Synthesis, characterization, and evaluation of BDDE crosslinked chitosan-TGA hydrogel encapsulated with genistein for vaginal atrophy.

Vagina atrophy is a common symptom in women after menopause owing to decreasing estrogen levels. The most conventional treatment for this condition is estrogen cream. The shortcoming is its weak adhesion to the vagina mucus, thus requiring frequent daily application. In this study, BDDE was selected to crosslink and graft chitosan with thioglycolic acid, to form thiolated chitosan (CT) and improve the mucoadhesive properties of chitosan. Genistein was selected as the bioactive molecule that could exhibit estrogen-like properties for long-term treatment of vaginal atrophy. The efficacies of the materials were characterized and evaluated both in vitro and in vivo. Results showed that the mucoadhesive property of CT was approximately two-fold stronger against the constant flow than unmodified chitosan. CT with genistein (CT-G) was administered intravaginally every three days in vivo. It showed that the developed CT-G recover 54 % of the epithelium thickness of an atrophic vagina and ease vaginal atrophy.

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.

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

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

Effectiveness of nonhormonal products for the treatment of women with vaginal atrophy / Efectividad de productos no hormonales para el tratamiento de las mujeres con atrofia vaginal

Objective: To describe the clinical progress of women with vaginal atrophy who receive nonhormonal treatment. Material and methods: Single-center retrospective longitudinal observational descriptive study in postmenopausal women aged 45-60 years with symptoms of vaginal atrophy who required nonhormonal treatment. Results: We included 98 women with a mean (SD) age of 54.6 (3.2) years and a mean time of 5.6 (3.0) years without menstrual periods. Of these, 63.3% were treated with hyaluronic acid and Centella asiatica cell lysate and the other 36.7% with glycerin and polycarbophil. The vaginal maturation index improved significantly after 3 months of treatment with hyaluronic acid and Centella asiatica: the parabasal cell count declined (-8.4%; 95%CI, -10.6 to -6.2; p=0.001) and the intermediate cell count increased (3.6%; 95%CI, 2.0-5.3; p=0.001), as did that of superficial cells (4.8%; 95%CI, 3.8-5.7; p=0.001). In addition, all symptoms and signs of vaginal atrophy improved after 3 months with treatment with hyaluronic acid and Centella asiatica lysate. There was no significant change in the vaginal maturation index or in symptoms and signs after 3 months of treatment with glycerin and polycarbophil. Conclusions: Three months of nonhormonal treatment with hyaluronic acid and Centella asiatica lysate significantly improved the vaginal maturation index

Objetivo: describir la evolución clínica de mujeres con atrofia vaginal que reciben un tratamiento no hormonal.Material y métodos:estudio descriptivo observacional retrospectivo longitudinal unicéntrico en mujeres posmenopáusicas de 45 a 60 años con síntomas de atrofia vaginal que hubieran requerido tratamiento no hormonal. Resultados: se incluyeron 98 mujeres con una edad media de 54,6 ± 3,2 años y un tiempo medio sin menstruación de 5,6 ± 3,0 años. El 63,3% de las mujeres eran tratadas con ácido hialurónico y lisado celular de centella asiática y el 36,7% con glicerol y policarbofil. El índice de maduración vaginal fue significativamente mejor tras tres meses de tratamiento con ácido hialurónico y lisado de centella asiática: descienden las células parabasales (-8,4%, IC95% (-10,6 - -6,2), p=0,001) y aumentan las intermedias (3,6%, IC95% (2,0 - 5,3), p=0,001) y las superficiales (4,8%, IC95% (3,8 - 5,7), p=0,001). Además, se redujeron todos los síntomas y signos de atrofia vaginal tras 3 meses con el tratamiento con ácido hialurónico y lisado de centella asiática. No se encontraron cambios tras tres meses de tratamiento con glicerol y policarbofil en el índice de maduración vaginal y de los síntomas y signos. Conclusiones: El tratamiento no hormonal con ácido hialurónico y lisado de centella asiática mejora significativamente el índice de maduración vaginal y los síntomas y signos de atrofia vaginal tras tres meses de tratamiento

Application of conjugated estrogen cream in the treatment of postmenopausal atrophic vaginitis.

