The Effect of Citrus Aurantium Vaginal Cream on Vaginal Atrophy in Postmenopausal Women: A Quasi-experimental Study.

Background: Vulvovaginal atrophy (VVA) is a common condition and a silent epidemic affecting many postmenopausal women who suffer from it in silence. This study aimed to evaluate the effect of Citrus aurantium vaginal cream on vaginal atrophy in postmenopausal women. Methods: This single-group pretest-posttest quasi-experimental study was conducted on 30 postmenopausal women who were referred to the Gynecology Clinic of Imam Khomeini Hospital in the city of Noor, Iran, from June to November 2020. Citrus aurantium vaginal cream was administered to women diagnosed with vaginal atrophy (based on subjective symptoms of atrophy, descriptive evaluation of the vagina, vaginal pH measurement, and degree of vaginal maturation determined by vaginal smear) every night in the first two weeks and every other night for the second two weeks. Data were collected using the scale of subjective symptoms of vaginal atrophy; descriptive evaluation checklist of vaginal mucosa; laboratory results registration form (vaginal maturation index, vaginal maturation value, and vaginal pH) before the intervention and two and four weeks after the intervention. Data were analyzed using SPSS software (version 24) through the analysis of variance with repeated measurements, and LSD post-hoc test. A P value less than 0.05 (P<0.05) was considered statistically significant. Results: Citrus aurantium vaginal cream improved subjective symptoms of vaginal atrophy (P<0.001), reduced the score of descriptive evaluation of vaginal mucosa (P<0.001), decreased vaginal pH (P<0.001), and increased vaginal maturity (P<0.001). Conclusions: The results showed that citrus aurantium vaginal cream could improve the symptoms of vaginal atrophy without causing serious complications. However, further studies with a control group are suggested to confirm the findings of this study.Trial Registration Number: IRCT20200215046494N.

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.

Development of Dispersible Vaginal Tablets of Tenofovir Loaded Mucoadhesive Chitosan Microparticles for Anti-HIV Pre-Exposure Prophylaxis.

Tenofovir disoproxil fumarate (TDF)-loaded bioadhesive chitosan microparticles (CM) were developed by an emulsification internal gelation technique. Among different batches produced, ECH-4 was found to display a high % entrapment efficiency (68.93 ± 1.76%) and sustained drug release of 88.05 ± 0.38% at 24 h. Solid state characterization of ECH-4 employing DSC and PXRD indicated that the TDF existed in an amorphous state as a solid-solid solution in chitosan. Scanning electron microscopy revealed CM of ECH-4 was spherical in shape with a rough surface topography. Laser scattering analysis using Malvern Master sizer indicated that particle size of ECH-4 was in the range of 0.52 ± 0.10 µm to 284.79 ± 21.42 µm with a surface-mean diameter of 12.41 ± 0.06 µm. Ex vivo mucoadhesion studies using rabbit mucosa as a substrate indicated that 10.34 ± 2.08% of CM of ECH-4 was retained at the end of 24 h. The microparticles of ECH-4 were incorporated into dispersible tablets (DT-TCM) intended for intravaginal administration, in view to arrest the pre-exposure transmission of HIV during sexual intercourse. In vitro release from the dispersible tablet (F3) into simulated vaginal fluid (pH 4.5) displayed a sustained release profile of TDF as 89.98 ± 1.61% of TDF was released at 24 h. The in vitro dissolution profile of the DT-TCM was found to be similar to that of TDF loaded CM with the values of f1 (difference factor) and f2 (similarity factor) being 1.52 and 78.02, respectively. Therefore, DT-TCM would be a promising novel drug delivery platform for pre-exposure prophylaxis against HIV.

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.

Acceptability of Single-dose Clindamycin Gel for Bacterial Vaginosis: A Randomized Controlled Trial.

