Vaginal Gel Research Articles

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

To assess efficacy and safety of a single-dose vaginal clindamycin gel for bacterial vaginosis treatment. 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). 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. 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. The study was funded by Daré Bioscience, Inc. ClinicalTrials.gov, NCT04370548.

A Prebiotic Hydrogel to Prevent Cervical Cancer by Optimizing the Vaginal Ecology and Reducing Oncogenic Biological Risk Factors in Women Across Global Health Care Access

PURPOSE Persistent oncogenic, high-risk human papillomavirus (hrHPV) is a leading cause of cervical cancer and driven by vaginal dysbiosis and mucosal irritation. There is a high need for a product to optimize vaginal ecology and decrease biological risk factors of hrHPV persistence and cervical cancer. METHODS A prebiotic hydrogel (PreBioGyn) was designed for cervical cancer prevention to support the cervicovaginal ecology and anti-viral function. PreBioGyn was compared to over-the-counter (OTC) acidifying vaginal gels RepHresh and Trimosan for impact on: (1) in-vitro growth of L. crispatus—a Lactobacillus essential for the healthy vaginal biome; (2) inhibition of P. bivia—a pathobiont characteristic of vaginal dysbiosis and directly linked to hrHPV reactivation and cervical cancer spread; (3) mucosal irritation potential measured as daily mucus production by slugs (Arion lusitanicus) after 5-day intermittent product exposure; and (4) osmolality and mucoadhesion essential for compatibility with the cervicovaginal mucosal barrier (ability of gel to interdigitate with mucins in vivo). RESULTS Exposure to PreBioGyn for 24 hours completely suppressed P. bivia while sustaining L. crispatus growth which was recovered at 100 ± 1%. Trimosan was bactericidal to L. crispatus within 4 hours incubation and RepHresh within 24 hours of incubation. The mucosal irritation potential of PreBioGyn equaled negative controls, whereas the OTC acidifying-gels resulted in greater irritation potential with > 2-fold mucus production versus the control ( P < .05). The PreBioGyn formula was iso-osmotic to the human vagina (280 mOsmo/kg), while RepHresh was hyper- (1,400 mOsmo/kg) and Trimosan - hypoosmotic (81 mOsmo/kg). The mucoadhesion index of PreBioGyn (10 ± 2.0) was higher ( P < .05) than that of RepHresh (1 ± 0.2) and Trimosan (1 ± 0.3). CONCLUSION Our results provide preclinical evidence for the biocompatibility and safety of the Pre-BioGyn gel. The prebiotic PreBioGyn vaginal gel improved microbiota parameters essential for cervical cancer prevention, compared to leading OTC acidifying-gels. PreBioGyn may offer a simple, affordable user-directed cervical cancer prevention intervention.

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

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. To compile and appraise recent evidence of any interventions for managing sexual dysfunction in female cancer survivors. 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. 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. 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.

Hyaluronic acid in gynecology and obstetrics

Introduction: Hyaluronic acid (HA) is a polysaccharide classified in the group of glycosaminoglycans. Naturally it occurs in the dermis and is responsible for the elasticity of the skin. In medicine, it can be found cross-linked, partially cross-linked or non-cross-linked, which is associated with different densities and the ability to bind water molecules. It (HA) is used in many areas, including ophthalmology, rheumatology, and dermatology. There are many studies and reports, that it can be used in gynecology and obstetrics in various diseases.Material and methods: The PubMed scientific base was reviewed in 2015-2022 using the keywords hyaluronic acid, gynecology, obstetrics.Results: Intrauterine adhesions are a complication of various procedures performed in the uterine cavity, from curettage to removal of the septum or uterine fibroids. Numerous studies suggest, that hyaluronic acid may be an effective agent in preventing formation of adhesions. For menopausal women, it may relieve symptoms associated with vaginal atrophy. Indocyanine green is used for intraoperative visualization of neoplastic tissues and used in case of cervical cancer. There are reports, that stating hyaluronic acid can increase stability of this substance, which can improve imaging. In the case of hyaluronic acid in the form of vaginal gel, a beneficial effect on hydration and sexual function of women both after childbirth and after menopause was noticed. There are reports of its use in prevention of ovarian failure after chemotherapy and its positive aspects in assisted reproductive techniques.Conclusions: Hyaluronic acid can be used in many gynecological and obstetric diseases, positively influencing the life of women in both fertility and sexual areas and also in the group of cancer patients. Therefore, further large, randomized, multicentre studies confirming action of this substance, determining its dose, method and schedule of administration are important.

