Berberine-fluconazole microparticle-based combination therapy to treat candidiasis infections.

AIM: This study aims to incorporate alginate microparticles containing berberine and fluconazole into two different types of pharmaceutical formulations, to subsequently evaluate the antifungal activity against Candida albicans. METHODS AND RESULTS: Alginate microparticles containing BBR (berberine) and FLU (fluconazole) were produced by the spray-drying technique, characterized and incorporated in two pharmaceutical formulations, a vaginal cream and artificial saliva. Broth microdilution, checkerboard, time-kill curve, and scanning electron microscopy were carried out to determine the antifungal effects of BBR and FLU against C. albicans. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values of free BBR were 125 µg ml-1. Synergism between BBR and FLU was demonstrated by a fractional inhibitory concentration index (FICI) = 0.0762. The time-kill curve for the combination BBR + FLU showed a more pronounced decrease in fungal growth in comparison to free drugs, and an antibiofilm effect of BBR occurred in the formation and preformed biofilm. CONCLUSION: Alginate microparticles containing BBR and FLU were obtained and incorporated in a vaginal cream and artificial saliva. Both formulations showed good stability, antifungal effects, and organoleptic characteristics, which suggest that BBR-FLU microparticles in formulations have potential as antifungal therapy.

The efficacy of complementary treatment with marshmallow (Althaea officinalis L.) on vulvovaginal candidiasis: A randomized double-blinded controlled clinical trial.

BACKGROUND: Vulvovaginal candidiasis is a common gynecologic infection, and recurring cases are yet incurable. This trial was based on Persian medicine to compare how effective marshmallow aqueous extract 4% plus clotrimazole 1% (CLOT-M) is compared to clotrimazole 1% vaginal creams on VVC. METHODS: This study randomly assigned 100 women with VVC into two groups. The target group (n = 50) was treated with CLOT-M while controls (n = 50) with clotrimazole vaginal creams for seven consecutive nights. Different VVC symptoms and signs, and yeast culture from vaginal discharge were evaluated as the outcome measures before the intervention and 7 and 30 days after. RESULTS: The efficacy of CLOT-M vaginal cream was assessed during the 1st and 2nd follow-ups, indicating a significant decrease in mean itching (P = 0.001 for both comparisons) and dyspareunia score (P = 0.001 and P = 0.04, respectively) as compared to treatment with clotrimazole vaginal cream. Moreover, after 7 days of the intervention, patients in the CLOT-M group experienced significant improvement in mean dysuria score compared to those in the control group (P = 0.001). Neither cream caused any significant adverse events. CONCLUSION: It seems that CLOT-M vaginal cream had a significant effect on the VVC symptoms improvement, without any significant side effects. However, larger sample-sized trials are needed for more evidence-based judgment.

The effect of nettle vaginal cream on subjective symptoms of vaginal atrophy in postmenopausal women.

BACKGROUND AND OBJECTIVE: Vaginal atrophy is a condition where the vaginal epithelium gets thinner and includes symptoms, such as vaginal dryness, abnormal vaginal discharge, vaginal bleeding, dyspareunia, and sexual problems. Hormone therapy is associated with some problems and some women prefer herbal medicine to reduce vaginal atrophy. Considering the phytoestrogenic compounds present in the nettle, this study aimed to investigate the effect of the nettle vaginal cream on subjective symptoms of vaginal atrophy in postmenopausal women. MATERIALS AND METHODS: This triple-blind randomized placebo-controlled clinical trial study was conducted on 84 eligible postmenopausal women aged 45-60 years, who referred to comprehensive health service centers in Aliabad Katul in 2021-2022. Women eligible for the study received 5% nettle vaginal cream and placebo for 8 weeks. Subjective symptoms of vaginal atrophy were assessed before, four and eight weeks after the intervention. Data collection tools included a checklist for research unit selection, individual and midwifery characteristics questionnaire, vaginal assessment scale (VAS), vaginal pH, laboratory results of the vaginal maturation value (VMV). Data analysis was performed using SPSS software (version 21) and independent t-test, Mann-Whitney, chi-square, Two-way analysis of variance and analysis of covariance. P value less than 0.05 was considered significant. RESULTS: Subjective symptoms of vaginal atrophy decreased significantly after the intervention compared to before the intervention in both the nettle and placebo groups (p < 0.001), but in the comparison between groups four weeks and eight weeks after the intervention, the subjective symptoms of vaginal atrophy in nettle group decreased significantly (p < 0.001). In the nettle group, the scores of vaginal burning, vaginal dryness, vaginal itching and dyspareunia significantly improved after the intervention compared to before the intervention (p < 0.001). Also, in the nettle group compared to the placebo group, after the intervention, vaginal burning and vaginal dryness score (p < 0.001) and vaginal itching score (0.004) improved significantly. CONCLUSION: Based on the results of the present study, Nettle vaginal cream reduced subjective symptoms of vaginal atrophy, including vaginal burning, vaginal dryness, vaginal itching, and dyspareunia in postmenopausal women, so it is a cost-effective, available and do not have the side effects product that can be useful for menopausal women.