PURPOSE: The goal of this study was to assess the acceptability of a single-dose bioadhesive 2% clindamycin vaginal gel for bacterial vaginosis (BV). METHODS: This double-blind, placebo-controlled, randomized study compared a new clindamycin gel with placebo gel (2:1 ratio). The primary objective was efficacy; secondary objectives were safety and acceptability. Subjects were evaluated at screening, days 7 to 14 (Day 7-14), and days 21 to 30 (test-of-cure [TOC]). An acceptability questionnaire with 9 questions was administered at the Day 7-14 visit, and a subset of questions (#7-#9) was asked again at the TOC visit. At Visit 1, subjects were provided with a daily electronic diary (e-Diary) to collect information regarding study drug administration, vaginal discharge, odor, itching, and any other treatments used. Study site staff reviewed e-Diaries at the Day 7-14 and TOC visits. FINDINGS: A total of 307 women with BV were randomized to treatment (204 to the clindamycin gel group and 103 to the placebo gel group). Most (88.3%) reported at least one previously diagnosed BV episode, and more than one half (55.4%) had experience with other vaginal treatments for BV. At the TOC visit, almost all (91.1%) of the clindamycin gel subjects described their overall experience with the study drug as "satisfied" or "very satisfied," 95.8% indicated that they would be "likely" or "very likely" to use the product again if it became available after the study and they had BV again, and 93.7% would be "likely" or "very likely" to recommend their treatment to a friend who had BV. Almost all (90.2%) clindamycin-treated subjects responded that application was "clean" or "fairly clean," as opposed to "neither clean nor messy," "fairly messy," or "messy." Although 55.4% experienced leakage in the days after application, only 26.9% of those indicated that it was bothersome. Subjects receiving clindamycin gel also reported improvement in both odor and discharge, commencing shortly after dosing and continuing through the assessment period, regardless of whether they met the critical cure criteria. IMPLICATIONS: A single dose of a new bioadhesive 2% clindamycin vaginal gel showed rapid resolution of symptoms and was highly acceptable as a treatment for bacterial vaginosis. CLINICALTRIALS: gov identifier: NCT04370548.

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.

Prevention of recurrence of bacterial vaginosis using lactobacilli-containing vaginal tablets among women with HIV: a randomized, placebo-controlled, double-blinded phase IV trial.

OBJECTIVES: The effectiveness of lactobacilli-containing vaginal tablets (VT) in bacterial vaginosis (BV) recurrence prevention among women infected with HIV treated with standard oral metronidazole in Pune, India was studied. METHODS: Women infected with HIV with confirmed BV diagnosis (Nugent score ≥7 and Amsel criteria >3) were enrolled in a 12-month, double-blind, randomized, placebo-controlled, phase IV study between 2018 and 2021. After a standard course of oral metronidazole for 7 days (400 mg three times a day), women were randomly assigned to either lactobacilli-containing or placebo VT arms to receive VTs for 4 months. BV recurrence was assessed after the initial cure from BV. RESULTS: Of the 464 women infected with HIV, 80 women with confirmed BV were enrolled. The retention was affected due to the COVID-19 pandemic (6-month retention rates 78%). The cure was seen in 85% and 93.5% of participants from the treatment and placebo arms, respectively, after four VT cycles. BV recurrence was seen in 41.4% and 44.8% in the treatment and placebo arm, respectively, with no significant difference in the two groups. CONCLUSION: The lactobacilli-containing VT was acceptable and safe; however, the addition of VT over standard oral metronidazole did not show any additional benefit in the prevention of BV recurrence in women infected with HIV, indicating the need for long-term randomized trials among them. Registered at Clinical Trials Registry- India, (CTRI) Number: CTRI/2018/04/013298.

The effect of 12 weeks of estriol cream on stress urinary incontinence post-menopause: A prospective multinational observational study.