Sexual Satisfaction Results With the Vaginal pH Modulator From the Phase 3 AMPOWER Study

The novel vaginal pH modulator (VPM; Phexxi) is a non-hormonal, woman-controlled, on-demand, water-based, surfactant-free contraceptive vaginal gel; VPM has also been cleared by the Food and Drug Administration for use as a personal lubricant. The aim of this study is to report on sexual satisfaction results from the phase 3 AMPOWER study. AMPOWER was a single-arm, open-label, multicenter study to assess the safety and efficacy of VPM in preventing pregnancy. Women were enrolled who were healthy, age 18-35 years, and sexually active with regular cyclic menses. Women's satisfaction (including sexual satisfaction) was an exploratory endpoint measured at Baseline and Visits 3-5; sexual satisfaction-related patient reported outcomes (PROs) were assessed via 3 different questions: (i) a question related to the impact on a woman's sex life; (ii) a question from the Sexual Function Questionnaire (SFQ) related to the frequency of ten sexual problems; and (iii) a question from the Female Sexual Function Index (FSFI) related to lubrication. For sexual satisfaction-related PRO measures with baseline assessments, the majority of women reported the same or improved scores at Visit 5 (ranging from 85.8% to 98.4%). The percentage of women who reported that their sex life was improved and/or maintained was higher in Visit 3, 4, and 5 (95.4%, 95.1%, and 93.6%, respectively) compared to Baseline (87.6%). The mean impact on sex life score significantly improved at Visit 5 compared to Baseline (P < .001). In the SFQ, the mean score significantly improved (P < .005) at Visit 5 vs Baseline in 7 of the 10 variables measured (vaginal dryness, lack of sexual interest and/or desire, vaginal tightness, pain, anxiety, unable to orgasm, and vaginal bleeding or irritation). In women who reported sexual activity in the last 4 weeks, the mean FSFI score also significantly improved from Baseline to Visit 5 (P = .037). In this post-hoc analysis of the phase 3 AMPOWER study, the PRO results demonstrate a high level of sexual satisfaction with VPM. The primary strength of this analysis was the large study size of 1,330 women. Limitations included the non-randomized study design, the post-hoc nature of the analysis, and the fact that sexual satisfaction was an exploratory endpoint. As a non-hormonal, woman-controlled, on-demand, lubricating contraceptive gel, VPM offers women a unique set of benefits with positive impacts on their sexual health.

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

Female sexual dysfunction (FSD) is a common complaint among postmenopausal women, which is largely because of the genitourinary syndrome in these women (GSM). 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. 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. 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. 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). This treatment can be considered as a treatment option for postmenopausal women with sexual dysfunction who have contraindications to the use of hormone therapy. 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. Based on the results of this study, the use of vaginal chamomile gel improved sexual function in postmenopausal women.

A Critical Review on Thermo-Sensitive Vaginal Gel for the Foundation of Preparing Thermo-Sensitive Vaginal Gel of PVK (Panchvalkal Kashaya) Extract

RTI (Reproductive Tract Infection) is the vital cause of suffering in women and neonates. According to WHO estimation 340 million new cases of curable STI (Sexually Transmitted Disease) other than HIV/AIDS occurs every year, most of which are occurring in developing countries. Genital tract infection is the prime cause of most gynaecological disease. Vaginal candidiasis is the most common cause of Genital tract infection. It (Vaginal candidiasis) is a common condition and up to 75% of all women suffer at least one episode of this infection during their life time. For treating the pathological condition of genital tract, direct application or self application of medicine is very difficult and the residence time of the medicine is less due to self cleansing properties of vaginal canal. Application of the drug in other route may cause systemic adverse reaction. To overcome this arduous situation, in situ thermo-sensitive gel form has great importance. In this article an attempt have been made for the review of the thermo-sensitive vaginal gel and the scholar has gathered the basic knowledge to develop an Ayurvedic formulation Panchavalkal kashaya thermo-sensitive vaginal gel by this review. This work will be done in School of Pharmaceutical Science, Shoolini University, Solan, HP.