Improved treatment of vulvovaginal candidiasis with Clotrimazole plus probiotic Lacidophilin Vaginal Capsules: A prospective, real-world study.

BACKGROUND: Clotrimazole has long been used to treat vulvovaginal candidiasis (VVC), yet the antibiotic resistance, adverse effects and recurrences still bring about a great challenge for the clinicians. To explore the effect of probiotic Lacidophilin Vaginal Capsules plus Clotrimazole Vaginal Tablets (500mg) in the treatment of uncomplicated VVC, a self-controlled real-world study was conducted. METHODS: Twenty-seven women with a normal vaginal flora and 15 women with uncomplicated VVC were recruited. The patients were treated with the single dose of Clotrimazole Vaginal Tablets (500mg) supplemented with 2 Lacidophilin Vaginal Capsules for the following 7 days. The patients were prospectively examined 4 times and the time points were at m0 (the first visit), m1 (8-10 days after the first visit), m2 (30 days after the second visit) and m3 (30 days after the third visit). However, women in the healthy normal control group were examined just once at the first visit. The obtained vaginal secretions were examined by high-throughput sequencing. RESULTS: The mean age in healthy control group and case group was 28.63 ± 5.40y and 27.67 ± 3.33y, respectively. Finally, 46.67% (7/15) of patients were cured at the second visit, 61.54% (8/13) were cured at the third visit and eventually 72.73% (8/11) were cured. A total of 81 samples were sequenced, generating 1668 operation taxonomy units among all the samples. The bacterial composition of women in the healthy control group was exceedingly abundant and dominated by Lactobacillus, especially by Lactobacillus. crispatus, and followed by Lactobacillus. iners, Lactobacillus. jensenii and Gardneralla. On the contrary, the bacterial composition of women with VVC was relatively few and dominated by Lactobacillus. iners. During the process of treatment, the bacterial abundance of VVC patients was increased gradually. At the final visit, the abundance of vaginal flora was augmented further with the dominant bacteria being Lactobacillus. crispatus, followed by Lactobacillus. iners. CONCLUSION: Clotrimazole Vaginal Tablets plus probiotic Lacidophilin Vaginal Capsules could improve the effect in treating uncomplicated VVC. This improved effect was achieved perhaps through improving the composition of vaginal flora and restoring vaginal microecology.

Progesterone supplementation in natural cycles improves live birth rates after embryo transfer of frozen-thawed embryos-a randomized controlled trial.

STUDY QUESTION: Does supplementation with vaginal tablets of progesterone after frozen-thawed embryo transfer in natural cycles improve the live birth rate? SUMMARY ANSWER: Supplementation with vaginal tablets of progesterone after frozen-thawed embryo transfer in natural cycles significantly improves the number of live births. WHAT IS KNOWN ALREADY: Progesterone supplementation during luteal phase and early pregnancy may improve the number of live births after frozen-thawed embryo transfer. However, due to the limited number of previous studies, being mainly retrospective, evidence is still limited. STUDY DESIGN, SIZE, DURATION: This is a prospective randomized controlled trial, performed at two university clinics. In total, 500 subjects were randomized with a 1:1 allocation into two groups, during the period February 2013 to March 2018. Randomization was performed after a frozen embryo transfer in a natural cycle by use of opaque sealed envelopes. The primary outcome was live birth rate; secondary outcomes were pregnancy, biochemical pregnancy, clinical pregnancy and miscarriage rate, and if there was a possible association between the serum progesterone concentration on the day of embryo transfer and live birth rate. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women, receiving embryo transfer in natural cycles participated in the study. The embryos were frozen on Day 2, 3, 5 or 6. In total, 672 women having regular menstrual cycles were invited to participate in the study; of those, 500 agreed to participate and 488 were finally included in the study. Half of the study subjects received progesterone supplementation with progesterone vaginal tablets, 100 mg twice daily, starting from the day of embryo transfer. The other half of the subjects were not given any treatment. Blood samples for serum progesterone measurements were collected from all subjects on the day of embryo transfer. MAIN RESULTS AND THE ROLE OF CHANCE: There were no differences in background characteristics between the study groups. In the progesterone supplemented group, 83 of 243 patients (34.2%) had a live birth, compared to 59 of 245 patients (24.1%) in the control group (odds ratio 1.635, 95% CI 1.102-2.428, P = 0.017*). The number of pregnancies was 104 of 243 (42.8%) and 83 of 245 (33.9%), respectively (odds ratio 1.465, 95% CI 1.012-2.108, P = 0.049*) and the number of clinical pregnancies was 91 of 243 (37.4%) and 70 of 245 (28.6%), respectively (odds ratio 1.497, 95% CI 1.024-2.188, P = 0.043*). There were no significant differences in biochemical pregnancy rate or miscarriage rate. There was no correlation between outcome and serum progesterone concentration. LIMITATIONS, REASONS FOR CAUTION: The study was not blinded because placebo tablets were not available. Supplementation started on embryo transfer day, regardless of the age of the embryos, which resulted in a shorter supplementation time for Day 5/6 embryos compared to Day 2/3 embryos. WIDER IMPLICATIONS OF THE FINDINGS: Supplementation with progesterone in natural cycles improved the number of live births after frozen-thawed embryo transfer and should therefore be considered for introduction in clinical routine. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by Uppsala University, the Uppsala-Family Planning Foundation, and Ferring Pharmaceuticals AB, Malmö, Sweden. The authors have no personal conflicting interests to declare. TRIAL REGISTRATION NUMBER: NL4152. TRIAL REGISTRATION DATE: 5 December 2013. DATE OF FIRST PATIENT'S ENROLMENT: 18 February 2013.

