Genitourinary syndrome of menopause (GSM) affects a significant percentage of postmenopausal women and manifests as vaginal dryness, irritation, and urinary discomfort, typically treated with vaginal estrogens. Hydrogels are preferred over creams due to their superior comfort and mucoadhesive properties. This study introduces a novel vaginal gel formulation containing hydroxyethyl cellulose (HEC) and estriol-hydroxypropyl-β-cyclodextrin complex (E3-HPBCD) for the treatment of GSM. The estriol (E3) release profile of the gel was evaluated using a Franz diffusion cell system, and its permeability was tested on reconstructed human vaginal epithelium. Biocompatibility was assessed using (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) (MTT), lactate dehydrogenase (LDH) assays, and real-time cell analysis (RTCA) on human skin keratinocyte (HaCaT) cells, which showed increased cell viability and no obvious cytotoxicity. The results indicated that efficient E3 release and satisfactory epithelial permeability with HPBCD provide the bioavailability of E3. These results suggest the potential of the gel as a biocompatible and effective alternative for the treatment of GSM. Further studies are required to assess the long-term safety and clinical efficacy.

Vulvovaginal symptoms affect up to 39% of women. These symptoms have a significant impact on quality of life and are often linked to imbalances in the vaginal microbiota. This study evaluates the therapeutic efficacy of a zinc-containing hydroxyethyl cellulose-based hydrogel in 37 women with different vulvovaginal symptoms (itching, burning, irritation, pain, dryness, discharge, and odor). Over 12 weeks, participants applied the gel intravaginally with both assessments conducted at baseline and follow-ups. Results revealed substantial improvements in symptoms, including reductions in vaginal discharge, itching, and burning, as measured by the Vulvovaginal Symptom Questionnaire (VSQ-21), with scores decreasing from 10.78 ± 3.66 at baseline to 3.17 ± 4.16 at week 12 (p < 0.01). Vaginal Health Index (VHI) scores improved significantly, from 20.78 ± 1.74 at baseline to 23.64 ± 2.59 (p < 0.01). Cervicovaginal lavage (CVL) zinc levels decreased from 110 ± 102 µg/L at baseline to 62 ± 48 µg/L at week 4 (p < 0.01), increased to 80 ± 55 µg/L at week 8 (p = 0.04), and reached 99 ± 92 µg/L by week 12 (NS). A correlation analysis showed an inverse relationship between baseline CVL zinc levels and VSQ-21 scores (r = −0.3586, p = 0.034), while no significant correlation was observed with VHI scores (r = −0.0187, p = 0.9545). Vaginal pH levels decreased significantly, dropping from 4.03 ± 0.42 to 3.71 ± 0.48 (p < 0.01). These findings support the gel’s role as an effective, nonhormonal, drug-free, and local adjunct treatment for a variety of vulvovaginal symptoms.

Menopause is frequently associated with cognitive complaints, including difficulties with memory, concentration, and executive functioning. Pyrroloquinolin

Transition metals such as iron and manganese are critical for cellular metabolism, redox balance, and immune function, and they also influence host–pathogen interactions. Vaginitis is characterized by mucosal inflammation that may alter local trace-element homeostasis. We hypothesize that inflammatory conditions such as vaginitis may be associated with altered cervicovaginal iron and manganese levels. We performed a prospective, single-center cohort study at the University of Debrecen (Hungary) between April 2023 and April 2024, enrolling 80 women ≥ 18 years with vulvovaginal complaints. Participants were assessed at baseline and at weeks 4, 8, and 12 with clinical evaluation and cervicovaginal lavage (CVL) sampling, collected using metal-free instruments. Participants were randomized 1:1 to receive either fluconazole alone or a single baseline oral fluconazole plus an intravaginal zinc-containing hydrogel. CVL samples were digested and analyzed for iron and manganese using ICP-OES. Group comparisons were performed using linear mixed-effects models with a random intercept for participant. CVL Fe concentrations were higher in women with culture-positive vaginitis compared with controls (mean ± SD: 56.36 ± 24.84 vs. 44.64 ± 20.11), with a significant between-group difference in mixed-effects models (Δ = 8.82, 95% CI 0.74 to 16.89; p = 0.032). Mn concentrations did not differ between vaginitis and controls (1.42 ± 0.73 vs. 1.09 ± 0.77; p = 0.542). In subgroup analyses, Fe remained significantly higher in vaginitis compared with controls among women who did not use the hydrogel (60.69 ± 26.53 vs. 47.27 ± 21.87; p = 0.041), whereas the difference was attenuated and no longer significant among hydrogel users (53.64 ± 23.62 vs. 41.75 ± 17.71; p = 0.148). Within the vaginitis cohort, Fe and Mn concentrations were similar across culture-defined phenotypes (bacterial-positive vs. fungal-positive) and between fungal culture-negative and fungal-positive samples. Culture-positive vaginitis was associated with higher total cervicovaginal iron concentrations, while manganese remained largely unchanged. Adjunct topical zinc therapy appeared to temper the vaginitis-associated elevation in iron, consistent with improved mucosal integrity and reduced inflammation-driven iron availability. Total Fe and Mn concentrations in CVL did not distinguish vaginitis phenotypes, supporting their use primarily as reference values and motivating future work focused on bioavailable metal fractions and metal-binding host proteins. The study protocol was approved by the Hungarian National Institutional Review Medical Research Council (approval No. 3282-7/2023/EUIG).