Long-acting injections for HIV prevention among women in sub-Saharan Africa

Women in sub-Saharan Africa are one of the groups at highest risk of HIV in the world, encompassing 38% of new cases globally.1 Multiple HIV prevention modalities have been developed and trialled in women in sub-Saharan Africa with limited success. Tenofovir vaginal gels showed initial promise with a 39% overall reduction in HIV infection,2 but later trials showed no evidence of protection.3 Two clinical trials of dapivirine vaginal rings showed an overall 27–31% risk reduction.4,5 Daily oral pills containing tenofovir disoproxil fumarate are currently the standard for pre-exposure prophylaxis (PrEP).

Vaginal Dysbiosis Management and the Efficacy of a Non-Hormonal Hyaluronic Acid-Based Vaginal Gel (Palomacare®) as an Adjuvant Treatment: The Palomascopia Survey

Vaginal Dysbiosis Management and the Efficacy of a Non-Hormonal Hyaluronic Acid-Based Vaginal Gel (Palomacare®) as an Adjuvant Treatment: The Palomascopia Survey

Frequency of Severe Postpartum Hemorrhage After Delivery Among Obese Pregnant Women

Objective: To determine the frequency of severe postpartum hemorrhage after delivery among obese pregnant women. Methods: This case series was carried out from 15th December 2015 to 15th October 2016 at Department of Obstetrics &amp; Gynaecology, Nishtar Hospital, Multan. A total of 505 obese pregnant women with gestational age 38–41 weeks and parity ≤ 3 undergone vaginal delivery or elective cesarean section were included. Women with history of hypertension, diabetes, renal disease and pre-eclampsia were excluded. In vaginal delivery women were given prostaglandin E2 vaginal gel 1 gm and the same dose repeated at six hourly intervals for maximum three doses under supervision of consultant. In patients undergone elective caesarean section, caesarean section was done by consultant gynecologist. After delivery, data was collected for severe postpartum hemorrhage. Results: Age range in this study was 25 to 35 years with mean age of 30.318 ± 2.71 years. Mean gestational age was 39.429 ±1.11 weeks and mean BMI was 28.289± 1.06 Kg/m2. Majority of the patients were of 25–30 years 268(53.1%). Parity of 2–3 was present in 69.3% women. Cesarean Section rate was 34.3% and vaginal delivery was 65.7%. Severe PPH was seen in 11.1% obese women. Conclusion: Obese women should be regarded as high risk for PPH. Keywords: Obesity, Mode of delivery, Severe postpartum hemorrhage

Management of genitourinary syndrome of menopause in breast cancer survivors: An update.

There is increasing attention about managing the adverse effects of adjuvant therapy (Chemotherapy and anti-estrogen treatment) for breast cancer survivors (BCSs). Vulvovaginal atrophy (VVA), caused by decreased levels of circulating estrogen to urogenital receptors, is commonly experienced by this patients. Women receiving antiestrogen therapy, specifically aromatase inhibitors, often suffer from vaginal dryness, itching, irritation, dyspareunia, and dysuria, collectively known as genitourinary syndrome of menopause (GSM), that it can in turn lead to pain, discomfort, impairment of sexual function and negatively impact on multiple domains of quality of life (QoL). The worsening of QoL in these patients due to GSM symptoms can lead to discontinuation of hormone adjuvant therapies and therefore must be addressed properly. The diagnosis of VVA is confirmed through patient-reported symptoms and gynecological examination of external structures, introitus, and vaginal mucosa. Systemic estrogen treatment is contraindicated in BCSs. In these patients, GSM may be prevented, reduced and managed in most cases but this requires early recognition and appropriate treatment, but it is normally undertreated by oncologists because of fear of cancer recurrence, specifically when considering treatment with vaginal estrogen therapy (VET) because of unknown levels of systemic absorption of estradiol. Lifestyle modifications and nonhormonal treatments (vaginal moisturizers, lubricants, and gels) are the first-line treatment for GSM both in healthy women as BCSs, but when these are not effective for symptom relief, other options can be considered, such as VET, ospemifene, local androgens, intravaginal dehydroepiandrosterone (prasterone), or laser therapy (erbium or CO2 Laser). The present data suggest that these therapies are effective for VVA in BCSs; however, safety remains controversial and a there is a major concern with all of these treatments. We review current evidence for various nonpharmacologic and pharmacologic therapeutic modalities for GSM in BCSs and highlight the substantial gaps in the evidence for safe and effective therapies and the need for future research. We include recommendations for an approach to the management of GSM in women at high risk for breast cancer, women with estrogen-receptor positive breast cancers, women with triple-negative breast cancers, and women with metastatic disease.