Effects of Pueraria mirifica on vaginal artery vascularization in postmenopausal women with genitourinary syndrome of menopause.

OBJECTIVE: To compare the effects of 6% Pueraria mirifica vaginal gel with those of placebo gel on vaginal blood flow, vaginal maturation index (VMI), vaginal health index (VHI), endometrial thickness and genitourinary symptoms in postmenopausal women. STUDY DESIGN: In a randomized, double-blinded, placebo-controlled study (TCTR20200624007), 72 postmenopausal women were randomized into the P. mirifica or the placebo gel group. Both groups were followed up at week 4 and week 12. MAIN OUTCOME MEASURE: Doppler ultrasonography pulsatility index (PI) and resistance index (RI), VMI, VHI, endometrial thickness and genitourinary symptoms were evaluated at baseline, at week 4 and week 12 of treatment. RESULTS: Sixty-three participants completed the study. After 4 and 12 weeks of treatment, PI and RI had significantly decreased in the P. mirifica group compared with the placebo group. At week 12, PI in the P. mirifica group and in the placebo group were 3.03 + 1.09 and 6.88 + 2.16, respectively (p = 0.002). Similar changes were also demonstrated in the resistance indices. The P. mirifica group demonstrated a markedly higher mean VMI at week 12 compared with the placebo group, 55.19 ± 18.53 and 20.29 ± 28.46 (p = 0.012). In addition, all parameters of VHI based on the vaginal physical findings at week 12 in the P. mirifica group were significantly higher than in the placebo group (p < 0.001). CONCLUSION: In this study, 6% P. mirifica vaginal gel for 12 weeks in postmenopausal women with GSM appeared to increase vaginal artery circulation and restore atrophic vaginal tissue. CLINICAL TRIAL REGISTRATION NUMBER: TCTR20200624007.