OBJECTIVE: To quantitate the changes in stress urinary incontinence (SUI) outcome measures after 12 weeks of vaginal estriol cream in women with stress incontinence. METHODS: A prospective multicentre observational study conducted in tertiary urogynaecology centers. Postmenopausal women with pure SUI or stress predominant mixed urinary incontinence (MUI), not receiving any other treatment for their incontinence were given written instructions regarding digital application of a standard dose of vaginal estriol cream. Outcomes were measured at baseline and 12 weeks. The primary objective outcome was vaginal pH. The primary subjective outcome was the stress domain of the Urogenital Distress Inventory-6 (UDI-6). The secondary objective outcome used was the erect cough stress test. Two quality of life questionnaires and two patient reported outcomes were also included. RESULTS: The 46 postmenopausal recruits had a median age of 62.1 interquartile range (IQR 56.2-65.4). At follow up, the primary subjective outcome SUI domain [UDI-6] significantly improved from 83.3 (IQR 50-100) to 33.3 (33.3-66.7, p ≤ 0.001) as did vaginal pH [from 5.1 (4.9-5.9) to 4.9 (4.6-5.0] p ≤ 0.001; 18/43 patients (42%) were dry on cough stress test. CONCLUSIONS: Twelve weeks of vaginal estriol cream significantly reduced symptoms of stress urinary incontinence in this sample of postmenopausal women.

Evaluation of the safety and efficacy of wormwood vaginal gel in improving sexual function and sexual satisfaction in women of reproductive age: A randomized, triple-blinds, placebo-controlled clinical trial.

INTRODUCTION: All aspects of sexual function are related to sexual satisfaction, and not paying attention to sexual problems leads to sexual dissatisfaction. According to studies, sexual satisfaction is a key factor in a couple's quality of life. The aim of this study was to evaluate the safety and efficacy of wormwood vaginal gel in improving sexual function and sexual satisfaction in women of reproductive age. METHODS: This study was a randomized, triple-blinds, parallel-groups clinical trial performed on 76 women of reproductive age (18-45 years) referred to the gynecological clinic of Ghaem Hospital in Mashhad who had sexual dysfunction and low sexual satisfaction. 76 women were assigned to the wormwood gel (n = 38) and placebo (n = 38) groups using random permuted blocks of sizes 4 or 6 and an allocation ratio of 1:1. Wormwood gel or placebo was used for 4 weeks and 3 times a week for 4 weeks from22 May to 23 October 2021. The main data collection tools were the Female Sexual Function Index (FSFI) and Larson Sexual Satisfaction Questionnaire (LSSQ) to access changes in sexual function and sexual satisfaction at baseline and after 4 weeks. RESULTS: The Mean and Standard Deviation of the age of the studied women was 36.8 ± 5.9 years in the intervention group and 37.1 ± 7.3 years in the placebo group. Before the intervention, the Mean and Standard Deviation of the total score of sexual function and sexual satisfaction in the studied women were 17.70 ± 3.66 and 72.20 ± 6.56 in the intervention group and in the placebo group were 18.23 ± 3.84 and 73.26 ± 5.86, respectively. At the end of the intervention, the Mean and Standard Deviation of the total score of female sexual function and sexual satisfaction in the intervention group were 32.11 ± 2.03 and 96.91 ± 7.93 and in the placebo group were 21.07 ± 3.22 and 75.91 ± 8.87, respectively. sexual function and satisfaction improved significantly in the wormwood gel compared to the control group(p < 0.0001). CONCLUSIONS: Based on the findings of this trial, it seems that the wormwood vaginal gel can be used as a topical supplement to improve sexual function and sexual satisfaction in women of reproductive age who have sexual dysfunction and low sexual satisfaction.

Single-Dose, Bioadhesive Clindamycin 2% Gel for Bacterial Vaginosis: A Randomized Controlled Trial.