To observe and analyze the effect of conjugated estrogen cream in the treatment of postmenopausal atrophic vaginitis. The 160 patients clearly diagnosed with postmenopausal atrophic vaginitis and treated in our hospital were selected as subjects and divided into study group and reference group with equal number of cases. The reference group was treated with compound metronidazole suppository, while the study group was treated with conjugated estrogen cream. The treatment efficacy of the two groups was compared and observed. Comparison of estradiol and folliclestimulating hormone levels after treatment in the two groups show that the study group has obvious advantage over the reference group, p<0.05; comparison of vagina cleanliness in the two groups after treatment shows the study group is significantly superior to the reference group, p<0.05; comparison of incidence of adverse reactions in the two groups shows that the study group has lower incidence, with statistical significance in comparison between the groups, p<0.05. Treatment of postmenopausal atrophic vaginitis with combination of conjugated estrogen cream and compound metronidazole suppository can achieve good results with high safety and reliability.

17ß-estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis.

OBJECTIVES: The efficacy and safety of 25-µg 17ß-estradiol vaginal tablets (Vagifem) were assessed and compared with 1.25-mg conjugated equine estrogen vaginal cream (Premarin Vaginal Cream) for the relief of menopausal-derived atrophic vaginitis, resulting from estrogen deficiency. DESIGN: In a multicenter, open-label, randomized, parallel-group study, 159 menopausal women were treated for 24 weeks with either vaginal tablets or vaginal cream. Efficacy was evaluated by relief of vaginal symptoms and concentrations of serum estradiol and follicle-stimulating hormone. Safety was monitored by the incidence of adverse events, evaluation of endometrial biopsies, and clinical laboratory results. Patients also assessed the acceptability of the study medications. RESULTS: Composite scores of vaginal symptoms (dryness, soreness, and irritation) demonstrated that both treatments provided equivalent relief of the symptoms of atrophic vaginitis. At weeks 2, 12, and 24, increases in serum estradiol concentrations and suppression of follicle-stimulating hormone were observed in significantly more patients who were using the vaginal cream than in those who were using the vaginal tablets (p < 0.001). Fewer patients who were using the vaginal tablets experienced endometrial proliferation or hyperplasia compared with patients who were using the vaginal cream. Significantly more patients who were using the vaginal tablets rated their medication favorably than did patients who were using the vaginal cream (p ≤ 0.001). Patients who were receiving the vaginal tablets also had a lower incidence of patient withdrawal (10% versus 32%). CONCLUSIONS: Treatment regimens with 25-µg 17ß-estradiol vaginal tablets and with 1.25-mg conjugated equine estrogen vaginal cream were equivalent in relieving symptoms of atrophic vaginitis. The vaginal tablets demonstrated a localized effect without appreciable systemic estradiol increases or estrogenic side effects. Vaginal tablet therapy resulted in greater patient acceptance and lower withdrawal rates compared with vaginal cream therapy.

Prevention of recurrent lower urinary tract infections in postmenopausal women with genitourinary syndrome: outcome after 6 months of treatment with ospemifene.

Aim of this study was to evaluate the efficacy of ospemifene in the prevention of recurrent lower urinary tract infections in postmenopausal women with vulvovaginal atrophy. The study have a retrospective design. Thirty-nine patients were enrolled. Patients underwent clinical examination and urine culture. The urinary symptoms and the quality of life were evaluated with UTISA score, PUF and SF-36 questionnaires before and after treatment. All 39 patients received ospemifene 60 mg one tablet/daily for 6 months. Adverse effects and complications were assessed. Thirty-nine patients were enrolled in the study. Two patients experienced one new UTI episode and the mean number of positive urine culture decreased significantly after 6 months (3.65 ± 2.12 vs 0.25 ± 0.17, p < .0001). The mean number of urinary infection symptoms decreased significantly after treatment; dysuria reduced (4.76 ± 2.45 vs 0.89 ± 1.12). PUF score and SF-36 showed a statistically significant change (22.43 ± 5.89 vs 12.14 ± 3.21) and (52.86 ± 9.21 vs 83.43 ± 10.76). No adverse effects were reported and the total success rate was the 92.3% after 6 months at PGI-I. Ospemifene is a valid alternative with excellent tolerability for the UTIS prevention in postmenopausal patients.

