Short and long-term effect of polycarbophil vaginal gel on vaginal atrophy of peri- and post-menopausal women. The TRIPLE study.

OBJECTIVES: This TRIPLE study was aimed to evaluate the efficacy of polycarbophil vaginal gel (PCV) in treating symptoms of vaginal atrophy (VA) of peri- and post-menopausal women. MATERIALS AND METHODS: Sexually active women in peri- (n = 29) and post-menopause (n = 54) suffering from VA, were progressively enrolled and treated for 30 days with PCV. Those wishing to continue (n = 73) were treated for additional 180 days. PCV was administered as one application twice a week. The vaginal health index (VHI; range 5 to 25) and the visual analogue score (VAS range for 0 to 100 mm for each item) for vaginal dryness, irritation, and pain at intercourse, along with the global symptoms score (GSS; range 1 to 15) and treatment safety, were evaluated at baseline and after 30 days. In those continuing the treatment an evaluation was performed after additional 180 days. RESULTS: Women in peri and post-menopause were of 48.7 ± 3.3 years and 57.5 ± 5.7 years old., respectively. At baseline all outcomes were significantly worse (p<0.002) in postmenopausal group, except the VHI (p < 0.056). After 30 days VHI increased (p < 0.001) of 4.1 ± 0.5 (mean ± SE), and 5.1 ± 0.4 in peri- and post-menopausal women respectively. VAS of vaginal dryness decreased (p < 0.001) of -24.4 ± 3.6, and -52.7 ± 2.6 (p < 0.001), VAS of irritation decreased (p<0.001) of -18.6 ± 4.4 and -47.8 ± 3.2, VAS of pain decreased (p < 0.001) of -26.2 ± 4.3 and -55.6 ± 3.1 and the GSS decreased (p < 0.001) of -3.9 ± 0.3, and -4.9 ± 0.2, in peri and post-menopausal women, respectively. All the modifications were significantly greater (p < 0.001)(p < 0.032 for GSS) in postmenopausal women, and after 30 days all outcomes were similar in the two groups of women. In comparison to baseline, after 210 days of treatment VHI increased of 7.7 ± 0.3 (p < 0.001), VAS of vaginal dryness decreased of -53.6 ± 1.9 (p < 0.001) VAS of irritation of -42.6 ± 1.4 (p < 0.001) VAS of pain of -46.7 ± 2.3 (p < 0.001) and the GSS of -6.5 ± 0.2 ± 0.2 (p < 0.001). All outcomes improved (p < 0.001) over the values observed after 30 days of treatment (p < 0.001). No side effect was reported. CONCLUSIONS: In peri- and post-menopausal women PCV administration rapidly improves VA symptoms, and its prolongation up to 6 months further increases its efficacy.

Hypotonic, gel-forming delivery system for vaginal drug administration.

Vaginal drug delivery is often preferred over systemic delivery to reduce side effects and increase efficacy in treating diseases and conditions of the female reproductive tract (FRT). Current vaginal products have drawbacks, including spontaneous ejection of drug-eluting rings and unpleasant discharge from vaginal creams. Here, we describe the development and characterization of a hypotonic, gel-forming, Pluronic-based delivery system for vaginal drug administration. The rheological properties were characterized with and without common hydrogel polymers to demonstrate the versatility. Both qualitative and quantitative approaches were used to determine the Pluronic F127 concentration below the critical gel concentration (CGC) that was sufficient to achieve gelation when formulated to be hypotonic to the mouse vagina. The hypotonic, gel-forming formulation was found to form a thin, uniform gel layer along the vaginal epithelium in mice, in contrast to the rapidly forming conventional gelling formulation containing polymer above the CGC. When the hypotonic, gel-forming vehicle was formulated in combination with a progesterone nanosuspension (ProGel), equivalent efficacy was observed in the prevention of chemically-induced preterm birth (PTB) compared to commercial Crinone® vaginal cream. Further, ProGel showed marked benefits in reducing unpleasant discharge, reducing product-related toxicity, and improving compatibility with vaginal bacteria in vitro. A hypotonic, gel-forming delivery system may be a viable option for therapeutic delivery to the FRT.