OBJECTIVE: To assess efficacy and safety of a single-dose vaginal clindamycin gel for bacterial vaginosis treatment. METHODS: We conducted a double-blind, placebo-controlled, randomized study comparing clindamycin gel with placebo (2:1 ratio). Entry required clinical diagnosis of bacterial vaginosis, that is, all four Amsel's criteria, without other genital infections. Nugent scores of 7-10 were required for efficacy assessment, per updated 2019 U.S. Food and Drug Administration guidance. Patients were evaluated at screening, day 7-14, and day 21-30 (test of cure). Clinical cure was defined as resolution of three of four Amsel's criteria. Bacteriologic cure was defined as Nugent score lower than 4. Therapeutic cure was both clinical and bacteriologic cure. Primary outcome was clinical cure at the test-of-cure visit. Secondary endpoints were clinical cure at day 7-14, and bacteriologic and therapeutic cures at day 7-14 and test of cure. A sample size of 188 patients in the clindamycin group compared with 94 patients in the placebo group had 90% power to detect statistically significant difference (P=.05, 2-tailed). RESULTS: Participants were seen between July 9, 2020, and November 12, 2020. Of 307 randomized women, 56.0% were Black and 88.3% reported one or more previous bacterial vaginosis episodes. In the modified intention-to-treat population, 70.5% of patients in the clindamycin group and 35.6% in the placebo group achieved clinical cure at test of cure (primary outcome) (difference of 34.9, 95% CI 19.0-50.8), as did 77.5% of patients in the clindamycin group and 42.6% of patients in the placebo group in the per-protocol population (difference of 34.9, 95% CI 17.0-52.7). Statistically significant differences between groups were seen for all secondary endpoints. Clinical cure rate in patients in the clindamycin group with more than three bacterial vaginosis episodes in the prior year was 70.0%. Approximately 15% (15.3%) of patients in the clindamycin group experienced one or more treatment-emergent adverse events related to study treatment, as did 9.7% of patients in the placebo group. The most frequent treatment-related, treatment-emergent adverse event was vulvovaginal candidiasis. CONCLUSION: A new, single-dose clindamycin vaginal gel was highly effective, with excellent safety, in women disproportionately affected by bacterial vaginosis, with Nugent scores of 7-10 at study entry. FUNDING SOURCE: The study was funded by Daré Bioscience, Inc. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov, NCT04370548.

Vaginal hormone-free moisturising cream is not inferior to an estriol cream for treating symptoms of vulvovaginal atrophy: Prospective, randomised study.

This prospective, open-label, multicentre, multinational, randomised trial investigated the non-inferiority of treatment with a vaginal hormone-free moisturising cream compared to a vaginal estriol (0.1%) cream in a panel of post-menopausal women suffering from symptoms of vulvovaginal dryness in a parallel group design. In total, 172 post-menopausal women were randomly allocated to either one of the two treatments, each administered for 43 days. The primary endpoint was the total severity score of subjective symptoms (dryness, itching, burning and pain unrelated to sexual intercourse) of the respective treatment period. Secondary endpoints were severity of single subjective symptoms (including dyspareunia if sexually active), impairment of daily life, Vaginal Health Index, as well as assessment of safety. In both groups, women treated with hormone-free moisturising cream and those treated with estriol cream, total severity score improved significantly compared to baseline by 5.0 (from 6.1 to 1.1) and by 5.4 (from 6.0 to 0.6), respectively, after 43 days of treatment (p < 0.0001). One-sided test of baseline differences (for a clinically relevant difference Δ = 1.5) confirmed the hormone-free moisturising cream to be non-inferior to the estriol cream. Severity of dyspareunia as well as impairment of daily life due to subjective symptoms, significantly improved for both treatment groups (p<0.0001). Subgroup analysis of women with mild or moderate impairment of daily life at baseline caused by "vaginal dryness" symptoms benefited from both creams, while women with severe impairment showed a significantly greater benefit from the estriol cream (p = 0.0032). Both treatments were well tolerated with no serious adverse events occurring. This study provides clinical evidence that a hormone-free vaginal moisturising cream cannot only improve vaginal dryness compared to an 0.1% estriol cream but also can relieve dyspareunia as well as improve woman's impairment of daily life, justifying its use as a first choice for mild or moderate vulvovaginal dryness symptoms.

Efficacy of interventions to manage sexual dysfunction in women with cancer: a systematic review.