Chitosan Ascorbate Nanoparticles for the Vaginal Delivery of Antibiotic Drugs in Atrophic Vaginitis.

The aim of the present work was the development of chitosan ascorbate nanoparticles (CSA NPs) loaded into a fast-dissolving matrix for the delivery of antibiotic drugs in the treatment of atrophic vaginitis. CSA NPs loaded with amoxicillin trihydrate (AX) were obtained by ionotropic gelation in the presence of pentasodium tripolyphosphate (TPP). Different CSA:TPP and CSA:AX weight ratios were considered and their influence on the particle size, polydispersion index and production yield were investigated. CSA NPs were characterized for mucoadhesive, wound healing and antimicrobial properties. Subsequently, CSA NPs were loaded in polymeric matrices, whose composition was optimized using a DoE (Design of Experiments) approach (simplex centroid design). Matrices were obtained by freeze-drying aqueous solutions of three hydrophilic excipients, polyvinylpirrolidone, mannitol and glycin. They should possess a mechanical resistance suitable for the administration into the vaginal cavity and should readily dissolve in the vaginal fluid. In addition to antioxidant properties, due to the presence of ascorbic acid, CSA NPs showed in vitro mucoadhesive, wound healing and antimicrobial properties. In particular, nanoparticles were characterized by an improved antimicrobial activity with respect to a chitosan solution, prepared at the same concentration. The optimized matrix was characterized by mechanical resistance and by the fast release in simulated vaginal fluid of nanoparticles characterized by unchanged size.

Vitamin D Proliferates Vaginal Epithelium through RhoA Expression in Postmenopausal Atrophic Vagina tissue.

Postmenopausal atrophic vagina (PAV) is the thinning of the walls of the vagina and decreased lugae of the vagina. PAV is caused by decreased estrogen levels in postmenopausal women. However, the harmful effects of hormone replacement therapy (HRT) have resulted in considerable caution in its use. Various estrogen agonist treatment options are available. Vitamin D is influences the regulation of differentiation and proliferation of various cells, especially tissues lining stratified squamous epithelium, such as the vaginal epithelium. In this study, we hypothesized that vitamin D could provide an alternative and a safe treatment option for PAV by promoting the proliferation and differentiation of the vaginal epithelium. Thirty six patients were enrolled in this case-control study. Vitamin D associated proteins in a vitamin D and sex hormone treated vaginal epithelial cell line as well as normal and PAV tissues were measured. To confirm of cell-to-cell junction protein expression, cell line and tissue studies included RT-PCR, immunohistochemistry staining, and immunoblot analyses. The expression of cell-to-cell junction proteins was higher in women with symptoms of atrophic vagina tissue compared to women without the symptoms. Vitamin D stimulated the proliferation of the vaginal epithelium by activating p-RhoA and Erzin through the vitamin D receptor (VDR). The results suggest that vitamin D positively regulates cell-to-cell junction by increasing the VDR/p-RhoA/p-Ezrin pathway. This is the first study to verify the relationship of the expression of RhoA and Ezrin proteins in vaginal tissue of PAV.

Lower urinary tract infections in women.

In her lifetime, a woman is highly likely to develop at least one lower urinary tract infection. Early detection and treatment are key. Being aware of predisposing factors for infection and understanding appropriate diagnosis and treatment regimens will help nurses in both primary and acute care manage these patients correctly. This will not only benefit patients but will also help prevent incorrect antimicrobial management and avoid unplanned admissions. This aim of this article is to provide nurses with the information they need to best advise both colleagues and patients on how to manage lower urinary tract infections in women.

A Dermatologist's Approach to Genitourinary Syndrome of Menopause.

