin +/- topical steroids. Presumed efficacy and safety are extrapolated from topical estrogen use in cisgender menopausal women.ConclusionSpecific evidence for testosterone-associated vulvovaginitis management is lacking; we suggest a culturally competent approach, considering it as a differential in any transmasculine people on testosterone with genitourinary symptoms. Offer examination (if possible) to exclude infection or dermatoses; offer first-line treatment with topical vaginal estrogens. Adjunctive/alternative measures include emollients and lubricants; topical clindamycin +/- topical steroids for refractory cases or aerobic/desquamative vaginitis. Long-term maintenance therapy and review is advised. Robust trans-specific clinical trials are needed to strengthen the evidence and optimise long-term outcomes.

The effect of hormone therapy on vaginal microbiota in women with genitourinary syndrome of menopause: A double-blind, randomized, placebo-controlled trial.

This meta-analysis systematically evaluated the effects of probiotic supplementation on vaginal microbiota and inflammatory factors in women. PubMed, Embase, Web of Science, CNKI, and Wanfang were searched from inception to January 2026 for randomized and controlled studies. Outcomes included vaginal pH, Nugent score, and inflammatory cytokines (IL-4, IL-6, IL-10, TNF-α). Fifteen studies were included. Compared with controls, probiotics did not significantly reduce IL-4, IL-6, IL-10, or TNFα levels, nor did they significantly improve Nugent score. However, probiotic supplementation significantly reduced vaginal pH (OR = 0.36, 95% CI: 0.15-0.89; P = 0.03), indicating improved maintenance of a weakly acidic vaginal environment. Sensitivity analyses showed generally stable results, although heterogeneity remained substantial for several outcomes. Overall, probiotics appear effective in modulating vaginal acid-base balance but show limited evidence for improving inflammatory cytokine profiles or restoring vaginal microbiota structure. Current data are insufficient to support routine probiotic use for optimizing vaginal microbiota and inflammatory status. Further high-quality, well-designed randomized controlled trials are required to clarify their clinical benefits.

Background:The vagina undergoes important changes across the life course that are shaped not only by hormonal transitions but also by shifts in the vaginal microbial environment. Despite growing interest in the vaginal microbiome, research has disproportionately centered reproductive-aged populations, leaving the aging vagina comparatively understudied.Objective:This article examines the aging vagina through a life-course lens, with emphasis on microbial and clinical transitions associated with midlife and older adulthood.Key Content:The article highlights menopause-related changes and approaches for reducing stigma and missed clinical opportunities. Particular attention is given to menopause-related declines in estrogen, reduced glycogen availability, increased vaginal pH, and accompanying changes in microbial balance, as well as their relationship to dryness, irritation, genitourinary symptoms, and susceptibility to adverse outcomes. The article also provides health professionals with a practical educational framework for symptom recognition, patient communication, vaginal health assessment, menopause-related education, stigma reduction, and prevention of missed clinical opportunities.Conclusions:Positioning the aging vagina within life-course and microbial-health frameworks can strengthen prevention, improve symptom recognition, and support more ageinclusive, informed, and responsive care for older women.

The primary objective was to evaluate the efficacy of vaginal dehydroepiandrosterone (DHEA) and estradiol (E2) on dyspareunia, a symptom of vulvovaginal atrophy (VVA) in postmenopausal women. In an open-label, randomized controlled trial, 172 naturally postmenopausal women with a mean age of 62.4±5.7years and moderate or severe dyspareunia caused by VVA, received DHEA (6.5mg pessaries) or E2 (10μg vaginal tablets) daily for 4weeks and then twice-weekly up to 12weeks. Symptoms and signs of VVA were assessed at baseline, week 4 and 12 of treatment. The primary outcome was the proportion of patients in each treatment group achieving an improvement of 1 point or more in dyspareunia score on a 4-point scale (none, mild, moderate, severe). Secondary outcomes included other symptoms and objective signs of VVA. Women in both groups had improved in dyspareunia by week 12 (DHEA 92% and E2 82%), with a tendency of significant difference between the groups (OR 2.87, 95% CI 1.00-8.25; p=0.051). For those with severe dyspareunia at baseline there was higher odds of improvement in the DHEA group than in the E2 group (OR 3.4, 95% CI 1.07-10.5). Vaginal pH, maturity index, and total score for clinical signs of atrophy improved more in the E2 group than in the DHEA group. Vaginal DHEA tended to improve dyspareunia more than E2 and was superior in alleviating severe dyspareunia in postmenopausal women. On the other hand, vaginal E2 was superior in improving clinical subjective and objective signs of VVA. gov registration number NCT05586711.

Effect of Lactobacillus-based probiotics on genitourinary syndrome of menopause in post-menopausal women: A systematic review.