IMPORTANCE: Cancer and its treatment negatively affect female sexual health and function. The prevalence of female sexual dysfunction after cancer is between 33% and 43%. Numerous studies have addressed treatment options for sexual dysfunction in women with cancer, but it still remains a challenge to select the most efficacious option for patients. OBJECTIVE: To compile and appraise recent evidence of any interventions for managing sexual dysfunction in female cancer survivors. EVIDENCE REVIEW: A literature search of the electronic databases MEDLINE, EMBASE, PsycINFO, and Cochrane Central Register of Controlled Trials (January 2011 to February 2021) was conducted using general search terms of "women", "cancer", "intervention", "sexual dysfunction". We included randomized controlled trials (RCTs) and uncontrolled before-after studies that evaluated the efficacy of intervention for female sexual dysfunction in women with history of cancer. Methodological quality of studies was assessed using Risk of Bias (RoB) 2.0 for RCTs and National Institutes of Health (NIH) assessment tools for uncontrolled before-after studies. FINDINGS: Thirty-six studies were included for qualitative synthesis (14 RCTs (n = 1284), 17 uncontrolled trials (n = 589), and 5 cohort studies (n = 497). Only four studies were at low risk of bias. Topical interventions (vaginal gels or creams) were able to alleviate vaginal dryness and dyspareunia, with intravaginal dehydroepiandrosterone (DHEA) (6.5 mg) gel showing evidence of improved sexual function. Evidence for estriol-lactobacilli vaginal tablets was unreliable due to a small-scale study. Psychoeducational therapy (internet-based cognitive behavioral therapy [CBT]) studies typically were at high risk of bias, but all displayed significant improvements of sexual function. Both laser therapy (fractional CO2 and erbium) and multimodal approach studies were at concerning risk of bias, although suggesting beneficial effects on sexual function. CONCLUSIONS AND RELEVANCE: The most reliable evidence for improvement was from a study of DHEA vaginal gel, but in general, gels or creams were useful in reducing dyspareunia. Pharmacological, psychoeducational, laser therapy, and multimodal approaches demonstrated potential in managing cancer-related sexual issues, but most were small in size (10-70 participants), with moderate to high risk of bias. Therefore, large-scale, double-blind, RCTs with long-period follow-up, and at low risk of bias are needed to show efficacy for these interventions.

Video Summary : http://links.lww.com/MENO/A912 .

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.

Polycarbophil vaginal moisturizing gel versus hyaluronic acid gel in women affected by vaginal dryness in late menopausal transition: A prospective randomized trial.

OBJECTIVES: During menopausal transition, women are frequently affected by vulvovaginal atrophy (VVA), due to the decline of estrogen levels. Resulting symptoms are itching, burning, dyspareunia, and vaginal dryness (reported in up to 85%). The aim of this trial was to verify if medical device polycarbophil vaginal (PCV) moisturizer gel is not less effective than hyaluronic acid (HA) gel in treating vaginal dryness. MATERIAL AND METHODS: This was a multicenter, open label, randomized, parallel group, comparative study with non-inferiority design. Female included were ≥45 to ≤55 years in the menopausal transition, with subjective dryness, any objective sign of VVA, pH > 5, and body mass index of ≥18.5 to ≤36 kg/m2. Subjects were randomized to 1 g of PCV gel twice a week for 30 days or 3 g of HA vaginal gel every 3 days for 30 days. RESULTS: 53 subjects (mean age 49.45 ± 2.96 years) were analyzed. Vaginal health index showed an improvement (p < 0.001) in both groups (from 12.54 ± 1.37 to 16.36 ± 2.66 for PCV, from 12.00 ± 1.91 to 16.60 ± 2.50 for HA), but the difference between final means (95%CI: -1.66 to 1.18) evidenced that PCV is non-inferior to HA treatment. Similarly, an improvement was evidenced in vaginal maturation index (p = 0.005 for PCV, ns. for HA), female sexual function index (p < 0.001 for PCV, p < 0.001 for HA), and SF-12 (p < 0.001 for PCV, p < 0.001 for HA), with no difference between groups. Safety was optimal and no adverse events were reported. CONCLUSIONS: The use of HA gel does not give additional benefits to those that are already provided by the moisturizing PCV.

The effect of intra-vaginal oxytocin on sexual function in breastfeeding mothers: a randomized triple-blind placebo-controlled trial.