Development and verification of mechanistic vaginal absorption and metabolism model to predict systemic exposure after vaginal ring and gel application.

AIMS: The current work describes the development of mechanistic vaginal absorption and metabolism model within Simcyp Simulator to predict systemic concentrations following vaginal application of ring and gel formulations. METHODS: Vaginal and cervix physiology parameters were incorporated in the model development. The study highlights the model assumptions including simulation results comparing systemic concentrations of 5 different compounds, namely, dapivirine, tenofovir, lidocaine, ethinylestradiol and etonogestrel, administered as vaginal ring or gel. Due to lack of data, the vaginal absorption parameters were calculated based on assumptions or optimized. The model uses release rate/in vitro release profiles with formulation characteristics to predict drug mass transfer across vaginal tissue into the systemic circulation. RESULTS: For lidocaine and tenofovir vaginal gel, the predicted to observed AUC0-t and Cmax ratios were well within 2-fold error limits. The average fold error (AFE) and absolute AFE indicating bias and precision of predictions range from 0.62 to 1.61. For dapivirine, the pharmacokinetic parameters are under and overpredicted in some studies due to lack of formulation composition details and relevance of release rate used in ring model. The predicted to observed AUC0-t and Cmax ratios were well within 2-fold error limits for etonogestrel and ethinylestradiol vaginal ring (AFEs and absolute AFEs from 0.84 to 1.83). CONCLUSION: The current study provides first of its kind physiologically based pharmacokinetic framework integrating physiology, population and formulation data to carry out in silico mechanistic vaginal absorption studies, with the potential for virtual bioequivalence assessment in the future.

Perioperative Vaginal Estrogen as Adjunct to Native Tissue Vaginal Apical Prolapse Repair: A Randomized Clinical Trial.

Importance: Surgical repairs of apical/uterovaginal prolapse are commonly performed using native tissue pelvic ligaments as the point of attachment for the vaginal cuff after a hysterectomy. Clinicians may recommend vaginal estrogen in an effort to reduce prolapse recurrence, but the effects of intravaginal estrogen on surgical prolapse management are uncertain. Objective: To compare the efficacy of perioperative vaginal estrogen vs placebo cream on prolapse recurrence following native tissue surgical prolapse repair. Design, Setting, and Participants: This randomized superiority clinical trial was conducted at 3 tertiary US clinical sites (Texas, Alabama, Rhode Island). Postmenopausal women (N = 206) with bothersome anterior and apical vaginal prolapse interested in surgical repair were enrolled in urogynecology clinics between December 2016 and February 2020. Interventions: The intervention was 1 g of conjugated estrogen cream (0.625 mg/g) or placebo, inserted vaginally nightly for 2 weeks and then twice weekly to complete at least 5 weeks of application preoperatively; this continued twice weekly for 12 months postoperatively. Participants underwent a vaginal hysterectomy (if uterus present) and standardized apical fixation (either uterosacral or sacrospinous ligament fixation). Main Outcomes and Measures: The primary outcome was time to failure of prolapse repair by 12 months after surgery defined by at least 1 of the following 3 outcomes: anatomical/objective prolapse of the anterior or posterior walls beyond the hymen or the apex descending more than one-third of the vaginal length, subjective vaginal bulge symptoms, or repeated prolapse treatment. Secondary outcomes included measures of urinary and sexual function, symptoms and signs of urogenital atrophy, and adverse events. Results: Of 206 postmenopausal women, 199 were randomized and 186 underwent surgery. The mean (SD) age of participants was 65 (6.7) years. The primary outcome was not significantly different for women receiving vaginal estrogen vs placebo through 12 months: 12-month failure incidence of 19% (n = 20) for vaginal estrogen vs 9% (n = 10) for placebo (adjusted hazard ratio, 1.97 [95% CI, 0.92-4.22]), with the anatomic recurrence component being most common, rather than vaginal bulge symptoms or prolapse repeated treatment. Masked surgeon assessment of vaginal tissue quality and estrogenization was significantly better in the vaginal estrogen group at the time of the operation. In the subset of participants with at least moderately bothersome vaginal atrophy symptoms at baseline (n = 109), the vaginal atrophy score for most bothersome symptom was significantly better at 12 months with vaginal estrogen. Conclusions and Relevance: Adjunctive perioperative vaginal estrogen application did not improve surgical success rates after native tissue transvaginal prolapse repair. Trial Registration: ClinicalTrials.gov Identifier: NCT02431897.