Cervical cancer poses a serious threat to women's health. Emerging evidence indicates that changes in the cervicovaginal microbiota (CVM) and vaginal microenvironment may play a crucial role in cervical carcinogenesis. In this study, we examined CVM and vaginal microenvironment profiles in 510 participants with varying stages of cervical lesions using 16S rRNA sequencing, vaginal pH and H2O2 measurements, and cleanness assessment. A co-occurrence network and generalized multifactor dimensionality reduction model were employed to analyze the correlation and interaction between microbial taxa and microenvironment profile. Our results demonstrated that CVM disorder and abnormal vaginal microenvironment were associated with cervical lesions. As cervical cancerization progressed, the abundance of Lactobacillus gradually decreased with thriving anaerobe levels in the deteriorating vaginal microenvironment. This interaction was characterized by high vaginal pH, a non-Lactobacillus-dominant microbiota, and high CVM diversity (Shannon index ≥ 0.81). Co-occurrence network analysis revealed that abnormal pH and H2O2 levels correlated with Lactobacillus depletion and had a positively co-occurring relationship with anaerobes in precancerous cervical lesions. CVM function significantly varied with changes in the vaginal microenvironment across different stages of cervical lesions. Our findings suggest that CVM dysbiosis, particularly when combined with an abnormal vaginal microenvironment, may promote the progression of cervical lesions. This highlights the importance of addressing vaginal microecology to prevent cervical carcinogenesis.IMPORTANCECervicovaginal microbiota (CVM) and vaginal microenvironment in human papillomavirus infection are associated with the progression of cervical carcinogenesis. CVM dysbiosis, particularly the decrease in Lactobacillus and the increase in anaerobes, is crucial in promoting the malignant progression of cervical lesions. As cervical carcinogenesis progresses, the relative abundance of anaerobes increases in the deteriorating vaginal microenvironment. We systematically analyzed the relationship between CVM and the vaginal microenvironment in cervical lesions, aiming to reveal the contribution of CVM with specific vaginal microenvironmental features and its functional changes in the progression of cervical carcinogenesis. Our results may provide new insights into the etiology and pathogenesis of cervical cancer from the perspective of vaginal microecology.

The objective of the study is to evaluate symptom improvement, safety, tolerability, and patient satisfaction associated with a hyaluronic acid-based internal vaginal moisturizer in women with symptomatic vaginal dryness under real-world conditions. This prospective, multicenter, single-arm, open-label post-market clinical investigation was conducted in outpatient gynecology clinics in Spain between June and September 2022. Fifty-one women aged ≥18 years with symptomatic vaginal dryness were enrolled; 48 comprised the intention-to-treat population. Participants self-administered a CE-marked hyaluronic acid-based vaginal moisturizer three times weekly for six weeks. The primary endpoint was the change from baseline to week 6 in vaginal dryness severity measured using a non-validated 10-point visual analogue scale (VAS). Secondary endpoints included changes in irritation, itching, dyspareunia, vaginal hydration, vaginal pH, safety, and patient satisfaction. Within-subject changes were analyzed using paired comparisons. In participants with paired baseline and week 6 data (n = 47), mean vaginal dryness severity decreased from 7.34 ± 2.20 to 3.47 ± 2.00. The mean change was -3.87 points (95% confidence interval (CI) -4.62 to -3.12; t = -10.5; p < 0.001), corresponding to a large within-subject standardized effect size (Cohen's dz = 1.54). Significant reductions were also observed for irritation (-2.11; n = 47), itching (-2.16; n = 45), and dyspareunia (-2.88; n = 42) (all p < 0.001). Vaginal hydration increased (+2.69; p < 0.001), and vaginal pH decreased modestly (-0.44; p = 0.001). Eight of 48 participants (16.7%) reported device-related adverse events, all mild to moderate; no serious adverse events occurred. Three participants discontinued due to adverse events. In this prospective, real-world, single-arm clinical investigation, use of a hyaluronic acid-based vaginal moisturizer was associated with significant short-term reductions in vaginal dryness and related symptoms, with an acceptable safety profile. Given the absence of a comparator group, results should be interpreted cautiously. Findings should be considered hypothesis-generating.