Drug Formulations for Localized Treatment of Human Papillomavirus-Induced Lesions

BackgroundThe human papillomavirus (HPV) is responsible for over 90% of all cervical cancer cases. The use of vaginal gels is often indicated for local vaginal drug delivery. Previous studies have shown that Thymus vulgaris essential oil (TEO) exhibits anticancer properties besides antifungal and antibacterial properties. Its activity derives from a specific increase in free radicals and oxidative stress caused in cancer cells. Furthermore, mitoxantrone (MTX), an anthracenedione, and C8, an acridine orange derivative, were shown to inhibit the growth of the cervical cancer cell line HeLa. ResultsThe results showed that TEO + C8 is the most promising formulation in terms of viscosity and osmolality properties in vaginal fluid simulant (VFS). The combined action of TEO with the compounds MTX and C8 resulted in HeLa cell viability reduction compared with the effect obtained with the individual formulations containing each one of the compounds. ConclusionsThe formulation TEO + C8 holds promise in terms of cost-benefit and topical application of the active compound for the HeLa cells.

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

ObjectivesDuring 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 methodsThis 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. Results53 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. ConclusionsThe use of HA gel does not give additional benefits to those that are already provided by the moisturizing PCV.

Systemic and Local Pharmacokinetics of DARE-BV1, a Novel Single Dose 2% Clindamycin Phosphate Vaginal Gel for the Treatment of Bacterial Vaginosis

DARE-BV1 is a novel, highly viscous single dose 2% clindamycin phosphate vaginal gel being investigated as a new treatment for bacterial vaginosis. In a recently completed large, randomized multi-center, placebo-controlled study, DARE-BV1 demonstrated a clinical cure of 70.5% vs. 35.6% in the placebo group (p < 0.001) at Days 21-30. The objective of this study was to determine the systemic and vaginal pharmacokinetics (PK) of DARE-BV1.

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

BackgroundConsidering 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.MethodsThis 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.ResultsAfter 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.ConclusionsNo 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 registrationthe Iranian Registry of Clinical Trials (IRCT), code: IRCT20120718010324N55, Date of registration: 27/05/2020, URL: https://en.irct.ir/user/trial/44986/view.

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

ObjectiveTo 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 designIn 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 measureDoppler 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. ResultsSixty-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). ConclusionIn 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 NumberTCTR20200624007.

Preferences for HIV Preexposure Prophylaxis Products Among Black Women in the U.S.

In a nationwide sample of Black women in the U.S., we assessed preferences for HIV preexposure prophylaxis (PrEP) products, including long-acting injectable (LAI) PrEP and once-daily oral PrEP. Among 315 respondents, 32.1% were aware of PrEP and 40.6% were interested in using it; interest increased to 62.2% if PrEP were provided for free. Oral PrEP was the preferred option (51.1%), followed by LAI PrEP (25.7%), vaginal gel (16.5%), and vaginal ring (6.7%). When examining oral and LAI PrEP alone, most (62.7%) preferred oral PrEP. LAI PrEP was more likely to be preferred among respondents with concerns about healthcare costs or PrEP-related stigma, and among those who reported inconsistent condom use and multiple sexual partners. Although most Black women preferred oral PrEP, LAI PrEP may be appealing to a subset with social and structural barriers to PrEP use, such as cost and stigma, and those at increased risk of HIV infection.

AgNPs reduce reproductive capability of female mouse for their toxic effects on mouse early embryo development.