BACKGROUND: Genitourinary syndrome of menopause (GSM) is a debilitating condition caused by hypoestrogenism that presents with vaginal dryness and dyspareunia as well as other genital, sexual, and urinary symptoms. Previously known as atrophic vaginitis, the term GSM is now used. OBJECTIVE: To help familiarise dermatologists with diagnosing and managing GSM. METHODS: In total, 218 articles were identified and reviewed by 2 independent authors using PubMed. Articles included were from December 2005 to December 2015. Sixty-seven articles met our inclusion criteria. RESULTS: GSM is a clinical diagnosis, requiring the presence of symptoms that should be bothersome and not accounted for by another condition. A pH test may help with diagnosis as vaginal pH will be increased from acidic to neutral. The Papanicolaou test is not recommended because of poor clinical correlation. First-line treatment is low-dose local vaginal estrogen therapy, which has proven efficacy and safety. Serum estrogen levels are not significantly affected with the exception of creams containing high-dose conjugated equine estrogens. Other options have yet to be approved for use in Canada but show promise. CONCLUSION: GSM is a debilitating and common condition that suffers from barriers to diagnosis and treatment. Current treatments are well tolerated, rewarding, and effective with rapid onset.

Efficacy of an orally administered combination of hyaluronic acid, chondroitin sulfate, curcumin and quercetin for the prevention of recurrent urinary tract infections in postmenopausal women.

OBJECTIVE: To assess whether the orally administered combination of hyaluronic acid (HA), chondroitin sulfate (CS), curcumin and quercetin could be effective in preventing recurrent cystitis in postmenopausal women and whether its efficacy was conditioned by the concurrent use of local estrogen therapy. STUDY DESIGN: This was a prospective evaluation of 145 postmenopausal women consecutively recruited from the database of three different investigators. All women should have mild-to-moderate urogenital atrophy and a history of recurrent urinary tract infections (≥2 episodes within 6 months or ≥3 episodes within 12 months documented by positive urine cultures) during the last year. Patients were assigned to three different therapeutic regimens: the first group was treated only with vaginal estrogens, the second group only with HA, CS, curcumin and quercetin per os, and the third group was treated with HA, CS, curcumin and quercetin associated with local estrogens. We evaluated the number of patients with <2 infective episodes in the 6-month follow-up and <3 episodes in the 12-month follow-up (main aim definition) and the reduction of related symptoms through a Visual Analog Scale (VAS) and the Pelvic Pain and Urgency/Frequency (PUF) patient symptom scale. Student's t-test and chi-squared test were used for data analysis as appropriate. RESULTS: At 6-month follow up, the main aim rate was 8%, 11.1% and 25% in the three groups, respectively (p<0.05 compared to baseline only in group 3). Although the reduction in the number of recurrent episodes became significant in all groups at 1 year follow-up, the main aim rate was almost double in women receiving both local estrogens and oral therapy (group 3) compared to those receiving single treatments. The improvement of related symptoms was significant in all groups at 12-month follow-up. CONCLUSIONS: In postmenopausal women, the combination of HA, CS, curcumin and quercetin per os was effective in preventing recurrent urinary tract infections, especially if administered with vaginal estrogen therapy.

Papel de ospemifeno en el tratamiento de la atrofia vulvovaginal en la mujer posmenopáusica / Role of ospemifene in the treatment of vulvar and vaginal atrophy in postmenopausal woman

A pesar de que los síntomas de atrofia vulvovaginal (AVV) tienen un impacto significativo en la vida de una mujer, el grado de insatisfacción con las terapias disponibles es elevado. Si además consideramos que muchas mujeres son reacias a aceptar los tratamientos vaginales o no pueden utilizarlos, se hace patente la necesidad médica no cubierta en el manejo de la AVV. Ospemifeno es el primer tratamiento oral que no contiene hormonas indicado para mujeres posmenopáusicas con AVV no candidatas a estrógenos locales, y el único modulador selectivo de los receptores estrogénicos (SERM) con actividad antagonista en la mama, neutral en el útero y agonista en los huesos y vagina. Ospemifeno restaura el epitelio vaginal mejorando significativamente los síntomas de sequedad vaginal y dispareunia, y la salud sexual. Además de un óptimo tratamiento, los profesionales deberían abordar proactivamente la salud vaginal como parte del cuidado de la mujer posmenopáusica, especialmente a la luz del escaso conocimiento que muestran las mujeres acerca de esta condición (AU)