Effect of Chamomile Vaginal Gel on the Sexual Function in Postmenopausal Women: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Female sexual dysfunction (FSD) is a common complaint among postmenopausal women, which is largely because of the genitourinary syndrome in these women (GSM). AIM: Considering the phytoestrogenic effects of chamomile, the present study was primarily aimed to investigate the effect of chamomile vaginal gel on the sexual function of postmenopausal women. The side effects of these drugs were evaluated as a secondary outcome of the study. METHODS: This randomized double-blind clinical trial and placebo-controlled study was conducted on postmenopausal women with sexual dysfunction (FSFI ≤26.55). To this aim, 96 postmenopausal women were randomly assigned into three groups (n = 32 each) including women receiving (i) chamomile vaginal gel 5%, (ii) conjugated estrogen vaginal cream, and (iii) placebo vaginal gel, for 12 weeks (ie, every night in the first 2 weeks, and 2 nights per week in the next 10 weeks, each night 1 g was used). The sexual function was measured using female sexual function index (FSFI) before and after the intervention. Data analysis was performed by chi-square, one-way ANOVA, descriptive statistics, analysis of covariance (ANCOVA), and paired t test using SPSS software version 22. P < .05 was considered statistically significant. OUTCOMES: The main study outcome measure was evaluate the effects of vaginal administration of chamomile gel in comparison with conjugated estrogen cream and placebo gel on postmenopausal FSD using the FSFI. RESULTS: The findings showed that chamomile vaginal gel in compared to placebo vaginal gel caused a significant improvement in all six sexual function domains and the total FSFI score (effect size = +2.9 [95% CI, +2.1 to +3.6], P < .001). Also, there was no significant difference between the chamomile vaginal gel and conjugated estrogen vaginal cream groups in terms of the total score and all sub-domains of sexual function with the exception of orgasm (effect size = +0.13 [95% CI, -0.36 to +0.63], P = .02) and sexual satisfaction (effect size = 0 [95% CI, -0.49 to +0.49], P = .04). Two women in the chamomile group and one in the placebo group experienced a burning sensation (P = .345). CLINICAL IMPLICATIONS: This treatment can be considered as a treatment option for postmenopausal women with sexual dysfunction who have contraindications to the use of hormone therapy. STRENGTHS & LIMITATIONS: This study is the first study to investigate the effectiveness of chamomile vaginal gel on sexual function in postmenopausal women. However, in this study, treatment duration was 12 weeks and no follow up was performed beyond this time CONCLUSION: Based on the results of this study, the use of vaginal chamomile gel improved sexual function in postmenopausal women. Bosak Z, Iravani M, Moghimipour E, et al. Effect of Chamomile Vaginal Gel on the Sexual Function in Postmenopausal Women: A Double-Blind Randomized Controlled Trial. J Sex Med 2022;19:983-994.

Real-world effectiveness and tolerability of Zelesse cream® for treating vulvovaginitis in adult women: an observational, prospective study.

OBJECTIVE: To assess the efficacy, acceptability, and tolerability of a vaginal cream based on plant extracts for treating signs and symptoms of vulvovaginitis (VV) (Zelesse cream®), either as monotherapy (non-infectious VV) or adjuvant to antimicrobial therapy (infectious VV). METHODS: This prospective, observational, multicenter study included women who attended outpatient offices for VV. The severity of signs (vaginal discharge, erythema, and edema) and symptoms (pruritus, burning, and dysuria) was assessed before and after 15±5 days of daily treatment with Zelesse cream on a 4-point scale (18-point global score). RESULTS: The study included 58 women aged 43.0±13.2 years, including 42 who were treated with Zelesse cream only and 16 who used Zelesse cream as adjuvant to antimicrobial therapy. All participants showed significantly reduced scores and absolute prevalence of individual signs and symptoms in both groups. Similarly, the median signs/symptoms decreased by 4.0 and 8.0 points in women using Zelesse only and those using Zelesse plus antimicrobial therapy, respectively. This product was well tolerated and had high acceptability. CONCLUSIONS: Zelesse cream relieves signs and symptoms of VV, either as monotherapy in non-infectious VV or as adjuvant to antimicrobial therapy in infectious VV. Future randomized, placebo-controlled trials with larger sample sizes are warranted.

Efficacy and safety of a new vaginal gel for the treatment of symptoms associated with vulvovaginal atrophy in postmenopausal women: A double-blind randomized placebo-controlled study.

OBJECTIVE: The aim of the present randomized placebo-controlled single-center study was to assess the efficacy and safety of a new vaginal gel (Meclon Idra - Alfasigma) in the treatment of vulvovaginal atrophy (VVA). The gel is composed of sea buckthorn (Hippophaë rhamnoides) oil, aloe vera, 18ß-glycyrrhetic acid, hyaluronic acid and glycogen. The study assessed whether the gel can reduce VVA symptoms (vaginal dryness, itching, burning sensation) and improve sexual function in postmenopausal women over 12 weeks. STUDY DESIGN: Postmenopausal women (n° = 60) reporting VVA symptoms were recruited and randomized in a 1:1 ratio to the gel or placebo. Active vaginal gel or placebo was applied for 14 days and then twice a week for 90 consecutive days. MAIN OUTCOME MEASURE: The Vaginal Health Index (VHI), including vaginal pH, was used to assess changes in objective signs, whereas the self-reported Female Sexual Function Index (FSFI) was used to investigate sexual function. RESULTS: Meclon Idra was effective in reducing vaginal pain, dyspareunia and vaginal pH, with the VHI showing significant improvement at day 90 (P < .0001), and in reducing each VVA symptom (vaginal dryness, vaginal itching, burning sensation) at weeks 2 and 4, and the end of the study (P < .0001). The analysis of FSFI scores showed, after the end of treatment, an improvement of sexual function in the active-treatment group, with a statistically significant increase (P < 0.001) in all domains scores and total score (P < 0.001). CONCLUSIONS: The present single-center randomized clinical trial demonstrated the efficacy, tolerability and safety of 12-week treatment with a new vaginal gel in postmenopausal women with symptoms associated with VVA. Based on this trial, the gel seems to be a valid choice as a single, local agent for relieving VVA symptoms and improving sexual function, and to have good compliance. This trial is registered prospectively with the Clinical Trials Registry - India, number CTRI/2019/05/01911.