BACKGROUND: Considering the importance of sexual function, high prevalence of sexual dysfunction (especially dyspareunia caused by atrophic vaginitis) in breastfeeding women, and lack of effective interventions, the present research aimed to determine the effect of oxytocin (OXT) vaginal gel on sexual function (primary outcome), sexual satisfaction, and depression (secondary outcomes) in the breastfeeding women. METHODS: This randomized triple-blind controlled trial was conducted on 64 breastfeeding women who referred to health centers in the city of Tabriz, Iran, in 2020-21. Participants were equally assigned to intervention/control groups using block randomization. 200 IU of OXT vaginal gel was given to the participants in the intervention group daily for eight week and the same protocol was carried out for the control group with placebo. Standard questionnaires of Female Sexual Function Index (FSFI), Edinburgh Postpartum Depression Scale (EPDS) and Sexual satisfaction scale for women (SSSW) were completed at baseline and 8 weeks after intervention. ANCOVA test was used to compare post-intervention mean score of the groups, adjusted for the baseline values. RESULTS: After intervention, there was no statistically significant difference between groups in terms of mean total score of FSFI (Adjusted Mean Difference (AMD): 1.14; 95% Confidence Interval (95% CI): -1.28 to 9.16; P= 0.349) and sexual satisfaction (AMD: 5.01; 95% CI: -0.53 to 10.56; P= 0.075). However, there was statistically significant difference between the groups in terms of mean scores of sexual contentment (AMD: 1.56; 95% CI: 0.29 to 2.83; P = 0.017) and depression (AMD: -1.90; 95% CI: -1.27 to -2.54; P < 0.001). One participant in the OXT group and one participant in the placebo group reported mild uterine contraction and one person in the placebo group reported vaginal burning sensations. CONCLUSIONS: No evidence was found for the effects of OXT gel in the improvement of FSFI, even though, OXT significantly improved sexual satisfaction in the domain of contentment, and improved the symptoms of depression in comparison to the placebo group. However, a definite conclusion requires more research in this regard. TRIAL REGISTRATION: the Iranian Registry of Clinical Trials (IRCT), code: IRCT20120718010324N55 , Date of registration: 27/05/2020, URL: https://en.irct.ir/user/trial/44986/view .

Efficacy and safety of prolonged-release hyaluronic acid derivative vaginal application in the postpartum period: a prospective randomised clinical trial.

INTRODUCTION: In puerperium, the hypoestrogenic state induced by delivery and subsequently sustained by lactation may lead to vaginal dryness, burning, and itching sensation, contributing to the onset of sexual dysfunction. MATERIAL AND METHODS: This was a prospective, randomized, controlled, open-label study (NCT04560283) for evaluating the effects of application of a prolonged-release hyaluronic acid derivative vaginal gel in restoring sexual function during the postpartum period. Eighty-five patients were randomized to apply prolonged-release Hydeal-D 0.2% vaginal gel (Fidia Farmaceutici, Abano Terme, Italy; n = 43) every three days for 12 consecutive weeks or expectant management (n = 42). RESULTS: Women undergoing treatment had a more elevate increase in Female Sexual Function Index (FSFI) total score (+15.1 ± 11.9 vs +6.5 ± 8.9, p < 0.001) and a higher decrease in vaginal pH (-1.2 ± 0.7 vs -0.2 ± 1.1; p < 0.001). Moreover, the proportion of vaginal smears with maturation index (VMI) >65 was significantly higher in patients treated (80.6% vs 35.3%; p = 0.004). Edinburgh Postnatal Depression Scale (EPDS) decreased significantly in both groups with no inter-group difference (p = 0.459). Only two cases (4.8%) of moderate vaginal burning sensation were reported in patients undergoing local vaginal therapy. CONCLUSIONS: The results of our study demonstrated that hyaluronic acid derivative vaginal gel (Hydeal-D) was able to improve sexual function of puerperal women in the short-term treatment.KEY MESSAGEIn the puerperium, the hypoestrogenic state induced by delivery and subsequently sustained by lactation may lead to vaginal dryness, burning, and itching sensation, contributing to the onset of sexual dysfunction.Hydeal-D is a prolonged-release hyaluronic acid derivative characterised by elevated resistance to enzymatic breakdown. During puerperium, its local application may improve the vaginal microenvironment by ensuring a better migration and proliferation of cells involved in local tissue repair.Among puerperal women, Hydeal-D vaginal gel causes a significant improvement of sexual function, including desire, arousal, and lubrification, compared to expectant management. Furthermore, it leads to a decrease in vaginal pH and an increase of the trophic status of vaginal epithelium.