Background/Objectives: Compounded vaginal creams are widely used for conditions such as hormone replacement therapy, vaginal dryness, low libido, vaginal infections, etc. Recent research highlights the potential of using anhydrous bases to extend shelf life, particularly when combined with self-emulsifying and mucoadhesive properties that improve mucosal retention and enhance drug bioavailability. This study provides in vitro and ex vivo evaluation of an anhydrous vaginal base. Methods: Key quality indicators such as irritation potential, leakage potential, pH compatibility, mucoadhesion, and self-emulsification were assessed using the chorioallantoic membrane Hen's Egg Test, MTT assay, texture analysis, and fluorescence microscopy. Results: The anhydrous vaginal base demonstrated high cell viability (>78%) and non-irritant potential (IS = 2.5) in in vitro assays. It maintained physiological vaginal pH (4.56 ± 0.05), showed strong mucoadhesive properties comparable to commercial products, and exhibited minimal leakage. Ex vivo studies confirmed its prolonged retention on vaginal tissues. The anhydrous vaginal base formed stable emulsions upon contact with vaginal fluid simulant, effectively distributing both lipophilic and hydrophilic compounds. Conclusions: Compared to water-containing bases, an anhydrous vaginal base shows advantages: longer retention time and lower leakage; adaptability to varying vaginal fluid levels; and efficient dispersion of both hydrophilic and lipophilic active pharmaceutical ingredients. These features support its potential use in compounded vaginal products, minimizing stability risks and enhancing patient compliance and therapeutic outcomes.

Effect of a non-hormonal vaginal moisturizer on vaginal and vulvar health in postmenopausal women with breast cancer: A randomized clinical trial.

Females influence offspring paternity through diverse pre- and post-copulatory mechanisms. Sperm discrimination—the differential physiological response to ejaculates based on male or sperm characteristics—can bias fertilization outcomes, but in vivo evidence of this process in large-bodied mammals is lacking. Here, in a study of nine females and four males, we tested whether two aspects of female physiology that affect sperm survival—vaginal immune response and pH—are modulated by male genetic makeup in a non-human primate, the olive baboon (Papio anubis). Our findings suggest post-copulatory differences in vaginal gene expression and pH, with the strongest immune responses and largest pH decreases, harmful to sperm, exhibited by females mating with genetically similar males. These findings are consistent with genetically-based post-copulatory mate discrimination, offering new insights into how interactions between male gametes and the female reproductive tract may shape conception probability in primates.

The objective: to evaluate the clinical and microbiological efficacy, as well as the impact on tissue repair processes, of D-xylitol prebiotic vaginal capsules during the pre- and postoperative periods in patients undergoing surgical correction of pelvic organ prolapse and stress urinary incontinence.Materials and methods. A comparative, open-label, randomized study was conducted involving 144 women (mean age 55.5 ± 3.2 years) with pelvic organ prolapse and/or stress urinary incontinence. The patients were divided into 4 clinical groups based on their baseline vaginal microbiocenosis (according to the Hay/Ison criteria) and the prescribed treatment regimen. Clinical symptomatology, vaginal pH dynamics, bacterioscopy and quantitative real-time polymerase chain reaction (qPCR) results, as well as the incidence of long-term postoperative complications (over a 6-month monitoring period) were evaluated.Results. The use of the prebiotic complex with D-xylitol contributed to the rapid resolution of symptoms and the normalization of vaginal pH. According to qPCR data, the mean proportion of Lactobacillus spp. in the groups receiving D-xylitol increased to 85.2 ± 3.4%, which significantly exceeded the indicators of the groups not receiving D-xylitol (57.4 ± 4.2%). 6 months postoperatively, patients in the groups receiving D-xylitol did not have a single case of suture separation or erosion of alloimplants, while in the groups not receiving this drug, the rate of suture dehiscence was 2.8%, and polypropylene mesh erosion occurred in 3.0–5.6% of cases. The compliance ranged from 82.8% to 87.1%.Conclusions. The local peri- and postoperative application of D-xylitol prebiotic capsules (“Mastrelle Flora Plus”) demonstrates a high efficacy in restoring vaginal normocenosis and significantly reduces the risk of infectious and reparative complications in vaginal surgery.

Background: Genitourinary syndrome of menopause (GSM) affects approximately 50% of postmenopausal women and arises from estrogen deficiency, causing vaginal epithelial thinning, Lactobacillus depletion, and increased vaginal pH, which collectively elevate infection risk. Local estrogen therapy (LET) is standard but may be limited. Interest is growing in non-hormonal regenerative therapies, including CO₂ and Er:YAG lasers and PRP. Aim: This narrative review aims to evaluate the current evidence on the efficacy and safety of CO₂ and Er:YAG laser therapies, as well as platelet-rich plasma (PRP), in the management of GSM with a focus on clinical guidelines and expert recommendations. Methods: A narrative review of the literature was conducted, including clinical trials, systematic reviews, expert opinions, and international society guidelines. Outcomes of interest included symptom severity (VAS), Vaginal Health Index (VHI), Female Sexual Function Index (FSFI), vaginal pH, patient satisfaction, and reported adverse events. Results: CO₂ and Er:YAG laser therapies, as well as PRP, demonstrate promising efficacy in reducing symptoms of genitourinary syndrome of menopause, with improvements observed in clinical parameters (VHI, FSFI, VAS) and high patient satisfaction. The safety profile reported in available studies is favorable, with adverse events generally mild and transient. Conclusions: CO₂ and Er:YAG laser therapies and PRP represent promising non-hormonal approaches for GSM, particularly in women with contraindications to estrogen. Due to limited high-quality evidence, these modalities remain experimental, and their efficacy and protocols require confirmation in long-term, sham-controlled studies.