Comparison of the effectiveness of Satureja khuzestanica and clotrimazole vaginal creams for the treatment of vulvovaginal candidiasis.

Candidal vaginitis has a relatively high prevalence, and its resistance to treatment is on the rise. Considering the complications of chemical drugs, the use of herbal medicines has now been favored due to the lack of changes in the normal vaginal flora. The aim of this study was to compare the effectiveness of Satureja khuzestanica and clotrimazole vaginal creams for the treatment of candidal vulvovaginitis. A randomized clinical trial was conducted on 84 reproductive-aged women in the city of Ahvaz, Iran. Individuals were randomly divided into two treatment groups: 1% Satureja khuzestanica vaginal creams (n=42) and 1% clotrimazole vaginal cream (n=42) who used a one-full applicator daily for one week. About 4-7 days after the end of treatment, a clinical examination and laboratory re-tests were performed to determine the level of treatment. The data were analyzed using the Mann-Whitney U, t-test and Chi-square tests, with SPSS version 22. After the treatment, no significant difference was observed between the two groups in terms of vaginal discharge (p = 0.32), vaginal itching (p = 0.26), dysuria (p = 0.99) and dyspareunia (p = 0.60). Moreover, the results of culture (p = 0.62) and smear (p = 0.58) were not statistically significant in the two groups. Also, there was no significant difference between the two groups in terms of complete recovery after the treatment (p = 0.35). Satureja khuzestanica seems to have the same effect as clotrimazole in improving the symptoms of vaginal candidiasis, the negative results of culture and smear, as well as complete treatment.

Vaginal tablets of dequalinium chloride 10 mg versus clotrimazole 100 mg for vaginal candidiasis: a double-blind, randomized study.

PURPOSE: To compare the clinical response, microscopic examination and fungal culture between dequalinium chloride (DQC) and clotrimazole (CT) for treating vaginal candidiasis (VC). METHODS: The double-blind, randomized study was conducted from September 2014 to September 2016 at Siriraj Hospital, Thailand. Eligible participants were Thai women diagnosed with VC by microscopic examination. The exclusion criteria included immunocompromised conditions, consumption of antifungal drugs, and having recurrent VC. Each participant was randomized with a 1:1 allocation to receive six vaginal tablets of 100 mg CT or 10 mg DQC. Two visits included 10 ± 2 days (C1) and 38 ± 4 days (C2). Outcome measures were improvement of VC symptoms, microscopic examination, culture, satisfaction and tolerability. RESULTS: Of 155 eligible participants, 150 were randomized and allocated into CT (N = 76) and DQC (N = 74). The average age was 31.1 ± 7.2 years. Comparable improvement of clinical response was demonstrated (OR at C1 0.79, 95% CI 0.56-1.10, p = 0.197; and OR at C2 0.99, 95% CI 0.69-1.43, p = 0.985). Of CT and DQC groups, the microscopic examination was positive at 11/75 (14.9%) vs 18/72 (25.3%) at C1 and 18/74 (24.3%) vs 28/66 (42.4%) at C2. And the culture was positive at 25/75 (33.8%) vs 46/72 (65.7%) at C1 and at 26/74 (36.6%) vs 46/66 (69.7%) at C2. Most participants had high satisfaction and tolerability and none reported any side effects. CONCLUSION: DQC and CT show comparable clinical response but CT results in greater improvement of microscopic examination and fungal culture. CLINICAL TRIAL REGISTRATION: The Clinical Trial Registry number was NCT02242695. (September 17, 2014).

Aloe Vera; A new treatment for atrophic vaginitis, A randomized double-blinded controlled trial.