Despite symptoms of vulvar and vaginal atrophy (VVA) can have a significant impact on a woman’s life, the level of dissatisfaction with available VVA treatments is high. If we also consider that many women are reluctant to accept vaginal treatments or are unable to use it, the unmet medical need in the management of VVA becomes evident. Ospemifene is the first oral treatment that does not contain hormones, for post-menopausal women with VVA who are not candidates for local estrogens, and the only SERM with antagonistic effect in breast, neutral in uterus, and agonistic in bone and vagina. Ospemifene restores the vaginal epithelium and show significant improvements in symptoms of vaginal dryness and dyspareunia and therefore in the woman’s sexual function. Besides an optimal treatment, professionals should proactively address the vaginal health as part of postmenopausal women care, particularly in view of survey results highlighting the poor understanding of this condition that women have (AU)

Vaginal estrogen products in hormone receptor-positive breast cancer patients on aromatase inhibitor therapy.

Atrophic vaginitis represents a major barrier to compliance with aromatase inhibitor (AI) therapy in breast cancer (BC) survivors. While local estrogen therapy is effective for postmenopausal vaginal dryness, the efficacy of such therapies has not been evaluated systematically in hormone receptor-positive (HR+) BC patients on AI therapy. Furthermore, the potential risk of breast cancer recurrence with vaginal estrogen therapy represents a long-term safety concern for the patients with HR + BC. Unfortunately, there is no standardized assay to measure very low concentrations of estradiol (E2) in these women being treated with AI therapy. This makes it difficult to evaluate even indirectly the potential risk of BC recurrence with vaginal estrogen therapy in HR + BC patients on AI therapy. In this review, we describe available assays to measure very low concentrations of E2, discuss the Food and Drug Administration-approved vaginal estrogen products on the market, and summarize published and ongoing clinical trials evaluating the safety and efficacy of vaginal estrogen in HR + BC patients on AI therapy. In the absence of any randomized controlled clinical trials, this review serves as a summary of available clinical data and ongoing studies to aid clinicians in selecting the best available option for their patients.

Vaginal estrogen for genitourinary syndrome of menopause: a systematic review.

OBJECTIVE: To comprehensively review and critically assess the literature on vaginal estrogen and its alternatives for women with genitourinary syndrome of menopause and to provide clinical practice guidelines. DATA SOURCES: MEDLINE and Cochrane databases were searched from inception to April 2013. We included randomized controlled trials and prospective comparative studies. Interventions and comparators included all commercially available vaginal estrogen products. Placebo, no treatment, systemic estrogen (all routes), and nonhormonal moisturizers and lubricants were included as comparators. METHODS OF STUDY SELECTION: We double-screened 1,805 abstracts, identifying 44 eligible studies. Discrepancies were adjudicated by a third reviewer. Studies were individually and collectively assessed for methodologic quality and strength of evidence. TABULATION, INTEGRATION, AND RESULTS: Studies were extracted for participant, intervention, comparator, and outcomes data, including patient-reported atrophy symptoms (eg, vaginal dryness, dyspareunia, dysuria, urgency, frequency, recurrent urinary tract infection (UTI), and urinary incontinence), objective signs of atrophy, urodynamic measures, endometrial effects, serum estradiol changes, and adverse events. Compared with placebo, vaginal estrogens improved dryness, dyspareunia, urinary urgency, frequency, and stress urinary incontinence (SUI) and urgency urinary incontinence (UUI). Urinary tract infection rates decreased. The various estrogen preparations had similar efficacy and safety; serum estradiol levels remained within postmenopausal norms for all except high-dose conjugated equine estrogen cream. Endometrial hyperplasia and adenocarcinoma were extremely rare among those receiving vaginal estrogen. Comparing vaginal estrogen with nonhormonal moisturizers, patients with two or more symptoms of vulvovaginal atrophy were substantially more improved using vaginal estrogens, but those with one or minor complaints had similar symptom resolution with either estrogen or nonhormonal moisturizer. CONCLUSION: All commercially available vaginal estrogens effectively relieve common vulvovaginal atrophy-related complaints and have additional utility in patients with urinary urgency, frequency or nocturia, SUI and UUI, and recurrent UTIs. Nonhormonal moisturizers are a beneficial alternative for those with few or minor atrophy-related symptoms and in patients at risk for estrogen-related neoplasia. CLINICAL TRIAL REGISTRATION: PROSPERO International prospective register of systematic reviews, http://www.crd.york.ac.uk/PROSPERO/, CRD42013006656.