Results of a phase 1, randomized, placebo-controlled first-in-human trial of griffithsin formulated in a carrageenan vaginal gel.

HIV pre-exposure prophylaxis (PrEP) is dominated by clinical therapeutic antiretroviral (ARV) drugs. Griffithsin (GRFT) is a non-ARV lectin with potent anti-HIV activity. GRFT's preclinical safety, lack of systemic absorption after vaginal administration in animal studies, and lack of cross-resistance with existing ARV drugs prompted its development for topical HIV PrEP. We investigated safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of PC-6500 (0.1% GRFT in a carrageenan (CG) gel) in healthy women after vaginal administration. This randomized, placebo-controlled, parallel group, double-blind first-in-human phase 1 study enrolled healthy, HIV-negative, non-pregnant women aged 24-45 years. In the open label period, all participants (n = 7) received single dose of PC-6500. In the randomized period, participants (n = 13) were instructed to self-administer 14 doses of PC-6500 or its matching CG placebo (PC-535) once daily for 14 days. The primary outcomes were safety and PK after single dose, and then after 14 days of dosing. Exploratory outcomes were GRFT concentrations in cervicovaginal fluids, PD, inflammatory mediators and gene expression in ectocervical biopsies. This trial is registered with ClinicalTrials.gov, number NCT02875119. No significant adverse events were recorded in clinical or laboratory results or histopathological evaluations in cervicovaginal mucosa, and no anti-drug (GRFT) antibodies were detected in serum. No cervicovaginal proinflammatory responses and no changes in the ectocervical transcriptome were evident. Decreased levels of proinflammatory chemokines (CXCL8, CCL5 and CCL20) were observed. GRFT was not detected in plasma. GRFT and GRFT/CG in cervicovaginal lavage samples inhibited HIV and HPV, respectively, in vitro in a dose-dependent fashion. These data suggest GRFT formulated in a CG gel is a safe and promising on-demand multipurpose prevention technology product that warrants further investigation.

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.

Design aspects of vaginal applicators that influence acceptance among target users.

Although sensory-guided product design is most traditionally used by food and beverage companies, the approach has widespread application for many other products, including pharmaceuticals and medical devices. Previously, our team used sensory methods to explore preclinical optimization of soft-gel vaginal microbicides. Past clinical trials suggest vaginal microbicides may be an effective means for women to protect themselves from HIV and other sexually transmitted infections, but these microbicides will not work if they are not used due to poor acceptability. Our prior work suggests properties like firmness, size, and shape all influence women's willingness to try soft-gel vaginal suppositories. As product insertion is part of the overall experience of using vaginal microbicides, understanding the features of vaginal applicators that appeal to women, and incorporating these insights into vaginal drug delivery systems, may also improve user adherence. Despite widespread use of vaginal applicators, there is minimal public data on women's perceptions of and preferences for physical applicator features. Other work suggests women want vaginal applicators that are single use, pre-filled, made of plastic, and easy to use, store, and discard. Applicator attributes that may be important to women, such as length, color, or visual appeal, have not been investigated previously. The objective of this research was to understand what physical applicator attributes are appealing to women. Here, 18 commercially available applicators were evaluated by a convenience sample of women (n = 102) for overall liking and perceptions of various attributes (perceived length and width, ease-of-grip, expected ease-of-use, expected comfort inside the body, visual appeal, color liking, and environmental friendliness). Preference mapping using both liking data and attribute data showed attributes such as color, visual appeal, ease of grip, expected ease of use, and expected comfort inside the body drove higher liking ratings for applicators, while perceived length negatively affected liking. In general, plastic tampon applicators contained more positive features and were better liked relative to a cardboard tampon applicator or applicators for insertion of medicated gels or suppositories. Incorporating more desirable features into applicators meant for insertion of vaginal microbicides or other vaginal medications may improve the user experience, and possibly user adherence.