Pharmacokinetics of vaginally applied integrase inhibitors in macaques.

OBJECTIVES: We conducted a detailed pharmacokinetic assessment in macaques treated with vaginal gels formulated with HIV integrase strand transfer inhibitors (INSTIs) to better understand drug distribution and identify INSTI concentrations associated with previously demonstrated in vivo protection against vaginal simian HIV challenge. METHODS: Six macaques received vaginal gel containing 1% raltegravir (30 mg) once-weekly over 6 weeks. Following a washout period, five macaques received once-weekly gel containing 0.23% L-870,812 (7 mg). Drug concentrations were measured in plasma, mucosal fluids and vaginal tissues at baseline and 2, 5 and 24 h post-dosing. RESULTS: The median maximum concentration (Cmax) for raltegravir and L-870,812 in plasma was below the limit of quantification and 41.1 ng/mL, respectively. The Cmax in vaginal fluids (1441 and 1250 µg/mL) and tissues (266.7 and 368.4 µg/g) was achieved 2-5 h after dosing, respectively. A similar half-life was observed for raltegravir and L-870,812 in vaginal fluids (8-10 h) and remained 3-4 orders of magnitude above the protein-adjusted IC95 (0.016 and 0.106 µg/mL, respectively) at 24 h. Drug concentrations in vaginal fluids correlated well with those in vaginal tissues (Pearson r ≥ 0.788). Both drugs were consistently detected in rectal fluids 2 h after vaginal dosing, albeit at much lower levels (31-92-fold) than those in vaginal fluids. CONCLUSIONS: To the best of our knowledge, this study provides the first data on INSTI levels in vaginal tissues associated with in vivo protection and demonstrates rectal drug distribution of INSTIs after vaginal dosing. These findings may inform dose selection for topical products with INSTIs for HIV prevention.

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.

Bioadhesive-Thermosensitive In Situ Vaginal Gel of the Gel Flake-Solid Dispersion of Itraconazole for Enhanced Antifungal Activity in the Treatment of Vaginal Candidiasis.

The poor solubility of itraconazole (ITZ) has limited its efficacy in the treatment of vaginal candidiasis. Accordingly, the improvement of ITZ solubility using a solid dispersion technique was important to enhance its antifungal activity. Besides, as the purpose of this research was to develop local-targeting formulations, bioadhesive-thermosensitive in situ vaginal gel combined with the gel-flake system was found to be the most suitable choice. To obtain optimum solubility, entrapment efficiency, and drug-loading capacity, optimization of solid dispersion (SD) and gel-flake formulations of ITZ was performed using a composite central design. The results showed that the optimized formulation of SD-ITZ was able to significantly enhance its solubility in both water and simulated vaginal fluid to reach the values of 4.211 ± 0.23 and 4.291 ± 0.21 mg/mL, respectively. Additionally, the optimized formulation of SD-ITZ gel flakes possessed desirable entrapment efficiency and drug-loading capacity. The in situ vaginal gel containing SD-ITZ gel flakes was prepared using PF-127 and PF-68, as the gelling agents, with the addition of hydroxypropyl methylcellulose (HPMC) as the mucoadhesive polymer. It was found that the obtained in situ vaginal gel provided desirable physicochemical properties and was able to retain an amount of more than 4 mg of ITZ in the vaginal tissue after 8 h. Importantly, according to the in vivo antifungal activity using infection animal models, the incorporation of the solid dispersion technique and gel-flake system in the formulation of the bioadhesive-thermosensitive in situ vaginal gel led to the most significant decrease of the growth of Candida albicans reaching <1 log colony-forming units (CFU)/mL or equivalent to <10% of the total colony after 14 days, indicating the improvement of ITZ antifungal activity compared to other treated groups. Therefore, these studies confirmed a great potential to enhance the efficacy of ITZ in treating vaginal candidiasis. Following these findings, several further experiments need to be performed to ensure acceptability and usability before the research reaches the clinical stage.