AIM OF THE STUDY: Vaginal atrophy is of the most common problems during menopause with significant psychosocial and medical consequences. Estrogen as an approved therapy for vaginal atrophy can be associated with adverse effects and several contraindications in menopause patients. The aim is to compare the effect of Aloe Vera vaginal cream with commercially available estrogen vaginal cream for management of vaginal atrophy in menopause females. MATERIALS AND METHODS: This is a double-blinded randomized controlled trial on 60menopause female with complaints of vaginal atrophy symptoms. Subjects were randomly allocated in two groups of 30 patients, named as estrogen and Aloe Vera groups. Vaginal health index (VHI), maturity value (MV), vaginal cytologic smear, transvaginal sonography (TVS) and severity of symptoms related to vaginal atrophy were assessed before and after 6-weeks of vaginal cream administration. RESULTS: Comparison of MV before and after treatment revealed that superficial cells were significantly increased after administration of both vaginal cream (6.67 VS 54.33 in Aloe Vera group; 4.33 VS 59.67 in estrogen group). In addition, VHI (13.83 vs 20.13 in Aloe Vera group; 13.97 vs 19.93 in estrogen group) and symptoms of vaginal atrophy (3.63 vs 1.10 in Aloe Vera group; 3.90 vs 0.66 in estrogen groups) were also significantly improved after treatment in both groups. There was no significant difference between groups after treatment except for fluid volume with a superiority in Aloe Vera group (P-value = 0.004) CONCLUSION: Aloe Vera vaginal cream can be as effective as estrogen vaginal cream in the management of vaginal atrophy in menopause females.

[A multicenter, randomized, open and positive parallel controlled clinical study of clotrimazole vaginal expansion suppository and vaginal tablet in the treatment of mild and moderate vulvovaginal candidiasis].

Objective: Using clotrimazole vaginal tablet as a positive control, to evaluate the results of clotrimazole vaginal expansion suppository in the treatment of mild and moderate vulvovaginal candidiasis in terms of efficacy, patient satisfaction, side effects, and recurrence rate. Methods: This study was jointly conducted by 5 hospitals from August 2017 to October 2018, patients with mild and moderate vulvovaginal candidiasis confirmed by fungal culture and symptoms scores were selected. They were randomized to experimental group and control group as 1∶1 ratio. In the experimental group (n=105), the subjects applied clotrimazole vaginal expansion suppository (150 mg) daily at night for 7 days. In the control group (n=106), the subjects used a single dose of clotrimazole vaginal tablet (500 mg). Follow-ups were performed at (8±3) and (30±5) days after the discontinuation of the drugs, respectively. The difference in clinical symptoms and signs scores was used to evaluate the improvement of clinical symptoms, and the patient's satisfaction and side effects were recorded. Results: At the first follow-up, the experimental group and control group were followed up by fungal culture on the cure rate [66.7% (70/105) versus 63.2% (67/106), P>0.05] and total effective rate [98.1% (103/105) versus 99.1% (105/106), P>0.05], the differences were not statistically significant. At the second follow-up, the recurrence rates of the experimental group and the control group were 5.7% (4/70) and 14.9% (10/67), respectively, with no significant difference (P>0.05). In the evaluation of patient satisfaction, the leakage of the drug in the experimental group was significantly better than that in the control group (P<0.01). The side effects mainly included vaginal stimulation, itching and burning sensation, and there was no statistical difference between the two groups (χ2=1.070, P=0.586). Conclusions: In the treatment of mild and moderate vulvovaginal candidiasis, clotrimazole vaginal expansion suppository is no less effective than clotrimazole vaginal tablet, and there is no significant difference in the recurrence rate between the two. In terms of patient satisfaction, clotrimazole vaginal expansion suppository is superior to clotrimazole vaginal tablet.

Comparison of the effects of Pueraria mirifica gel and of placebo gel on the vaginal microenvironment of postmenopausal women with Genitourinary Syndrome of Menopause (GSM).

OBJECTIVE: To compare the effects of a 12-week course of 5%Pueraria mirifica gel and placebo gel on the prevalence of bacterial vaginosis, vaginal fungi, vaginal pH, vaginal health index (VHI), and genitourinary symptoms in postmenopausal women. STUDY DESIGN: In a randomized, double-blinded, placebo-controlled study (TCTR20160517002), 60 postmenopausal women were randomly assigned to a 12-week course of eitherP. mirifica gel or identical placebo gel. MAIN OUTCOME MEASURE: Vaginal Nugent score, fungal culture, pH, VHI, and genitourinary symptoms were evaluated at baseline and after 12 weeks of treatment. RESULTS: After 12 weeks of treatment, the proportion of participants with an abnormal Nugent score in the P. mirifica and the placebo groups were 6.7 % (2/30) and 23.3 % (7/30), respectively (p =  0.006). The mean changes in Nugent scores and VHI were significantly higher in the P. mirifica group (p <  0.05). There were no significant decreases in the prevalence of symptoms between the two groups after treatment (p > 0.05). CONCLUSION: A 12-week course of treatment with 5 % P. mirifica vaginal gel in postmenopausal women with GSM has been proved to be effective in reducing indicators of bacterial vaginosis compared with placebo gel. Nevertheless, the effect on alleviating genital symptoms was not demonstrated.