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.

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.

A single-arm clinical trial investigating the effectiveness of a non-hormonal, hyaluronic acid-based vaginal moisturizer in endometrial cancer survivors.

OBJECTIVE: To assess the efficacy of non-hormonal, hyaluronic acid (HLA)-based vaginal gel in improving vulvovaginal estrogen-deprivation symptoms in women with a history of endometrial cancer. METHODS: For this single-arm, prospective, longitudinal trial, we enrolled disease-free women with a history of endometrial cancer who underwent surgery (total hysterectomy) and postoperative radiation. Participants used HLA daily for the first 2 weeks, and then 3×/week until weeks 12-14; dosage was then increased to 5×/week for non-responders. Vulvovaginal symptoms and pH were assessed at 4 time points (baseline [T1]; 4-6 weeks [T2]; 12-14 weeks [T3]; 22-24 weeks [T4]) with clinical evaluation, the Vaginal Assessment Scale (VAS), Vulvar Assessment Scale (VuAS), Female Sexual Function Index (FSFI), and Menopausal Symptom Checklist (MSCL). RESULTS: Of 43 patients, mean age was 59 years (range, 38-78); 54% (23/43) were partnered; and 49% (21/43) were sexually active. VAS, VuAS, MSCL, and SAQ (Sexual Activity Questionnaire) scores significantly improved from baseline to each assessment point (all p < .002). FSFI total mean scores significantly increased from T1 to T2 (p < .05) and from T1 to T4 (p < .03). At T1, 41% (16/39) felt confident about future sexual activity compared to 68% (17/25) at T4 (p = .096). Severely elevated vaginal pH (>6.5) decreased from 30% (13/43) at T1 to 19% (5/26) at T4 (p = .41). CONCLUSION: The HLA-based gel improved vulvovaginal health and sexual function of endometrial cancer survivors in perceived symptoms and clinical exam outcomes. HLA administration 1-2×/week is recommended for women in natural menopause; a 3-5×/week schedule appears more effective for symptom relief in cancer survivors.

Labial adhesion in a postmenopausal female: A case report.

RATIONALE: Voiding difficulty is more common in males, although it is not uncommon in females. Female voiding difficulty can be caused by iatrogenic, anatomic, and neurogenic factors, and specifically urethra stricture, impaired detrusor contractility, primary bladder neck obstruction, and detrusor-external sphincter dyssynergia. Labial adhesion is a rare cause of female voiding difficulty.The incidence of labial fusion has been reported to be 0.6% to 1.4% in children; however, the incidence in the elderly has yet to be fully elucidated. PATIENT CONCERNS: We present the case of a postmenopausal and sexually inactive 76-year-old female patient who had nearly total vaginal and urethral occlusion due to labial adhesion. She had no underlying diseases and came to our clinic with a 10-month history of voiding difficulty, postmicturition dribbling, and involuntary urinary leakage when getting up. DIAGNOSIS: A genital examination revealed nearly total fusion of the labia minor with only a 3-mm pinhole opening at the posterior end. INTERVENTIONS: Treatment included surgical separation, the local application of estrogen cream, and self-dilatation. She also received an antimuscarinic agent to treat overactive bladder secondary to bladder outlet obstruction which was caused by labial adhesion. OUTCOMES: No surgical complications occurred. Moreover, no labial adhesion or voiding dysfunction was found immediately after the surgery or after 6 months of follow-up. LESSONS SUBSECTIONS: Genital examinations are a basic but very important noninvasive skill for physicians. This case report highlights that genital examinations should be a priority for patients with gynecological or urological symptoms.