Perimenopause, menopause, and postmenopause are stages characterized by hormonal changes that can cause vasomotor symptoms, menstrual alterations, and genitourinary manifestations. These modifications in the vaginal mucosa and pH increase the risk of urinary tract infections (UTIs). Although pharmacological treatment is the most common approach, multiple preventive strategies are available. The aim of this review was to analyze the scientific literature on UTI prevention and assess its effectiveness in women during perimenopause and postmenopause. A bibliographic search was conducted in PubMed, CINAHL, PEDro, Web of Science, and Scopus using the terms urinary tract infections, menopause, premenopause, and postmenopause. Randomized controlled trials published in Spanish, English, Portuguese, and Italian were included. A total of 2,777 studies were identified, of which 8 met the eligibility criteria. The included trials evaluated hormonal, pharmacological, and natural prophylactic interventions. The primary outcome was the number of UTI episodes, measured through diagnostic tests or clinical symptoms. Various prophylactic options (hormonal, pharmacological, and natural) have proven effective in reducing the incidence of UTIs in perimenopausal and postmenopausal women. The choice of preventive strategy should also take into account additional clinical and safety variables.

During pregnancy, vaginal flora pH changes and vaginal discharge may increase. Pregnant women may resort to traditional methods for vaginal discharge, but some traditional practices may cause health problems. This study aimed to examine the attitudes of pregnant women in Turkey towards traditional and complementary medicine attitude and the traditional practices they use for abnormal vaginal discharge. This descriptive study was conducted with 306 pregnant women using an online survey via social media platforms. The Personal Identification Form and the Complementary, Alternative and Conventional Medicine Attitudes Scale were used as data collection tools. 60.5% of participants had not received genital hygiene education. 15% of participants used traditional and complementary medicine methods for vaginal discharge, and 57.1% of those who used these methods used niaouli oil. The mean score obtained from the Complementary, Alternative and Conventional Medicine Attitudes Scale was 106.32 ± 21.76. The attitude scores of non-working participants were significantly higher than those of working participants (p = 0.018). Participants who had fewer than four prenatal visits and those who did not receive genital hygiene education had higher total scale scores (p = 0.001 and p = 0.026). Additionally, visiting a doctor when experiencing abnormal vaginal discharge was found to negatively affect the total scale score (p = 0.010). Pregnant women’s attitudes toward traditional and complementary medicine practices were generally moderate, while the rates of using traditional and complementary medicine methods for vaginal discharge and receiving genital hygiene education were low. Therefore, it is recommended that healthcare professionals inquire about pregnant women’s use of CAM methods during prenatal checkups, provide genital hygiene education, and incorporate CAM methods into prenatal education programs based on evidence-based information.

ObjectiveTo investigate the correlation between vaginal microbiota indicators and HPV infection, providing a reference for clinical prevention and treatment of HPV-related diseases.MethodsClinical data of 5,362 female patients who underwent vaginal microbiota testing and HPV detection were retrospectively analyzed. The distribution of vaginal microbiota indicators and their association with HPV infection were statistically analyzed using the chi-square test. Three hundred fifty-five patients infected with HPV 16/18 were enrolled, followed up their HPV re-detection results at 12 months, and performed univariate analysis and logistic regression analysis to identify the risk factors for persistent HPV infection.ResultsAmong the 5,362 subjects, the positive rates of hydrogen peroxide, sialidase, leukocyte esterase, Trichomonas vaginalis, mold, and clue cells were 96.38%, 16.51%, 59.29%, 0.93%, 16.09%, and 8.65% respectively. 63.19% of the subjects had vaginal cleanliness of III-IV, and 71.73% had a vaginal pH value >4.5. Statistical analysis showed that sialidase (χ2 = 4.13, P = 0.04), and vaginal cleanliness (χ2 = 8.32, P = 0.00) were significantly associated with HPV infection; Vaginal Cleanliness(χ2 = 8.32, P = 0.04) and pH(χ2 = 14.63, P = 0.00) were significantly associated with HPV Genotypes. Vaginal pH value (OR = 2.65, 95% CI: 1.55–4.52, P < 0.001), N-acetylglucosaminidase positive (OR = 2.14, 95% CI: 1.12–4.08, P = 0.021), and fungus detected (OR = 1.88, 95% CI: 1.06–3.35, P = 0.032) were identified as independent risk factors for persistent HPV infection.ConclusionVaginal microbiota imbalance, as indicated by abnormal sialidase, poor vaginal cleanliness, and elevated pH value, may be related to HPV infection. Vaginal pH value, N-acetylglucosaminidase positive and fungus detected were identified as independent risk factors for persistent HPV infection.