The effect of Achillea Millefolium L. on vulvovaginal candidiasis compared with clotrimazole: A randomized controlled trial.

INTRODUCTION: Vulvovaginal candidiasis is the second most common cause of vulvovaginal infections. The aim of this study is to evaluate the effectiveness of vaginal cream of Achillea millefolium extract in women with vulvovaginal candidiasis in comparison with vaginal clotrimazole. MATERIALS AND METHODS: This double-blind randomized clinical trial study was conducted on 80 women diagnosed with vulvovaginal candidiasis clinically and by laboratory test; 40 women received vaginal cream clotrimazole 1 % and 40 received vaginal cream containing the aqueous extract of A. millefolium for 7 days. Clinical and laboratory assessments were performed before and after the intervention. Minimum inhibitory concentration of the extract was evaluated with Broth micro-dilution procedure. RESULTS: The Dermatology life quality index score showed significant reduction in both groups after treatment, but it was significantly more reduced in control group (p < 0.05). Improvement in vulvar erythema was observed in both groups with no statistically difference (p = 0.1). Vaginal culture was negative in term of Candida in 28(77 %) patients of control group and in 18(53 %) patient of experimental group (p < 0.05). The Minimum inhibitory concentration of the extract was 37.5 mg/mL for the standard strain. DISCUSSION AND CONCLUSION: Study results showed that vaginal cream containing A. millefolium could reduce the complaints of vulvovaginal candidiasis. But, future studies with a larger sample size and different dosages are recommended to assess the outcomes of this new treatment.

The effect of Quercus (Oak Gal) vaginal cream versus metronidazole vaginal gel on bacterial vaginosis: A double­blind randomized controlled trial.

OBJECTIVE: This study was aimed to compare the effect of an Oak Gall extract­based cream and a metronidazole Gel on the bacterial vaginosis among women in reproductive age. MATERIAL AND METHODS: This was a double-blind, randomized controlled trial performed on 84 women with BV in reproductive age. Accordingly, the women were randomly assigned to the Oak Gall (n = 42) or metronidazole (n = 42) groups. Diagnosis of BV was confirmed when at least 3 of the 4 Amsel criteria were met by the participants (whitish-grey or thin homogeneous discharge, pH ≥ 4.5, the release of a fishy odor on the addition of 10 % KOH, and detection of clue cells > 20 % in the microscopic examination). For each group, either a methanol extract of Oak Gall vaginal cream or a metronidazole vaginal gel (5 g) was used as intravaginal for 5 consecutive days, and all the signs or symptoms were assessed by passing 4-7 days from the treatment completion. RESULTS: At baseline, the two groups were homogenous in terms of the vaginal burning, odor, dysuria, dyspareunia, and itching. Also, all women in both groups were free of symptoms (vaginal itching and burning sensation, bad odor, dysuria, and dyspareunia) by passing one week from the intervention (p < 0.001). The percent of bacterial vaginosis treatment was in 33(82.1 %) patients in terms of Oak Gall group and in 34(87.5 %) patients of Metronidazole group (p=0.56). Notably, Oak Gall was as effective and safe as metronidazole in the treatment of BV in reproductive-aged women. CONCLUSION: Oak Gall could be recommended for women in reproductive age who are uncomfortable with the potential side effects of synthetic drugs.

Efficacy of a vaginal tablet as a Persian medicine product on vulvovaginal candidiasis: a double-blind, randomised, placebo-controlled trial.

Context: In Persian medicine, topical ingredients such as Rosa damascena Mill. (Rosaceae), are usually recommended for the treatment of uterine diseases. Scientific evaluation of these historical documents can be valuable for finding new potential use in conventional medicine.Objective: This clinical trial was performed to determine whether the use of the 'ward' vaginal tablet, which contains Rosa damascena, Punica granatum L. (Punicaceae), Querqus infectoria Oliv. (Fagaceae), Myrtus communis L. (Myrtaceae) and Nardostachys jatamansi (D.Don) DC. (Caprifoliaceae) could alleviate the symptoms of vulvovaginal candidiasis.Materials and methods: A parallel double-blinded placebo-controlled study was done. Eighteen to fifty-year-old women with vulvovaginal candidiasis were divided into the 'ward' and placebo groups, 46 individuals in each group. The 'ward' group received the 'ward' vaginal tablet containing 200 mg of dried extract. Placebo group received a placebo (composed of corn starch and lactose). One tablet was applied through the vagina for 7 consecutive nights.Results: Two weeks after medication administration, the vaginal discharge sample of patients was re-cultured; 29 patients (63.045%) in the 'ward' group and 6 (13.04%) patients in the placebo group had negative culture (p < 0.001). All clinical symptoms including itching, irritation, and vaginal discharge were significantly reduced in the 'ward' group compared with the placebo group following the intervention and the follow up (p < 0.05).Discussion and conclusions: The findings suggest the 'ward' vaginal tablet could ameliorate vulvovaginal candidiasis. Future larger studies are recommended due to compare the therapeutic effect of the 'ward' vaginal tablet with common treatments.