Background: Recurrent and persistent vulvovaginal candidiasis remain clinically challenging, and supportive strategies that improve post-treatment microbiological stability are needed. Zinc-containing vaginal hydrogel may influence local host–pathogen interactions, but clinical data on its adjunctive use after fluconazole are limited. Methods: This single-center, two-arm, parallel-group randomized clinical trial compared standard oral fluconazole therapy alone with fluconazole followed by adjunctive zinc-containing vaginal hydrogel. Women with symptomatic acute vulvovaginal candidiasis were assessed at baseline, week 4, week 8, and week 12. The primary outcome was clinical cure, defined as Candida Severity Score < 3. Secondary outcomes included symptom severity, Vaginal Health Index, mycological cure, and interim antifungal treatment. A post-clearance recurrence cohort included participants with both clinical and mycological clearance at week 4. Results: Fifty-four women were included in the modified intention-to-treat cohort: 22 controls and 32 hydrogel-treated participants. Clinical cure did not differ significantly between groups at week 4, week 8, or week 12. Longitudinal models showed no significant group-by-time interaction for clinical cure, Candida Severity Score, Vaginal Health Index, VSQ-21, or interim antifungal treatment. At week 12, mycological cure was numerically more frequent in the hydrogel group than in controls, without reaching statistical significance (65.6% vs. 40.9%; OR = 2.76, 95% CI 0.90–8.45; p = 0.097). In the exploratory post-clearance recurrence cohort, week-12 culture negativity was observed in 14/14 hydrogel-treated participants and 11/17 controls (100.0% vs. 64.7%; p = 0.021), corresponding to microbiological culture recurrence rates of 0.0% and 35.3%, respectively. Conclusion: Adjunctive zinc-containing vaginal hydrogel following oral fluconazole was not associated with a significant improvement in acute clinical cure in the overall study population. The observed maintenance of fungal culture negativity among women with documented early clinical and mycological clearance should be interpreted as an exploratory microbiological signal rather than definitive evidence of clinical recurrence prevention. Larger placebo-controlled trials specifically designed and powered for recurrent vulvovaginal candidiasis and culture-confirmed recurrence are needed. The study protocol was approved by the Hungarian National Institutional Review Medical Research Council (approval No. 3282-7/2023/EUIG). All participants provided written informed consent before any study-related procedure. The trial was registered at ClinicalTrials.gov (NCT05895162; registration date: 15 May 2023).

Zinc (Zn) and copper (Cu) support epithelial integrity, nutritional immunity, and host–microbiome interactions, yet cervicovaginal trace-metal dynamics across vaginitis phenotypes remain poorly defined. We prospectively quantified cervicovaginal lavage (CVL) Zn and Cu by ICP-OES in an exploratory secondary analysis nested within a single-center randomized trial involving 56 symptomatic women and asymptomatic controls (mean age, 36.0 ± 11.8 years; mean BMI, 23.1 ± 4.9 kg/m²). We examined whether CVL trace-element concentrations varied according to culture-defined phenotype and randomized hydrogel exposure. CVL Zn concentrations were higher in the Candida albicans-positive (120.2 ± 95.6 µg/L) and symptomatic culture-positive bacterial phenotypes (83.8 ± 55.2 µg/L) than in controls (58.6 ± 27.2 µg/L), whereas Cu showed less consistent variation. Among participants assigned to hydrogel, phenotype-specific differences from controls were not statistically significant. In the fluconazole-only group, higher Zn concentrations were observed in the C. albicans-positive phenotype (154.3 ± 113.5 vs. 54.2 ± 23.8 µg/L), accompanied by higher Cu concentrations (12.13 ± 4.76 vs. 5.76 ± 2.86 µg/L). These exploratory findings indicate that cervicovaginal trace-element profiles may vary across symptomatic culture-defined phenotypes and treatment groups. Our findings should be interpreted as hypothesis-generating. Biological and clinical relevance remains uncertain and warrants confirmation in adequately powered, longitudinal studies using dilution-normalized CVL measurements. Trial registration: The study protocol was approved by the Hungarian National Institutional Review Medical Research Council (approval No. 3282-7/2023/EUIG). The parent trial is registered at ClinicalTrials.gov (NCT05895162; 2023-05-15). Each participant signed a written informed consent form. All procedures performed in studies involving human participants were under the ethical standards of the Hungarian National Institutional Review Medical Research Council and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.