Formulation, development, and in-vitro/ex-vivo evaluation of vaginal bioadhesive salbutamol sulfate tablets for preterm labor.

Preterm labor is the main cause of death and serious illness of both infants and pregnant women in Africa and worldwide. Parenteral and oral salbutamol sulfate as a B2 antagonist has been used for the treatment of preterm labor. The study aims are to formulate salbutamol sulfate non-invasive vaginal bioadhesive tablets to avoid the side effects of conventional formulations. Full factorial design 41 ×31 ×21 was used for the preparation of 24 vaginal bioadhesive tablet formulations. The independent factors were polymer type (Carbopol 934, HPMC 4000, HEC, and PEG 6000), polymer to drug ratio (1:1, 2:1, and 3:1), and diluent (lactose and mannitol). Vaginal bioadhesive tablets were evaluated for residence time and time required for release 50% of salbutamol sulfate T50% as dependent variables. The formulations were evaluated in terms of drug content, mass variation, hardness, friability, swelling index, residence time, and in-vitro drug release. Results revealed that polymer and diluent types are the most significant factors in both residence time and T50%. A strong positive correlation (0.91) between in-vitro and ex-vivo permeation was observed, which predict the best in-vivo performance of salbutamol vaginal bioadhesive tablet. Thus, salbutamol sulfate vaginal bioadhesive tablets could be a successful remedy for preterm labor.

Carrageenan-Based Acyclovir Mucoadhesive Vaginal Tablets for Prevention of Genital Herpes.

Women are the most affected by genital herpes, which is one of the most common sexually transmitted infections, affecting more than 400 million people worldwide. The application of vaginal microbicides could provide a safe method of protection. Acyclovir is a safe and effective medication for vaginal administration, and numerous benefits have been observed in the treatment of primary or recurrent lesions due to genital herpes. Vaginal tablets based on a combination of the polymers iota-carrageenan and hydroxypropyl methylcellulose were developed for the controlled release of acyclovir. Swelling, mucoadhesion and drug release studies were carried out in simulated vaginal fluid. The tablets, containing a combination of iota-carrageenan and hydroxypropyl methylcellulose, have an adequate uptake of the medium that allows them to develop the precise consistency and volume of gel for the controlled release of acyclovir. Its high mucoadhesive capacity also allows the formulation to remain in the vaginal area long enough to ensure the complete release of acyclovir. These promising formulations for the prevention of genital herpes deserve further evaluation.

The effect of oxytocin vaginal gel on vaginal atrophy in postmenopausal women: a randomized controlled trial.

BACKGROUND: Around 90% of postmenopausal women are suffering from vaginal atrophy. This study aimed to evaluate the effect of oxytocin vaginal gel on vaginal atrophy among postmenopausal women. METHODS: This was a randomized controlled trial that was conducted on 96 postmenopausal women who suffered from vaginal atrophy. The inclusion criteria were: literate women, age 40-60, at least 1 year passed from their last menstrual period or the level of FSH > 40 IU, monogamous women with the sexual relationship. Women in the intervention group, requested to use one applicator of 400 IU oxytocin gel per night and women in the placebo group used placebo each night. The subjective symptoms of vaginal atrophy, vaginal PH, maturation index were measured before and after the intervention. RESULTS: The number of superficial cells was increased significantly in the oxytocin group compared to placebo (38.7 ± 7.18 vs. 3.69 ± 2.76, p = 0.0001), while the number of parabasal cells was decreased significantly in the oxytocin compared to placebo after the intervention. The improvement of the maturation index was more dominant in the oxytocin group (increased from 7.76 ± 4.68 to 52.48 ± 7.54) in comparison to the placebo group (increased from 8.58 ± 4.35 to 13.25 ± 5.06). The PH of the vagina decreased significantly in the oxytocin group in comparison to the placebo group (p = 0.0001). After 8 weeks, 88.6 and 7.1% of women in the oxytocin and placebo groups did not show the severe symptoms of vaginal atrophy (p = 0.001). CONCLUSION: The results of this study showed that eight- week intervention with oxytocin vaginal gel (400 IU) could significantly improve the vaginal maturation index, subjective symptoms of vaginal atrophy and reduce the PH of the vagina. Using this medication in women who have a contraindication for hormone therapy is recommended. TRIAL REGISTRATION: IRCT20160602028220N2.