Silver nanoparticles (AgNPs) are widely applied in the field of personal protection for their powerful toxic effects on cells, and recently, a new type of vaginal gel with AgNPs is used to protect the female reproductive tract from microbes and viruses. However, a high risk of AgNPs to the fetus and the underlying mechanism of AgNPs to interfere in embryo development still remain unclear. Thus, this study investigated the impact of two drugs of vaginal gel with AgNPs on reproductive capability of the female mouse by animal experiment. Then, kinetics of AgNPs affecting embryo development was investigated by in vitro embryos culturing, and cell membrane potential (CMP) of zygotes was analyzed by DiBAC4(3) staining. Results indicated that one of the drugs of vaginal gel certainly injured embryo development in spite of no apparent histological change found in ovaries and uteruses of drug-treated mice. In vitro embryo culturing discovered that the toxic effect of AgNPs on embryo development presented particle sizes and dose dependent, and AgNP treatment could rapidly trigger depolarization of the cell membrane of zygotes. Moreover, AgNPs changed the gene expression pattern of Oct-4 and Cdx2 in blastocysts. All these findings suggest that AgNPs can interfere with normal cellular status including cell membrane potential, which has not been noticed in previous studies on the impact of AgNPs on mammalian embryos. Thus, findings of this study alarm us the risk of applying vaginal gel with AgNPs in individual caring and protection of the female reproductive system.

Early Effect of 0.005% Estriol Vaginal Gel on Symptoms and Signs of Vulvovaginal Atrophy.

ObjectivesThis study aims to assess the effect of ultralow dose 0.005% estriol vaginal gel in women with genitourinary syndrome of menopause (GSM).MethodsIn this prospective and multicenter single-arm study, efficacy was assessed by the evaluation of the epithelial maturation value (MV), vaginal pH, symptoms and signs of vulvovaginal atrophy. Tolerability, acceptability, and the effect on intimate relationships were also evaluated.ResultsWe included 35 postmenopausal women with moderate-to-severe vaginal dryness. The most bothering symptom reported was vaginal dryness. The mean increase in the MV after 7 and 14 days of treatment were 22.1 (P < 0.001) and 39.9 (P < 0.001) points, with an increase in the superficial cells of 17.7 percentage points (pp) (95% confidence interval [CI], 7.9–27.4; P < 0.001) and 41.4 pp (95% CI, 28.2–54.6; P < 0.001) observed at the timepoints. Additionally, the pH decreased by 0.6 ± 0.7 (mean ± SD) at 7 days (P < 0.0001) and by 1.1± 0.8 at 14 days (P < 0.0001) from a baseline mean value of 6.3 ± 0.8. The severity of vaginal dryness (range, 0 [none] to 3 [severe]) was significantly reduced by a mean of 1.4 points (P < 0.0001) at 7 days and 2 points (P < 0.0001) at 14 days.ConclusionsUltralow dose 0.005% estriol vaginal gel produced a rapid improvement of most relevant symptoms and signs of GSM. This clinically meaningful response was observed from the initial days of treatment, confirming a fast onset and a progressive action.

Enzyme Responsive Vaginal Microbicide Gels Containing Maraviroc and Tenofovir Microspheres Designed for Acid Phosphatase-Triggered Release for Pre-Exposure Prophylaxis of HIV-1: A Comparative Analysis of a Bigel and Thermosensitive Gel.

The challenges encountered with conventional microbicide gels has necessitated the quest for alternative options. This study aimed to formulate and evaluate a bigel and thermosensitive gel, designed to combat the challenges of leakage and short-residence time in the vagina. Ionic-gelation technique was used to formulate maraviroc and tenofovir microspheres. The microspheres were incorporated into a thermosensitive gel and bigel, then evaluated. Enzyme degradation assay was used to assess the effect of the acid phosphatase enzyme on the release profile of maraviroc and tenofovir microspheres. HIV efficacy and cytotoxicity of the microspheres were assessed using HIV-1-BaL virus strain and HeLa cell lines, respectively. Maraviroc and tenofovir release kinetics followed zero-order and Higuchi model kinetics. However, under the influence of the enzyme, maraviroc release was governed by first-order model, while tenofovir followed a super case II transport-mechanism. The altered mode of release and drug transport mechanism suggests a triggered release. The assay of the microspheres suspension on the HeLa cells did not show signs of cytotoxicity. The thermosensitive gel and bigel elicited a progressive decline in HIV infectivity, until at concentrations of 1 μg/mL and 0.1 μg/mL, respectively. The candidate vaginal gels have the potential for a triggered release by the acid phosphatase enzyme present in the seminal fluid, thus, serving as a strategic point to prevent HIV transmission.