Comparison of the Effects of Fenugreek Vaginal Cream and Ultra Low- Dose Estrogen on Atrophic Vaginitis.

INTRODUCTION: Atrophic vaginitis is a common problem in postmenopausal women and results from decreased levels of blood estrogen. It is associated with symptoms of itching, burning, dyspareunia, and postmenopausal bleeding. The present study evaluated the effects of fenugreek extract on atrophic vaginitis. MATERIALS AND METHODS: This randomized controlled clinical trial was performed on 60 postmenopausal women in Ardabil, Iran, in 2018. The participants were selected using block randomization with the allocation ratio 1:1. Those in the intervention group received 0.5g (the applicator filled to the half-full mark) fenugreek vaginal cream 5% twice a week for 12 weeks. The control group received conjugated estrogens vaginal cream at the dose of 0.625 mg (the applicator filled to the half-full mark) containing 0.3 mg of conjugated estrogens. Atrophic vaginitis was evaluated before and after the treatment through clinical examination, clinical signs, and measurement of Vaginal Maturation Index (VMI). FINDINGS: After the 12-week intervention and modification of the baseline score, the mean (standard error) score for atrophic vaginitis signs was 3.100 (1.43-4.75). This difference was statistically significant in intragroup comparison and in favor of the control group in intergroup comparison (p=0.001). VMI was less than 49% in 86.7% and 46.7% of the participants in the intervention and control groups, respectively. This was a significant difference in favor of the control group (p=0.001). CONCLUSION: The results of this study showed that total fenugreek extract could be effective in treating signs of atrophic vaginitis, but it was not as effective as ultra-low-dose estrogen.

An Alternative Treatment for Vaginal Cuff Wart: a Case Report.

Human papillomavirus (HPV) has been directly related to acuminate warts and cervical cancer, the second most common neoplasia among women. Given the lack of treatment against the virus itself, many medications have been utilised, mainly aiming in modifying the host's immunological response. We present the case of a 54 years old postmenopausal patient with a history of vaginal cuff wart and HPV persistence that we managed in our clinic for 6 months with a mix of curcumin, aloe vera, amla and other natural ingredients. As the patient was found to be intolerant to imiquimod (one of the most common conservative methods of treatment) we attempted the use of curcumin, which was applied to the area of the wart three times per week for 6 months. Both clinical and colposcopical improvement was noted in regular clinic visits with regression of the lesion. The outcome of this case encourages our view that curcumin should be considered as a significant treatment modality against HPV infection and acuminate warts.

Development and in vivo evaluation of chitosan-gel containing Mitracarpus frigidus methanolic extract for vulvovaginal candidiasis treatment.

Vulvovaginal candidiasis (VVC) is characterized by inflammatory changes in the vaginal mucosa caused by abnormal colonization of Candida species. Traditional topical therapies using reference antifungal drugs usually present several issues and limitations for VVC treatment. Thus, the interest in new vaginal formulations, mainly those based on compounds from natural origin, has been growing over the last years. Methanolic extract from the plant species Mitracarpus frigidus (Willd. Ex Reem Schult.) K. Schum (MFM) has presented potential antifungal activity against C. albicans vaginal infection. Here, we aimed to develop and characterize a gynecological gel formulation based on chitosan containing MFM and to evaluate its anti-C. albicans effectiveness in the treatment of VVC. First, MFM was incorporated into a gel formulation based on chitosan in three final concentrations: 2.5 %, 5.0 %, and 10.0 %. Next, these gel formulations were subjected to stationary and oscillatory rheological tests. Finally, the gel was tested in an experimental VVC model. The rheological tests indicated pseudoplastic fluids, becoming more viscous and elastic with the increase of the extract concentration, indicating intermolecular interactions. Our in vivo analyses demonstrated a great reduction of vulvovaginal fungal burden and infection accompanied with the reduction of mucosal inflammation after MFM chitosan-gel treatment. The present findings open perspectives for the further use of the MFM-chitosan-gel formulation as a therapeutic alternative for VVC treatment.