Glycine Max (L.) Merr isoflavone gel improves vaginal vascularization in postmenopausal women.

Objective: This study aimed to analyze the effects of isoflavones from Glycine max (L.) Merr (soy) used topically as a vaginal gel on the induction of vascularization of the vaginal tissue in postmenopausal women.Study design: A placebo-controlled, randomized, double-blind trial was conducted with 22 postmenopausal women, randomly allocated for treatment with Glycine max (L.) Merr isoflavone 4% vaginal gel daily for 12 weeks or with placebo gel for the same period.Main outcome measure: Vaginal microbiopsies were collected before and after the 12-week treatment. Immunohistochemistry analyses were performed to provide a blood vessel count per field in the vaginal tissue, pre and post intervention.Results: The isoflavone group exhibited a significant increase in blood vessels per field relative to baseline, whereas the placebo group showed no difference compared to baseline. There was a significant difference in the increase of the number of blood vessels between the isoflavone and placebo groups.Conclusion: The results showed that local administration of Glycine max (L.) Merr isoflavone gel promoted a significant improvement in the number of blood vessels in the vaginal tissue of postmenopausal women.

Does hysterosalpingo-foam sonography have any therapeutic effect? A systematic review.

INTRODUCTION: Tubal patency is one of the mandatory and necessary conditions to be granted in order to guarantee a good pregnancy rate. Numerous studies have been conducted to compare the various testing techniques for tubal evaluation in order to optimize the diagnostic-therapeutic process. Aim of this review is to clarify if hysterosalpingo-foam sonography could be considered as a useful tool not only in the diagnostic procedure, but also in treatment of infertility. EVIDENCE ACQUISITION: We performed a comprehensive search of relevant studies from January 2010 to December 2019 to ensure all possible studies were captured. A systematic search of PubMed databases was conducted. EVIDENCE SYNTHESIS: Over the years, increasingly less invasive approaches have been used to test tubal patency. For many years Laparoscopic with chromopertubation (DLS) has been considered the reference standard, then less invasive procedures have been introduced, such as hysterosalpingography (HSG). Sonohysterosalpingography (HyCoSy) represents a non-invasive procedure with accuracy comparable to HSG. Several studies have been made on different contrast agents that could be used on this procedure and recent studies considered hysterosalpingo-foam sonography (HyFoSy) procedure as a new technique used for the study of tubal function performed on unfertile women. Nowadays, HyFoSy is largely used in the study of tubal patency, but it is not completely clear the role of this technique as treatment of imperviousness of Fallopian tubes, leading to an increase in pregnancy rate after its use. CONCLUSIONS: As described in the literature for other procedures, similarly with HyFoSy, the tubal flushing improves the chance of an embryo implanting and establishing a spontaneous pregnancy. More prospective studies should be taken to better analyze the singular maternal risk fators, hoping to offer more complete indications to recommend HyFoSy.

Analysis and new contraception frontiers with combined vaginal rings.

Combined vaginal rings (ethinylestradiol (EE)/desogestrel), indicated for contraception, are highly effective, comparable to other combined hormonal contraceptives, such as pills. In addition to this benefit, vaginal rings are easy to use, with a probable lower risk of forgetting, due to their non-daily, monthly schedule. Besides, for users with poor gastric tolerance to oral formulations, they represent a method with safety and comparable extraconceptive benefits. The latest generation rings have a novel polymeric structure, do not need special storage methods and do not generate accelerated initial release of EE, reducing the early increased systemic exposure to the synthetic steroids they contain. This review describes main aspects related to its use, efficacy, and safety for contraceptive purposes.

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.